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315 Study Matches

Phase 2 Study of DKN-01 in Colorectal Cancer (DeFianCe)

This is a Phase 2 randomized, open-label, two-part, multicenter study with a safety run-in to evaluate efficacy and safety of DKN-01 plus FOLFIRI/FOLFOX and bevacizumab versus standard of care (SOC) [FOLFIRI/FOLFOX and bevacizumab] as second-line treatment of advanced CRC patients.
Dustin Deming, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05480306
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Adult patients with advanced CRC with measurable disease (RECIST v1.1) who have radiographically progressed during or following one line of systemic treatment will be enrolled in the study.
Inclusion Criteria:
Patients meeting all of the following criteria will be considered eligible for study entry: 1. Disease progression following first-line systemic therapy with any fluoropyrimidine-based regimen for advanced disease (except FOLFOXIRI, see exclusion criteria). • Patients may have received prior neoadjuvant or adjuvant therapy which could have included irinotecan or oxaliplatin. If progression has occurred within 12 months from last dose of neoadjuvant or adjuvant treatment, this regimen will be considered as the one line of systemic therapy for advanced disease.
• If assigned to receive FOLFIRI, patient may have received no prior irinotecan as part of first-line systemic therapy.
• If assigned to receive FOLFOX, patient may have received no prior oxaliplatin as part of first line systemic therapy.
• Prior treatment with an anti-VEGF or anti-EGFR therapy is allowed as first-line and/or maintenance systemic therapy. 2. Able to provide written informed consent for any study specific procedures. 3. One or more tumors measurable on radiographic imaging as defined by RECIST 1.1 4. Sufficient tumor tissue for mandatory pre-treatment evaluation (fresh biopsy [preferred], or archived tissue block specimen). 5. ECOG performance status ≤1 within 7 days of first dose of study drug. Acceptable liver, renal, hematologic, and coagulation function 6. Females of childbearing potential and male partners of female patients must agree to use adequate contraception during the study and for 6 months after their last dose of study drug
Exclusion Criteria:
Patients meeting any of the following criteria are not eligible for study entry: 1. Diagnosis of Microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) and/or BRAF V600E mutation positive colorectal cancer. 2. Prior therapy with an anti-DKK1, FOLFOXIRI, PD-1, anti-PD-L1, anti-PD-L-2 or any other antibody or drug specifically targeting T-cell co-stimulation or coinhibitory checkpoint. 3. Systemic anti-cancer therapy within 28 days prior to first dose of study drug. 4. Major surgery within 28 days prior to first dose of study drug. 5. Prior radiation therapy within 14 days prior to first dose of study drug. 6. Active leptomeningeal disease or uncontrolled brain metastases. 7. Any active cancer ≤ 2 years before first dose of study drug with the exception of cancer for this study. 8. New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months, or unstable arrhythmia. 9. Fridericia-corrected QT interval (QTcF) > 470 msec (female) or history of congenital long QT syndrome. 10. Active, uncontrolled bacterial, viral, or fungal infections, within 14 days of study entry requiring systemic therapy. 11. Serious nonmalignant disease 12. Pregnant or nursing. 13. History of osteonecrosis of the hip or have evidence of structural bone abnormalities in the proximal femur on MRI scan that are symptomatic and clinically significant. 14. Known osteoblastic bony metastasis. 15. Major surgery 28 days prior to study entry. 16. Prior radiation therapy within 14 days prior to study entry. 17. Significant allergy to a pharmaceutical therapy that, in the opinion of the Investigator, poses an increased risk to the patient. 18. Active substance abuse. 19. Known dihydropyrimidine dehydrogenase deficiency. 20. Administration of a live vaccine within 28 days before first dose of study drug
Colorectal Cancer, Colorectal Adenocarcinoma, Colo-rectal Cancer, Colorectal Cancer Metastatic, Colon, Rectum, Colon and Rectum
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Randomized Therapy In Status Epilepticus (RAISE)

This study will evaluate the effectiveness and safety of an investigational product (IP), intravenous (IV) ganaxolone, to treat participants with status epilepticus (SE).
Aaron Struck, Medical Student
All
12 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04391569
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Inclusion Criteria:
1. Participant, participant's parent, guardian, or legal authorized representative (LAR) must provide signed of informed consent/assent, and once capable (per institution guidelines), there must be documentation of consent/assent by the participant demonstrating they are willing and aware of the investigational nature of the study and related procedures. Where allowed by law, where the participant lacks the capacity to make informed decisions regarding his/her medical treatment options, the treating clinician may follow their deferred consenting practices. The clinician will make the final decision based on the best interests of the particiapant. 2. Male or females 12 years of age and older at the time of the first dose of IP 3. SE meeting the following criteria: a. A diagnosis of SE with or without prominent motor features based on clinical and EEG findings: i. Diagnosis is established by:
• For SE with prominent motor features: Clinical and EEG seizure activity indicative of convulsive, myoclonic or focal motor SE.
• For SE without prominent motor features (nonconvulsive SE): Appropriate clinical features and an EEG indicative of non-convulsive status epilepticus (NCSE) ii. For any type of SE:
• At least 6 minutes of cumulative seizure activity over a 30-minute period within the hour before IP initiation, AND
• Seizure activity during the 30 minutes immediately prior to IP initiation b. The treating clinician(s) anticipate that IV anesthesia is likely to be the next treatment for SE that persists following initiation of IP 4. Participants must have received any two or more of the following agents for treatment of the current episode of SE administered at an adequate dose and for a sufficient duration, in the judgment of the investigator, to demonstrate efficacy
• Benzodiazepines,
• IV Fosphenytoin/phenytoin,
• IV Valproic acid,
• IV Levetiracetam,
• IV Lacosamide,
• IV Brivaracetam, or
• IV Phenobarbital 5. Body mass index (BMI) < 40 or, if BMI is not able to be calculated at screening, participant is assessed by investigator as not morbidly obese
Exclusion Criteria:
1. Life expectancy of less than 24 hours 2. Anoxic brain injury or an uncorrected rapidly reversable metabolic condition as the primary cause of SE (e.g., hypoglycemia < 50 milligram per deciliter [mg/dL] or hyperglycemia > 400 mg/dL) 3. Participants who have received high-dose IV anesthetics (e.g., midazolam, propofol, thiopental, or pentobarbital) during the current episode of SE for more than 18 hours, or who continue to have clinical or electrographic evidence of persistent seizures while receiving high-dose IV anesthetics. 4. Clinical condition or advance directive that would NOT permit use of IV anesthesia 5. Participants known or suspected to be pregnant 6. Participants with known allergy or sensitivity to progesterone or allopregnanolone medications/supplements 7. Receiving a concomitant IV product containing Captisol® 8. Known or suspected hepatic insufficiency or hepatic failure leading to impaired synthetic liver function. 9. Known or suspected stage 3B (moderate to severe; estimated glomerular filtration rate [eGFR] 44-30 milliliter/minutes/1.73-meter square [mL/min/1.73m^2]), stage 4 (severe; eGFR 29-15 mL/min/1.73m^2), or stage 5 (kidney failure; eGFR < 15 mL/min/1.73m^2 or dialysis) kidney disease 10. Use of an investigational product for which less than 30 days or 5 half-lives have elapsed from the final product administration. Participation in a non-interventional clinical study does not exclude eligibility.
Status Epilepticus, Other
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EPPIC-Net: Platform Protocol to Assess Treatments for Painful Diabetic Peripheral Neuropathy

This is a Platform Protocol to perform Phase II clinical trials in The Early Phase Pain Investigation Clinical Network (EPPIC-Net), under The Helping to End Addiction Long-termSM Initiative, or NIH HEAL InitiativeSM, related to the treatment of Painful Diabetic Peripheral Neuropathy (PDPN) in a platform setting to test multiple assets under a single protocol.
Nalini Sehgal
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05476276
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Inclusion Criteria:
1. Able to provide informed consent. Legally Authorized Representatives (LARs) will not be permitted. 2. 18 years of age and older 3. Diagnosis of diabetes mellitus 4. Meets the Toronto Criteria for probable clinical sensorimotor polyneuropathy, with PDPN symptoms present for at least six months. This is defined as a combination of symptoms and signs with any two or more of the following (must be present bilaterally in the distal lower extremities): neuropathic symptoms, decreased distal sensation, or unequivocally decreased (or absent) ankle reflexes. Specifically: a. The presence of any neuropathic symptoms on either the "Douleur Neuropathique en 4 Questions" (DN4) or the EPPIC-Net Neuropathy Exam will suffice to demonstrate "neuropathic symptoms." b. Decreased distal sensation is satisfied by any of the following: i. "Yes" is checked at least once under Question 3 of the DN4 which queries hypoesthesia to touch and pinprick. ii. At least one score of "reduced" or "absent" on the right AND at least one score of "reduced" or "absent" on the left in any of the following items from the EPPIC-Net Neuropathy Exam:
• Pin sensation in segments 1 or 2 (i.e. the toes and feet)
• Vibration at the great toe
• Joint position at the great toe
• Light touch/touch pressure at the great toe
• Temperature at the great toe
• Monofilament at the great toe c. Decreased or absent ankle reflexes is satisfied by a score of "reduced" or "absent" on the right AND left in the "Ankle reflex" item in the EPPIC-Net Neuropathy Exam. 5. A score of at least 4 on the "Douleur Neuropathique en 4 Questions" (DN4). 6. Pain reporting during a pre-defined 7-day screening period meets study criteria (to be established using a centrally-administered screening algorithm) which may account for mean pain intensity reported, variability in reported values, and adherence in reporting. 7. Patient reported daily 11-point NRS (for average and worst pain over the last 24 hours) is completed on at least 5 out of the 7 days in the baseline period. 8. Participants must be willing and able to comply with scheduled visits, the treatment schedule, laboratory testing, and other requirements of the study (e.g., completion of app-based daily reporting). 9. Females may be included if they meet at least one of the following criteria (note that individual ISAs may specify more stringent measures to prevent pregnancy): a. Are not of childbearing potential, defined as one or more of the following: i. Post-menopausal for at least 1 year ii. Surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) iii. XY genotype iv. Turner syndrome v. Uterine agenesis. b. Are completely abstinent from sexual activity capable of resulting in pregnancy (as part of their preferred and usual lifestyle). This will include females whose sole sexual partner is a male who has undergone surgical sterilization or vasectomy. c. Women of childbearing potential will agree to practice an effective form of two types of birth control, which are defined as those, alone or in combination, that result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly. This must be done before, throughout, and for 30 days after the last dose of study drug. Acceptable methods are: i. Hormonal methods such as the vaginal ring, or oral, implantable, injectable, or transdermal contraceptives for a minimum of 1 full cycle (based on the participant's usual menstrual cycle period) before study drug administration. ii. Intrauterine device. iii. Barrier method of contraception: condoms with or without a spermicidal agent, diaphragm or cervical cap with spermicide 10. Specific requirements of male participants (regarding contraception) will be defined in the ISAs based on the potential toxicity profile of the asset.
Exclusion Criteria:
3.1.1. Neuropathy Confound Exclusion Criteria 1. Peripheral neuropathy caused by a condition other than diabetes (e.g. HIV, cancer/chemotherapy-induced, other medication-induced, alcohol-induced, hereditary, autoimmune neuropathies, uncontrolled or untreated hypothyroidism). Note that participants will not be tested for HIV, this will be established by patient report or review of the medical record. 2. Other significant pain conditions involving the same area as the neuropathy (e.g. physical deformity of the feet, plantar fasciitis, lumbosacral radiculopathy with distal lower extremity pain, fibromyalgia involving the lower limbs, Morton's neuroma). 3. Other pain conditions not involving the same area as the neuropathy which (in the opinion of the investigator) interfere with the participant's ability to rate the neuropathy pain. 4. Any amputation of the lower limb which interferes with the participant's ability to rate the neuropathy pain. If there is any amputation please contact the MM. 5. The presence of any current foot ulcer. 6. Significant peripheral vascular disease defined as symptoms consistent with intermittent claudication. 3.1.2. Medication/Treatment Exclusion Criteria 7. Use of other investigational drugs within 3 months before screening and throughout the study. 8. Known or suspected hypersensitivity to all of the assets (active component and excipients) currently being tested in the Platform Protocol. 9. Undergone neurolytic or neurosurgical therapy or used an implanted neurostimulating device for neuropathic pain in the distal lower limbs within 3 months of screening. 10. Use of the high dose capsaicin patch (8%) in the 6 months before screening and throughout the study (for the treatment of PDPN). Use of the capsaicin patch in a manner that is not expected to interfere with the measurement of PDPN severity is allowed. 11. Participants who receive and are unwilling to discontinue episodic or periodic treatments for pain in the distal legs and/or feet (e.g., injections of local anesthetics) will be excluded. Non-pharmacological pain treatment (e.g. relaxation/hypnosis, physical or occupational therapy, any exercise-based therapy, any talk-based therapy, acupuncture, TENS) for the treatment of conditions other than PDPN is allowed. If the treatment is for PDPN it is allowed if it has been stable for at least 4 weeks prior to screening and is expected to remain stable throughout the study. 12. Active use of opioids or marijuana for any reason at screening and unwilling or unable to discontinue use. 3.1.3. Medical Exclusion Criteria 13. Clinically significant ECG or laboratory abnormalities at the Screening Visit that would put the participant at undue risk or affect the ability of the participant to participate in the trial (in the opinion of the investigator). Screening ECG and lab results may be repeated without requiring a rescreen, as long as the participant is still within the screening window. 14. Participants whose glycemic control has been unstable within 3 months before screening (e.g. ketoacidosis requiring hospitalization, any recent episode of hypoglycemia requiring assistance through medical intervention). 15. Proliferative retinopathy or maculopathy requiring acute treatment. 16. Requiring dialysis. 17. Myocardial infarction or stroke in the past 6 months. 18. Known diagnosis of moderate to severe hepatic impairment (equivalent to Child-Pugh class B or C) OR aspartate aminotransferase or alanine aminotransferase ≥ 3 times the upper limit of normal. 19. A clinically significant illness or operative procedure within 4 weeks of screening. 20. Clinically significant surgery planned during the study period. If a surgery is planned, please contact the MM. 21. History of or currently active malignancy or other medical condition that would put the participant at undue risk or affect the ability of the participant to participate in the trial (in the opinion of the investigator). 22. Pregnant or nursing (lactating) women. 3.1.4. Psychosocial and Substance Use Disorders Exclusion Criteria 23. A clinically significant psychiatric disease that would put the participant at undue risk or affect the ability of the participant to participate in the trial (in the opinion of the investigator). 24. Alcohol use disorder or other substance use disorders (other than nicotine or caffeine) in accordance with DSM-5 criteria within 12 months of screening. 25. Positive urine drug tests defined as follows: 1. Two positive urine drug tests for prescription opioids or marijuana, prior to the initiation of investigational product (IP); or 2. One positive urine drug test for any illegal drugs (other than marijuana) prior to the initiation of IP. 26. Vulnerable persons defined as either of the following: 1. Individuals whose willingness to volunteer in a clinical study may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation or of a retaliatory response from senior members of a hierarchy in case of refusal to participate. 2. Individuals whose judgment has been impaired by their physical, mental, or socio-economical condition and those incapable of giving informed consent.
Painful Diabetic Neuropathy, Other
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A Phase 1 in Patients With HLA-A*0201+ and WT1+ Recurrent/Metastatic Cancers

This is a Phase 1, open-label, 2-part, multi-center study evaluating the safety, tolerability, PK, pharmacodynamics (PD), immunogenicity, and antitumor activity of CUE-102 intravenous (IV) monotherapy in HLA-A*0201 positive patients with WT1 positive recurrent/metastatic solid tumors who have failed conventional therapies.
Nataliya Uboha, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT05360680
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Inclusion Criteria:
1. Ability to provide informed consent and documentation of informed consent prior to initiation of any study-related tests or procedures that are not part of standard of care for the patient's disease. 2. Age ≥18 years old 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 4. Life expectancy ≥12 weeks 5. Measurable disease as per RECIST 1.1 and documented by CT and/or MRI. 6. All tumors must have histologically or cytologically confirmed cancer diagnosis 7. Patients must have any of the following cancers to be eligible: A. Colorectal cancer 1. Histologically or cytologically documented adenocarcinoma of colon or rectum at the time of initial presentation 2. Metastatic or locally advanced/unresectable disease 3. Documented disease progression after the last administration of standard therapies or intolerance to at least 2 prior systemic treatment regimens (CUE-102 will be 3rd line therapy or greater). B. Gastric cancer (including gastroesophageal junction) 1. Histologically or cytologically documented gastric cancer at the time of initial presentation 2. Metastatic or locally advanced/unresectable disease 3. Documented disease progression after last administration of standard therapies or intolerance to standard therapies. (CUE-102 will be 2nd line therapy or greater). C. Pancreatic cancer 1. Histologically or cytologically documented pancreatic adenocarcinoma at the time of initial presentation 2. Patients with metastatic or locally advanced/unresectable disease. 3. Prior systemic treatment must include either a fluoropyrimidine-based or gemcitabine-based regimen in either the (neo)adjuvant or relapsed setting. (CUE-102 will be 2nd line therapy or greater). D. Ovarian cancer 1. Histologically or cytologically documented ovarian cancer at the time of initial presentation 2. Metastatic or locally advanced/unresectable disease, with documented disease progression after last administration of standard therapies or intolerance to standard therapies. 3. Prior systemic treatment must include a platinum-based regimen. (CUE-102 will be 2nd line therapy or greater). 4. For patients determined to have platinum-sensitive disease, treatment with a second platinum-based combination regimen +/- bevacizumab should be considered prior to treatment with CUE-102 (CUE-102 will be 3rd line therapy or greater). 8. Patient must have HLA-A*0201 genotype as determined by genomic testing. 9. Patient must have histologically and/or cytologically proven tumor(s) that is WT1 positive. 10. Acceptable laboratory parameters. 11. Female patients of childbearing potential must agree to use acceptable contraceptive measures from the time of main study consent through 90 days after discontinuation of study drug administration. 12. Non-vasectomized male patients with partners of childbearing potential must use barrier contraception from the time of main study consent through 90 days after discontinuation of study drug. 13. Patients who have previously received an immune CPI (e.g., anti-programmed cell death ligand 1 (anti PD-L1), anti-programmed cell death 1 (anti-PD-1), anti-cytotoxic T lymphocyte-associated antigen 4 [CTLA-4]) prior to enrollment must have toxicities related to the CPI resolved to CTCAE ≤ Grade 1 or baseline (level prior to the CPI) to be eligible for enrollment. Patients who have experienced CPI-related endocrinopathies (e.g., diabetes, adrenal insufficiency) may participate if endocrinopathies are controlled (CTCAE ≤ Grade 1) with endocrinology support and appropriate repletion. Note: Patients who experienced previous hypothyroidism toxicity on a CPI are eligible to enter study regardless of CTCAE grade resolution as long as the patient is well controlled on thyroid replacement hormone.
Exclusion Criteria:
1. Female patients who are pregnant or plan to become pregnant during the course of the trial 2. Female patients who are breastfeeding 3. Patients with symptomatic central nervous system (CNS) metastases must have been treated, be asymptomatic, and not have any of the following at the time of enrollment: 1. Need for concurrent treatment for the CNS disease (e.g., surgery, radiation, corticosteroids >10 mg prednisone/day or equivalent) 2. Progression of CNS metastases on CT or MRI for at least 28 days after last day of prior therapy for the CNS metastases 3. Concurrent leptomeningeal disease or cord compression. 4. Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is permitted. 5. History of prior allogeneic bone marrow, stem-cell, or solid organ transplantation 6. Treatment with any systemic anti-neoplastic therapy, or investigational therapy within the 14 days (or 28 days, for antibody drugs), before the first dose of CUE-102. 7. Treatment with radiation therapy within 14 days before the first dose of CUE-102 8. Treatment with corticosteroids (> 10 mg per day prednisone or equivalent) or other immune suppressive drugs within 14 days before the first dose of CUE-102. Steroids for topical, ophthalmic, inhaled, or nasal administration are permitted. Physiological replacement with up to a maximum dose of 5 mg equivalence of prednisone per day is permitted. 9. History of clinically significant cardiovascular disease 10. Clinically significant pulmonary compromise (e.g., requirement for supplemental oxygen) 11. Clinically significant gastrointestinal (GI) disorders 12. Patients who experienced the following immune CPI-related AEs are ineligible even if the AE resolved to ≤ Grade 1 or baseline: 1. ≥ Grade 3 ocular AE 2. Changes in liver function tests that met the criteria for Hy's Law (> 3× ULN of either ALT/AST with concurrent > 2× ULN of total bilirubin (total and direct) and without alternate etiology) 3. ≥ Grade 3 neurologic toxicity 4. ≥ Grade 3 colitis 5. ≥ Grade 3 renal toxicity 13. Evidence of active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 7 days before the first dose of CUE-102. 14. No known history of infection or positive test for HIV, Hepatitis B or Hepatitis C, testing prior to enrollment is not required unless mandated by local authority 15. Second primary invasive malignancy that has not been in remission for > 2 years. 16. History of trauma or major surgery within 28 days before the first dose of CUE-102 17. Any serious underlying medical or psychiatric condition that would impair the ability of the patient to receive or tolerate the planned treatment at the investigational site 18. Known hypersensitivity to recombinant proteins, polysorbate 80 or any excipient contained in the drug formulation for CUE-102 19. Vaccination with any live virus vaccine within 28 days before the first dose of CUE-102. Inactivated annual influenza vaccination is allowed. 20. Dementia or altered mental status that would preclude understanding and rendering of informed consent 21. Active or history of significant alcohol or other substance abuse within 1 year before the first dose of CUE-102
Colorectal Cancer, Gastric Cancer, Pancreatic Cancer, Ovarian Cancer, Esophagus, Stomach, Colon, Pancreas, Other Digestive Organ, Ovary, Colon and Rectum, Gastrointestinal cancers, other
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A Study of Tazemetostat With Rituximab and Abbreviated Bendamustine in the Frontline Treatment of High Tumor Burden Follicular Lymphoma

This study is planned as a single arm clinical trial of tazemetostat in combination with bendamustine and rituximab with both a phase I and phase II component. All patients will receive tazemetostat twice daily on days 1-28 in combination with bendamustine 90 mg/m2 IV on days 1 and 2 and rituximab 375 mg/m2 IV on day 1 of a 28-day cycle for up to three cycles. Following this, patients will receive tazemetostat twice daily on days 1-28 and rituximab 375 mg/m2 IV on day 1 of a 28-day cycle for up to three cycles.
Vaishalee Kenkre, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT05551936
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Inclusion Criteria:

• Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0-2 within 10 days prior to registration.
• Low grade follicular lymphoma (grade 1-2 or 3A by WHO-HAEM4R and/or cFL by WHO-HAEM5). Specifically, grade 3B or FLBL will not be allowed. Must not have evidence of transformed lymphoma at the time of study enrollment.
• Stage II, III, or IV by Ann Arbor staging system.
• Meet the definition of high tumor burden follicular lymphoma as defined by Groupe d'Etude des Lymphomes Follicularies (GELF) Criteria or be defined as high risk by the follicular lymphoma international prognostic index (FLIPI) 1 or FLIPI 2. --GELF Criteria (Must meet ≥ 1 of the following)
• Any nodal or extranodal mass ≥ 7 cm in diameter
• Involvement of ≥ 3 nodal sites ≥ 3 cm
• Systemic or B symptoms
• Presence of serous effusion
• Splenic enlargement
• Risk of compression syndrome (epidural, ureteral, etc)
• Leukemic phase of disease
• Cytopenia deemed due to disease involvement (hemoglobin < 10, granulocyte count < 1.5×10^9/L, or platelet count < 100×10^9/L)
• In addition to meeting GELF criteria, must have at least one FDG-avid site on PET that measures 1.5 cm in at least one dimension of a nodal site or 1cm in at least one dimension for extranodal sites.
• Received no prior therapy except local radiation therapy (field did not exceed 2 adjacent nodal regions), single agent rituximab (limited to 4 doses), or steroids for symptom control in the 28 days preceding trial enrollment.
• Must have prior EZH2 testing already performed or have tissue available to perform retrospective EZH2 testing. If prior EZH2 results are not available, tissue must be submitted. Tissue block is preferred but unstained slides are also acceptable. Patients who have insufficient or suboptimal tissue must be willing to have a biopsy performed prior to starting study drugs. See Correlative Lab Manual for details.
• Demonstrate adequate organ function as defined below; all screening labs to be obtained within 28 days prior to registration.
• Hematological
• Platelets ≥ 50 K/dL
• Absolute Neutrophil Count (ANC) ≥ 1000 K/mm3
• Hemoglobin (Hgb) ≥ 8 g/dL
• Renal
• Calculated creatinine clearance ≥ 40 mL/min using the Cockcroft-Gault formula
• or Serum creatinine < 2 mg/dL
• Hepatic
• Bilirubin ≤ 1.5 × upper limit of normal (ULN)
• Aspartate aminotransferase (AST) ≤ 3 × ULN
• Alanine aminotransferase (ALT) ≤ 3 × ULN
• Coagulation ---International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) ≤ 2 × ULN
• Females of childbearing potential with a male partner able to father a child must have a negative serum or urine pregnancy test within 7 days prior to registration. See the protocol for definition of childbearing potential.
• Females of childbearing potential must be willing to abstain from vaginal intercourse or use an effective method(s) of contraception from the time of informed consent, during the study and for 6 months after the last dose of study drug(s). Males able to father a child must be willing to abstain from vaginal intercourse or to use an effective method(s) of contraception from initiation of treatment, during the study and for 3 months after the last dose of study drug(s). See the protocol.
• As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.
Exclusion Criteria:

• Active infection requiring systemic therapy with 4 weeks of study drug administration.
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
• Concurrent malignancy or malignancy within the last 3 years (except for ductal breast cancer in situ, non-melanoma skin cancer, prostate cancer not requiring treatment, and cervical carcinoma in situ) whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are not eligible for this trial.
• Active central nervous system (CNS) metastases or leptomeningeal disease. NOTE: Subjects who are symptomatic and have not undergone prior brain imaging must undergo a head computed tomography (CT) scan or brain MRI within 28 days prior to registration to exclude brain metastases.
• Treatment with any investigational drug within 4 weeks prior to registration.
• Subjects who require chronic use of moderate or strong CYP3A4/5 inhibitors or inducers within 28 days prior to registration.
• Clinically significant acute infection requiring systemic antibacterial, antifungal, or antiviral therapy.
• Known Uncontrolled Human Immunodeficiency Virus infection. Testing not required. NOTE: If a subject is known to have HIV/AIDS, then they will be allowed on study with adequate antiviral therapy, no detectable viral load, and stable on antiviral treatment for ≥ 4 weeks prior to first dose of study drug(s).
• Known hepatitis C infection. Testing not required. NOTE: If hepatitis C antibody test is known positive, patients are excluded unless a hepatitis C virus ribonucleic acid (HCV RNA) is negative.
• Must be tested for hepatitis B within 28 days of registration: including hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B core antibody. A positive hepatitis B core antibody should be followed by hepatitis B DNA PCR testing to confirm or rule out active infection. Patients with hepatitis B surface antigen and/or detectable hepatitis B DNA PCR are not allowed on study. Patients with a positive hepatitis B core antibody but negative hepatitis B surface antigen and hepatitis B DNA PCR will be allowed on study, but hepatitis B prophylactic treatment should be strongly considered.
• Clinically significant cardiovascular disease or cardiac insufficiency (New York Heart Association classes III-IV), cardiomyopathy, preexisting clinically significant arrhythmia, acute myocardial infarction within 3 months of enrollment, angina pectoris within 3 months of enrollment.
Follicular Lymphoma, Non-Hodgkin's Lymphoma, Lymphoma
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Comparison of Anti-coagulation and Anti-Platelet Therapies for Intracranial Vascular Atherostenosis (CAPTIVA)

The primary goal of the trial is to determine if the experimental arms (rivaroxaban or ticagrelor or both) are superior to the clopidogrel arm for lowering the 1-year rate of ischemic stroke, intracerebral hemorrhage, or vascular death.
Azam Ahmed, MD
All
30 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05047172
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Inclusion Criteria:

• Acute focal symptoms or signs of any duration associated with imaging, pathological, or other objective evidence of arterial infarction OR clinical evidence of cerebral, spinal cord, or retinal focal arterial ischemic injury based on symptoms persisting greater than or equal to 24 hours that occurred within 30 days prior to randomization
• Index stroke is attributed to 70-99% stenosis (or flow gap on MRA) of a major intracranial artery (carotid artery, middle cerebral artery (M1 or M2), vertebral artery (V4), basilar artery, posterior cerebral artery (P1), or anterior cerebral artery (A1)) documented by CTA, MRA, or catheter angiography
• Modified Rankin Scale score of ≤ 4, at time of consent
• Ability to swallow pills
• At least 30 years of age, inclusive, at time of consent
• Subjects 30-49 years of age are required to meet at least ONE of the following additional criteria below to qualify for the study: 1. diabetes treated with insulin for at least 15 years 2. at least 2 of the following atherosclerotic risk factors: hypertension (BP > 140/90 or on antihypertensive therapy); dyslipidemia (LDL > 130 mg /dl or HDL < 40 mg/dl or fasting triglycerides > 150 mg/dl or on lipid lowering therapy); smoking; non-insulin dependent diabetes or insulin dependent diabetes of less than 15 years duration; any of the following vascular events occurring in a parent or sibling who was < 55 years of age for men or < 65 years of age for women at the time of the event: myocardial infarction, coronary artery bypass, coronary angioplasty or stenting, stroke, carotid endarterectomy or stenting, peripheral vascular surgery for atherosclerotic disease 3. personal history of any of the following: myocardial infarction, coronary artery bypass, coronary angioplasty or stenting, carotid endarterectomy or stenting, or peripheral vascular surgery for atherosclerotic disease 4. any stenosis of an extracranial carotid or vertebral artery, another intracranial artery, subclavian artery, coronary artery, iliac or femoral artery, other lower or upper extremity artery, mesenteric artery, or renal artery that was documented by non-invasive vascular imaging or catheter angiography and is considered atherosclerotic 5. aortic arch atheroma documented by non-invasive vascular imaging or catheter angiography 6. any aortic aneurysm documented by non-invasive vascular imaging or catheter angiography that is considered atherosclerotic
• Negative pregnancy test in a female who has had any menses in the last 18 months and has not had surgery that would make her unable to become pregnant
• Subject is willing and able to return for all follow-up evaluations required by the protocol
• Subject is available by phone
• Subject understands the purpose and requirements of the study and can make him/herself understood
• Subject has provided informed consent (use of a LAR is not permitted)
Exclusion Criteria:

• Previous treatment of target lesion with a stent, angioplasty, or other mechanical device, including mechanical thrombectomy for the qualifying stroke, or plan to perform one of these procedures
• Plan to perform concomitant endarterectomy, angioplasty or stenting of an extracranial vessel tandem to the symptomatic intracranial stenosis
• Intracranial tumor (except meningioma) or any intracranial vascular malformation
• Thrombolytic therapy within 24 hours prior to randomization
• Progressive neurological signs within 24 hours prior to randomization
• History of any intracranial hemorrhage (parenchymal, subarachnoid, subdural, epidural)
• Intracranial arterial stenosis due to: arterial dissection; MoyaMoya disease; any known vasculitic disease; herpes zoster, varicella zoster or other viral vasculopathy; neurosyphilis; any other intracranial infection; any intracranial stenosis associated with CSF pleocytosis; radiation induced vasculopathy; fibromuscular dysplasia; sickle cell disease; neurofibromatosis; benign angiopathy of central nervous system; postpartum angiopathy; suspected vasospastic process; reversible cerebral vasoconstriction syndrome (RCVS); suspected recanalized embolus
• Presence of any of the following unequivocal cardiac sources of embolism: chronic or paroxysmal atrial fibrillation, mitral stenosis, mechanical valve, endocarditis, intracardiac clot or vegetation, myocardial infarction within three months, left atrial spontaneous echo contrast
• Known allergy or contraindication to aspirin, rivaroxaban, clopidogrel, or ticagrelor
• Uncontrolled severe hypertension (systolic pressure > 180 mm Hg or diastolic pressure > 115 mm Hg), active peptic ulcer disease, major systemic hemorrhage within 30 days prior to randomization, active bleed or bleeding diathesis, platelets < 100,000, hematocrit < 30, INR > 1.5, clotting factor abnormality that increases the risk of bleeding, current alcohol or substance abuse, severe liver impairment (AST or ALT > 3 x normal, cirrhosis), or CrCl < 15 mL/min or on dialysis
• Major surgery (including stenting of any vessel; open femoral, aortic, or carotid surgery; or cardiac surgery) within previous 30 days prior to randomization or planned in the next 90 days after randomization
• Any condition other than intracranial arterial stenosis that requires the subject to take any antithrombotic medication other than aspirin (NOTE: exceptions allowed for subcutaneous heparin for deep vein thrombosis (DVT) prophylaxis)
• Dementia or psychiatric problem that prevents the subject from following an outpatient program reliably
• Co-morbid conditions that may limit survival to less than 12 months
• Pregnancy or of childbearing potential and unwilling to use contraception for the duration of this study, or currently breastfeeding
• Current or anticipated concomitant oral or intravenous therapy with strong CYP3A4 inhibitors or CYP3A4 substrates that cannot be stopped for the course of this study
• Enrollment in another study that would conflict with the current study
Other, Brain & Neurological, Intracranial Arteriosclerosis, Stroke
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This Study Aims to Find the Best Dose of BI 907828 (Brigimadlin) in Patients With Different Types of Advanced Cancer (Solid Tumors)

This study is open to adults with different types of advanced cancer (solid tumors). The purpose of this study is to find out the most suitable dose of BI 907828 (brigimadlin) the participants can tolerate. The most suitable dose is used in the second part to find out whether brigimadlin makes tumors shrink. In this study, brigimadlin is given to humans for the first time. Brigimadlin is a so-called MDM2 inhibitor that is being developed to treat cancer. Brigimadlin is taken as a tablet. Participants either take a dose of brigimadlin on one day every 3 weeks or on two days every 4 weeks. The participants are in the study for as long as they benefit from and can tolerate treatment. The doctors regularly check the participants' general health during the study.
Jeremy Kratz, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT03449381
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Inclusion Criteria:

• Provision of signed and dated, written informed consent form ICF in accordance with ICH-GCP and local legislation prior to any trial-specific procedures, sampling, or analyses.
• Pathologically documented, advanced solid tumors.
• Patients fulfilling one or more of the following criteria:
• Radiologically documented disease progression or relapse
• Patients who are not eligible to receive standard of care treatments, and for whom no proven treatments exist.
• Patients with MDM2 amplified sarcomas who require first line treatment (for Ph Ib/dose expansion
•Cohort 1 only).
• Patients with MDM2 amplified sarcomas may fulfil any one of the above three criteria to be considered eligible.
• Phase Ia (dose escalation) only:
• Patient has a tumor with either a known TP53 wild type status, or unknown TP53 status, and regardless of MDM2 amplification status, at the time of study entry.
• Phase Ib (expansion phase) only:
• Cohort 1: TP53 wt and MDM2-amplified sarcoma with advanced/metastatic disease at any line of therapy. If TP53 status is not available during screening, the patient may be included with unknown TP53 status if a tissue sample is submitted for central laboratory assessment. If TP53 status cannot be evaluated, the patient may be included if agreed between the Investigator and Sponsor.
• Cohort 2: TP53 wt and MDM2- amplified NSCLC, urothelial, gastric, biliary tract (including cholangiocarcinoma, intra- and extrahepatic biliary tree, gall blander and ampulla of vater) or pancreatic solidPDAC tumors who have had at least one previous line of therapy for advanced/metastatic disease. If TP53 status cannot be evaluated the patient may be included if agreed between the Investigator and Sponsor
• Phase Ia (dose escalation) only:
• Patient with either measurable or non-measurable disease.
• Non-evaluable disease allowed.
• Phase Ib (expansion phase) only:
• At least one target lesion that can be accurately measured per RECIST v.1.1.
• Phase Ia:
• Patient must be willing to undergo blood sampling for PK, pharmacodynamic, biomarker, and PGx analyses.
• Phase Ib:
• Patient must be willing to undergo tumor biopsy sampling for pharmacodynamic analyses and blood sampling for PK, pharmacodynamics, and biomarker analyses.
• Willingness to provide a fresh tumor tissue sample obtained after relapse/ progression during or after prior therapy. In case a fresh biopsy cannot be obtained (e.g. inaccessible lesions or patient safety concern), an archived specimen, collected before screening within 12 months of enrollment, may be submitted. If these requirements cannot be met, then the patient may be allowed to enter the study at Sponsor discretion, after agreement between the Investigator and Sponsor.
• Further inclusion criteria apply
Exclusion Criteria:

• Previous administration of BI 907828 (brigimadlin) or any other MDM2-p53 or MDMX (MDM4)-p53 antagonist.
• Known TP53 mutant tumor.
• Symptomatic metastases from non-brain tumors. Note: Patients with previously treated brain metastases may participate provided they are stable, without evidence of progression by imaging (using the identical imaging modality for each assessment, either MRI or computed tomography (CT) scan), for at least four weeks prior to the first dose of trial treatment, and any neurologic symptoms have returned to baseline; have no evidence of new or enlarging brain metastases. Patients on corticosteroids must have a stable dose for at least 5 days prior to baseline MRI.
• Patients with history of bleeding diathesis.
• Major surgery (major according to the Investigator's assessment) performed within 12 weeks prior to start of study treatment, or planned within 12 months after screening (e.g. hip replacement).
• Any other documented active or suspected malignancy or history of malignancy within 3 years prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix, or other local tumors considered cured by local treatment.
• Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial.
• Further exclusion criteria apply.
Neoplasms, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
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Strata PATH™ (Precision Indications for Approved Therapies) (Strata PATH)

StrataPATH™ is a non-randomized, open-label trial designed to explore efficacy and safety of multiple FDA-approved and commercially available cancer therapies in new, biomarker-guided patient populations.
Mark Burkard, MD, PhD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05097599
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To be eligible to participate in this study, an individual must meet each of the criterion below and the criteria indicated in the selected biomarker/drug cohort appendix: 1. Male or female ≥18 years of age. 2. Pathologically confirmed solid tumor 3. Participants must be able to follow study visit schedule and willing to provide up to 20 mL of peripheral blood samples at the indicated time points 4. CGP results need to be from a test conducted in a CLIA approved laboratory and archival formalin-fixed, paraffin-embedded (FFPE) tumor tissue is required for confirmatory testing of non-Strata test results unless otherwise indicated within the cohort-specific protocol criteria. 5. Biomarker positive for the defined cohort 6. For individuals with non-primary, treated or stable brain metastases: No evidence of progression (defined as no radiographic evidence of progression) for at least 4 weeks prior to consent. 7. Adequate bone marrow, organ function & laboratory parameters as determined by the treating physician unless otherwise indicated within the cohort-specific protocol criteria. 8. Adequate cardiac function: 1) Left ventricular ejection fraction (LVEF) ≥ 50% and 2) QTc interval ≤ 470 ms (females) or ≤ 450 ms (males) average preferred. An individual who meets any of the following criteria will be excluded from participation in this study: 1. Receiving another cancer treatment 2. Major surgery within 4 weeks prior to study entry 3. Has received a systemic cancer treatment within 3 weeks of first study dose 4. Individuals with a history of a second malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years or are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers that have been diagnosed and treated within the past 3 years are eligible: cervical/prostate carcinoma in situ, superficial bladder cancer, non-melanoma cancer of the skin. Patients with other cancers diagnosed within the past 3 years and felt to be at low risk of recurrence should be discussed with the study principal investigator to determine eligibility. 5. Participant has primary central nervous system tumor. 6. A woman of childbearing potential who has a positive urine pregnancy test (within 72 hours) prior to treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 7. Females who are pregnant or nursing or plan to become pregnant or anyone unwilling to use contraception for the duration of treatment. 8. Ongoing toxicity of CTCAE grade >2, other than peripheral neuropathy, related to anticancer therapy that was completed within 4 weeks of consent. 9. Ongoing peripheral neuropathy of CTCAE grade >3. 10. History of stroke including transient ischemic attack (TIA) or acute myocardial infarction within 6 months of consent. 11. Participant has a known history of human immunodeficiency virus (HIV), Hepatitis B or known active Hepatitis C virus infection. 12. Medical condition that would place the patient at risk as a result of blood donation, such as bleeding disorder. 13. Any other clinically significant medical condition that, in the opinion of the treating physician, makes participation undesirable, including but not limited to ongoing or active infection, significant uncontrolled hypertension, or severe psychiatric illness.
Cancer, Advanced Solid Tumor, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
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Safety and Efficacy of IMC-F106C as a Single Agent and in Combination With Checkpoint Inhibitors

IMC-F106C is an immune-mobilizing monoclonal T cell receptor against cancer (ImmTAC ®) designed for the treatment of cancers positive for the tumor-associated antigen PRAME. This is a first-in-human trial designed to evaluate the safety and efficacy of IMC-F106C in adult patients who have the appropriate HLA-A2 tissue marker and whose cancer is positive for PRAME
Vincent Ma, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04262466
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Inclusion Criteria:
1. ECOG PS 0 or 1 2. HLA-A*02:01 positive 3. PRAME positive tumor 4. Relapsed from, refractory to, or intolerant of standard therapy 5. If applicable, must agree to use highly effective contraception 6. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the Informed Consent (ICF) and protocol
Exclusion Criteria:
1. Symptomatic or untreated central nervous system metastasis 2. Recent bowel obstruction 3. Ascites requiring recurrent paracentesis 4. Significant immune-mediated adverse event with prior immunotherapy (patients in checkpoint inhibitor combination treatment) 5. Inadequate washout from prior anticancer therapy 6. Significant ongoing toxicity from prior anticancer treatment 7. Out-of-range laboratory values 8. Clinically significant lung, heart, or autoimmune disease 9. Ongoing requirement for immunosuppressive treatment 10. Prior solid organ or bone marrow transplant 11. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection 12. Known history of human immunodeficiency virus (HIV) 13. Significant secondary malignancy 14. Hypersensitivity to study drug or excipients 15. Antibiotics, vaccines or surgery within 2-4 weeks prior to the first dose of study intervention 16. Pregnant or lactating 17. Any other contraindication for applicable combination partner based on local prescribing information
Lung, Melanoma, Skin, Breast, Corpus Uteri, Ovary, Urinary Bladder, Other Urinary, Bladder, Genitourinary cancers, other, Melanoma/Skin cancer, Uterus, Select Advanced Solid Tumors
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A Prospective Registry Study to Assess Real-world Patient Characteristics, Treatment Patterns, and Longitudinal Outcomes in Patients Receiving Mavacamten and Other Treatments for Symptomatic Obstructive Hypertrophic Cardiomyopathy (Obstructive HCM) (DISCOVER-HCM)

The purpose of this study is to evaluate the safety of mavacamten in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) treated in the real-world setting. The registry study also provide a real-world understanding of the current obstructive HCM patient population, treatment patterns, and clinical relevant outcomes for patients with symptomatic obstructive HCM in the US.
Aurangzeb Baber
All
18 Years and over
IV
This study is NOT accepting healthy volunteers
NCT05489705
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Inclusion Criteria:
1. Willing and able to provide written informed consent form (ICF) and any required privacy authorization prior to the initiation of study procedures. i. Diagnosis of obstructive HCM consistent with 2020 American Heart Association/American College of Cardiology (AHA/ACC) guidelines. ii. Obstructive HCM is defined clinically by the presence of increased LV wall thickness ≥ 15 mm (or ≥ 13 mm with positive family history of HCM) in a nondilated ventricular chamber that is not solely explained by abnormal loading conditions (eg, another cardiac or systemic disease) and peak LVOT gradient of ≥ 30 mmHg at rest or with provocation. 2. Has documented LVEF of ≥ 55% recorded by echocardiography within the last 6 months. 3. Symptoms consistent with NYHA functional class II-IV. 4. ≥ 18 years of age at the time of informed consent. 5. Receiving BBs, non-dihydropyridine calcium. channel blockers (non-DHP CCBs), disopyramide, and/or mavacamten (once available) as part of routine clinical care; or currently receiving no treatment due to intolerance or failure of prior treatment (eg, BBs, non-DHP CCBs, or disopyramide) for obstructive HCM.
Exclusion Criteria:
1. Known phenocopy disease (eg, Fabry disease, amyloidosis) or LV hypertrophy associated with hypertension. 2. Documentation of any fixed obstruction of the outflow tract such as aortic valve stenosis or replacement. 3. Prior treatment of obstructive HCM with invasive septal reduction (surgical myectomy or percutaneous alcohol septal ablation [ASA]) within 6 months prior to enrollment; participants with an unsuccessful myectomy or percutaneous ASA performed > 6 months prior to enrollment may be enrolled. 4. Naïve to treatment for obstructive HCM (ie, never treated with BBs, non-DHP CCBs, or disopyramide). 5. Receiving an investigational therapeutic agent for obstructive HCM (eg, myosin-inhibitors other than mavacamten) in an interventional clinical trial at participant enrollment. 6. Previously or currently enrolled in a long-term safety extension study of mavacamten (eg, EXPLORER-HCM [ClinicalTrials.gov, NCT03470545], MAVA-LTE [NCT03723655], PIONEER-OLE [NCT03496168], VALORHCM [NCT04349072], or MAVERICK [NCT03442764])
Cardiomyopathy, Cardiomyopathy, unspecified, Diastolic (congestive) heart failure, Systolic (congestive) heart failure, Other, Obstructive Hypertrophic Cardiomyopathy
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Testing the Safety and Tolerability of the Anti-cancer Drugs Trastuzumab Deruxtecan and Neratinib for Cancers With Changes in the HER2 Gene

This phase I trial tests the safety, side effects, and best dose of neratinib in combination with trastuzumab deruxtecan in treating patients with solid tumors that have spread to other parts of the body (metastatic) or that cannot be removed by surgery (unresectable), and have changes in a gene called human epidermal growth factor receptor 2 (HER2). Neratinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals tumor cells to multiply. This helps slow or stop the spread of tumor cells. Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates. It is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive tumor cells in a targeted way and delivers deruxtecan to kill them. Adding neratinib to trastuzumab deruxtecan may be able to shrink cancer with a change in the HER2 gene.
Nataliya Uboha, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT05372614
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Inclusion Criteria:

• Patients must have histologically confirmed malignancy that is metastatic or unresectable with participation in this clinical trial determined to be the best option for next treatment in the opinion of the investigator
• Patients must have a solid tumor with HER2-positivity as determined by any one or more of the following:
• HER2 overexpression defined by IHC 3+
• ERBB2 amplification by ISH or next-generation sequencing as determined by any CLIA certified lab
• A known HER2 activating mutation
• HER2 overexpression by IHC/ISH will follow histology specific ASCO-CAP guidelines for breast and gastric cancers. For tumor histologies without specific guidelines the following criteria will apply:
• HER2 IHC should be performed first, followed by ISH methods in cases showing 2+ (equivocal) expression by IHC. Positive (IHC 3+) or negative (IHC 0 or 1+) do not require further ISH testing. Cases with HER2:CEP17 ratio ≥2 or an average HER2 copy number ≥6.0 signals per cell are considered positive by ISH
• Known HER2 activating mutations:
• G309A/E
• S310F/Y
• S653C
• V659E
• G660D
• R678Q
• E693K
• Q709L
• L755S/P
• Del. 755-759
• D769Y/H
• G776V/C
• V777L
• V842I
• T862A
• L869R
• H878Y
• All exon 20 insertions, including:
• A771_Y772insYVMA
• A775_G776insYVMA
• Y772_A775dup
• P780_Y781insGSP
• G778_P780dup
• V697L
• T733I
• D769N
• L841V
• L866M
• R896C
• If a different mutation is identified, contact the study chair for conferral. Synonymous mutations are not eligible
• Patients must have received at least 1 prior line of therapy in the advanced/metastatic setting. No limitation on number of prior therapies; however, patients may not have received neratinib or DS-8201a previously. Prior HER2-targeted therapy other than neratinib or DS-8201a is allowed (e.g., trastuzumab, pertuzumab, TDM-1, lapatinib, etc.)
• Age >= 18 years. Because no dosing or adverse event data are currently available on the use of neratinib in combination with DS-8201a in patients < 18 years of age, children are excluded from this study
• Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
• Hemoglobin >= 9.0 g/dL (>= 8.0 g/dL for gastric cancer [GC] only) (within 14 days of enrollment)
• No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment
• Serum albumin >= 2.5 g/dL (within 14 days of enrollment)
• Leukocytes >= 3.0 K/cumm (within 14 days of enrollment)
• Absolute neutrophil count >= 1.5 K/cumm (within 14 days of enrollment)
• No administration of granulocyte colony-stimulating factor (G-CSF) is allowed within 1 week prior to screening assessment
• Platelets >= 100 K/cumm (within 14 days of enrollment)
• No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment
• Total bilirubin =< 1.5 × institutional upper limit of normal (ULN), (< 3 × ULN in the presence of documented Gilbert's syndrome or liver metastases at baseline) (within 14 days of enrollment)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x ULN (if liver metastases are present =< 5 x ULN) (within 14 days of enrollment)
• International normalized ratio (INR)/prothrombin time (PT) and activated partial thromboplastin time (aPTT) =< 1.5 x institutional ULN (within 14 days of enrollment)
• This applies only to patients who are not receiving therapeutic anticoagulation that may affect INR. Those who are on therapeutic anticoagulation, should be on a stable dose for 4 weeks and should be considered within therapeutic range
• Creatinine =< 1.5 x institutional ULN OR Glomerular filtration rate (GFR) >= 30 mL/min/1.73 m^2 (using the Cockcroft-Gault equation) (within 14 days of enrollment)
• Patients who are human immunodeficiency virus (HIV)-positive may participate IF they meet the following eligibility requirements:
• They must be stable on their anti-retroviral regimen, and they must be healthy from an HIV perspective
• They must have a CD4 count of greater than 250 cells/mcL over the past 6 months on this same anti-retroviral regimen and must not have had a CD4 count < 200 cells/ul over the past 2 years, unless it was deemed related to THE CANCER AND/OR CHEMOTHERAPY-induced bone marrow suppression
• For patients who have received chemotherapy in the past 6 months, a CD4 count < 250 cells/ul during chemotherapy is permitted as long as viral loads were undetectable during this same chemotherapy
• They must have an undetectable viral load and a CD4 count >= 250 cells/uL within 7 days of enrollment
• They must not be currently receiving prophylactic therapy for an opportunistic infection and must not have had an opportunistic infection within the past 6 months HIV-infected patients should be monitored every 12 weeks for viral load and CD4 counts
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Patients with treated brain metastases are eligible if the following criteria are met: 1) follow-up brain imaging done at least in 4 weeks after central nervous system (CNS)-directed therapy shows no evidence of progression and 2) the patient no longer requires steroids, or is on a stable steroid dose > 4 weeks
• Patients with radiographically new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible only if has no progressive clinical symptoms and if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy
• Patients should be New York Heart Association functional classification of class 2B or better
• Patients must have left ventricular ejection fraction (LVEF) >= 50% by either an echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before randomization/enrollment
• Dose expansion phase (PD cohort): Patients must have disease that is evaluable or measurable by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Dose expansion phase (PD cohort): Patients must have at least one lesion suitable for biopsy without significant risk to the patient. The biopsiable lesion can be the same as the evaluable lesion for response by RECIST 1.1
• Patients who had clinically significant side effects from prior cancer therapy must have recovered to grade 1 or below
• HER2 antibody conjugated to a topoisomerase 1 inhibitor agents as well as other therapeutic agents used in this trial are known to be teratogenic; thus, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for at least 1 month after the last dose of neratinib, or at least 7 months after the last dose of DS-8201a, whichever is longer (women of childbearing potential [WOCBP] only). Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after the last dose of neratinib, or 4 months after completion of DS-8021a administration, whichever is longer
• Women of non-child-bearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases, a blood sample with simultaneous follicle-stimulating hormone [FSH] > 40 mIU/mL and estradiol < 40 pg/mL [< 147 pmol/L] is confirmatory) are eligible. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods outlined for women of child-bearing potential if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method
• Male subjects must not freeze or donate sperm starting at screening and throughout the study period, and at least 4 months after the final study drug administration. Preservation of sperm should be considered prior to enrollment in this study
• Female subjects must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 7 months after the final study drug administration
• Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity who have a legally-authorized representative (LAR) and/or family member available will also be eligible
Exclusion Criteria:

• With the exception of medications that are under investigation in the study (e.g., standard of care, comparators, or combination therapies), the following medications, treatment, and procedures will be prohibited during the treatment period. The sponsor must be notified if a subject receives any of these during the study:
• Other anticancer therapy, including small-molecule targeted agents within 2 weeks or five half-lives, whichever is longer; chemotherapy otherwise not specified (including, but not limited to cytotoxic chemotherapy, antibody drug conjugates, retinoid therapy, hormonal therapy) within 3 weeks; immunotherapy or monoclonal antibody within 4 weeks; and nitrosureas or mitomycin C within 6 weeks (concurrent use of hormones for noncancer-related conditions [e.g., insulin for diabetes and hormone replacement therapy] is acceptable)
• Other investigational therapeutic agents
• Patients who have had major surgery or radiation within 4 weeks; palliative stereotactic radiation within 2 weeks (except for palliative radiation to known metastatic sites as long as it does not affect assessment of response or interrupt treatment for more than the maximum time specified in dose modification section)
• Radiotherapy to the thorax (palliative radiation to known metastatic sites in the thoracic spine is permitted in this study)
• Concomitant use of chronic systemic (IV or oral) corticosteroids or other immunosuppressive medications except for managing adverse events (inhaled steroids or intra-articular steroid injections are permitted in this study); chronic replacement dose steroids (e.g., for those with adrenal insufficiency) are permitted in this study
• Subjects with bronchopulmonary disorders who require intermittent use of bronchodilators (such as albuterol) will not be excluded from this study
• Concomitant treatment with chloroquine or hydroxychloroquine is not allowed during the study treatment due to concern for overlapping toxicities. If treatment with chloroquine and hydroxychloroquine treatment is absolutely required, study treatment must be interrupted. If chloroquine or hydroxychloroquine is administered, then a wash-out period of more than 14 days is required before restarting study treatment
• Patients with a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
• Patients with clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e. pulmonary emboli within three months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease (COPD), restrictive lung disease, pleural effusion, etc.), and any autoimmune, connective tissue or inflammatory disorders with potential pulmonary involvement (i.e. rheumatoid arthritis, Sjogren's, sarcoidosis, etc.), or prior pneumonectomy
• Patients with history of allergic reactions attributed to compounds of similar chemical or biologic composition to DS-8201a, the inactive ingredients in the drug product, or neratinib
• Patients who have a history of severe hypersensitivity reactions to other monoclonal antibodies
• Patients receiving any medications or substances that are moderate or strong inhibitors or inducers of CYP3A4 and P-glycoprotein are ineligible. Avoid concomitant use with proton pump inhibitors and P-glycoprotein substrates. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
• Patients with a medical history of myocardial infarction within 6 months before enrollment, or symptomatic congestive heart failure (CHF) (New York Heart Association class II to IV)
• Patients with a corrected QT interval (QTc) prolongation to > 470 ms (females) or > 450 ms (males) based on average of the screening triplicate 12-lead electrocardiogram (ECG)
• Patients with clinically significant corneal disease in the opinion of the investigator
• Patients with a pleural effusion, ascites, or pericardial effusion that requires drainage, peritoneal shunt, or cell-free and concentrated ascites reinfusion therapy (CART). (Drainage and CART are not allowed within 2 weeks prior to screening assessment) (GC indication)
• Patients with spinal cord compression
• Patients with an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
• Patients with unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to grade =< 1 or baseline. Subjects with chronic grade 2 toxicities may be eligible per the discretion of the investigator after consultation with the sponsor medical monitor or designee (e.g., grade 2 chemotherapy-induced neuropathy)
• Patients with substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, interfere with the subject's participation in the clinical study or evaluation of the clinical study results
• Pregnant women are excluded from this study because DS-8201a is a HER2 antibody conjugated to a topoisomerase 1 inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with DS-8201a, breastfeeding should be discontinued if the mother is treated with DS-8201a. These potential risks may also apply to other agents used in this study
• Prior treatment with neratinib or DS-8201a
• Clinically significant chronic gastrointestinal disorder with diarrhea as a major symptom; G2 or greater diarrhea at baseline. Please contact the study PI for any patient with more than two episodes of diarrhea per day averaged over at least a 7 day period at time of screening to determine whether the diarrhea would be considered clinically significant
• Inability to swallow tablets
• Patients with active additional malignancy or a personal history of additional malignancy that may affect outcome of disease under treatment (patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen at the discretion of the treating investigator are allowed)
• Patients with prior allogeneic organ transplantation including allogeneic stem cell transplantation
Malignant Solid Neoplasm, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
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OrganOx Metra® New Enrollment PAS

The objective of the OrganOx metra® New Enrollment Post-Approval Study is to collect data on the post-transplant clinical outcomes of DBD and DCD donor livers preserved and assessed on the OrganOx according to the current indications for use in the real-world setting.
David Al-Adra, MD
All
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT05526326
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Inclusion Criteria:

• Subject is 18 years of age or greater
• Subject is registered as an active recipient on the UNOS waiting list for liver transplantation
• Subject, or legally authorized representative, is able and willing to give informed consent and HIPAA authorization
• Subject is able and willing to comply with all study requirements (in the opinion of the Investigator)
Exclusion Criteria:

• Subject requiring all of the following at the time of transplantation: 1. Oxygen therapy via a ventilator/respirator 2. Inotropic support 3. Renal replacement therapy
• Subject has acute/fulminant liver failure (UNOS status 1A)
• Subject planned to undergo simultaneous transplantation of more than one organ (e.g., liver and kidney) from the same liver donor
• Subject is pregnant (as confirmed by urine or serum pregnancy test) or nursing
• Concurrent enrollment in another clinical study. Subjects enrolled in clinical studies or registries where only measurements and/or samples are taken (no test device or test drug) are allowed to participate.
Liver transplant, Other, Transplant, Digestive Health & Liver Disease, Liver Transplantation
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Treating Prostate Cancer That Has Come Back After Surgery With Apalutamide and Targeted Radiation Based on PET Imaging

This phase III trial tests two questions by two separate comparisons of therapies. The first question is whether enhanced therapy (apalutamide in combination with abiraterone + prednisone) added to standard of care (prostate radiation therapy and short term androgen deprivation) is more effective compared to standard of care alone in patients with prostate cancer who experience biochemical recurrence (a rise in the blood level of prostate specific antigen [PSA] after surgical removal of the prostate cancer). A second question tests treatment in patients with biochemical recurrence who show prostate cancer spreading outside the pelvis (metastasis) by positron emission tomography (PET) imaging. In these patients, the benefit of adding metastasis-directed radiation to enhanced therapy (apalutamide in combination with abiraterone + prednisone) is tested. Diagnostic procedures, such as PET, may help doctors look for cancer that has spread to the pelvis. Androgens are hormones that may cause the growth of prostate cancer cells. Apalutamide may help fight prostate cancer by blocking the use of androgens by the tumor cells. Metastasis-directed targeted radiation therapy uses high energy rays to kill tumor cells and shrink tumors that have spread. This trial may help doctors determine if using PET results to deliver more tailored treatment (i.e., adding apalutamide, with or without targeted radiation therapy, to standard of care treatment) works better than standard of care treatment alone in patients with biochemical recurrence of prostate cancer.
John Floberg, Assistant Professor
Male
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04423211
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Inclusion Criteria:

• STEP 0: REGISTRATION ELIGIBILITY CRITERIA
• Patient must be male and >= 18 years of age.
• Patient must have had a radical prostatectomy (RP) as definitive therapy for histopathologically-proven prostatic adenocarcinoma
• Patient must have biochemical recurrence (BCR) after RP, defined as follows:
• If time to BCR, defined as time to first detectable PSA ( > lower limit of normal for assay used) after RP, is < 12 months, a minimum PSA level of >= 0.2 ng/mL and a confirmatory reading of >= 0.2 ng/mL is required, per the American Urological Association (AUA) definition (Note: patients with a persistent PSA reading of at least 0.2 ng/mL are eligible)
• If time to BCR, defined as time to first detectable PSA (> lower limit of normal for assay used) after RP, is >= 12 months, a minimum absolute PSA of 0.5 ng/mL is required
• If the patient has a detectable PSA (> lower limit of normal for assay used) at any time after RP AND has an eligible baseline SOC PET (PET1) with at least one positive lesion in any location, then there is no minimum PSA requirement
• Patients must have no definite evidence for extrapelvic metastatic disease by conventional imaging modalities (CIM) (CT abdomen/pelvis or MRI abdomen/pelvis AND bone scintigraphy, or equivalent), within 26 weeks prior to Step 0 registration. If a patient only has a study-eligible PET/CT or PET/MR (i.e., PET done without prior CIM): if the PET is negative for extrapelvic lesions, then baseline CIM is NOT required. If the PET positive for extrapelvic lesions, then patient should have a baseline CT/MRI for soft tissue lesions and/or a bone scan for osseous lesions
• Study eligible = PET using FDA-approved radiotracer and performed within 16 weeks prior to study registration
• Extra-pelvic metastases is defined as any osseous metastases and/or any extrapelvic soft tissue, lymph nodes and organ metastases; extra-pelvic is defined as superior to common iliac bifurcation, outside of standard prostate bed + whole pelvis nodal RT fields. Baseline PET/CT or PET/MR scan (PET1) is eligible for this study if the SOC PET scan is completed with an FDA approved radiotracer for prostate cancer after Step 0 registration and prior to Step 1 randomization OR up to 16 weeks prior to Step 0 registration
• Patient must be a candidate for SOC post-prostatectomy radiation therapy (RT) to the prostate bed and pelvic nodes with androgen deprivation therapy (ADT)
• Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Patient must not have started ADT for biochemical recurrence prior to baseline PET (PET1) imaging. A short course of low-dose anti-androgen such as bicalutamide, given after baseline study PET/CT but prior to study registration, is permitted as a brief temporizing measure in advance of starting protocol-approved SOC ADT.
• Patient must not be enrolled in another therapeutic clinical trial
• Patient must be able to lie flat and still for approximately 20-30 minutes or otherwise tolerate a PET scan and radiation treatment planning and delivery
• Patients undergoing a PET/MR must meet local institutional safety guidelines for MRI
• Patient must not have history of seizures or known condition that may cause predisposal to seizures (e.g., stroke or head trauma resulting in loss of consciousness) within 1 year prior to registration
• Patient must not have history of inflammatory bowel disease or any gastrointestinal disorder affecting absorption that is expected to increase risk of complication from radiotherapy
• Hemoglobin (Hgb) >= 9.0 g/dL (independent of transfusion and/or growth factors within 3 months prior to Step 0 registration) (obtained within 8 weeks prior to Step 0 registration)
• Leukocytes >= 3,000/mcL (obtained within 8 weeks prior to Step 0 registration)
• Absolute neutrophil count >= 1,500/mcL (obtained within 8 weeks prior to Step 0 registration)
• Platelets >= 100,000/mcL (obtained within 8 weeks prior to Step 0 registration)
• Total bilirubin < 1.5 x institutional upper limit of normal (ULN) (patients with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, must have a direct bilirubin of < 1.5 x ULN to be eligible) (obtained within 8 weeks prior to Step 0 registration)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (obtained within 8 weeks prior to Step 0 registration)
• Creatine < 1.5 x instituional ULN (or measured creatinine clearance > 30 mL/min)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class I or II (by patient symptoms) or A or B (by objective assessment)
• Patient must not have completed a course of prior pelvic radiation therapy for any reason
• Patient must agree not to father children while on study
• Patient must be English or Spanish speaking to be eligible for the QOL component of the study
• NOTE: Sites cannot translate the associated QOL forms
• STEP 1: RANDOMIZATION ELIGIBILITY CRITERIA
• Patient must have completed a baseline SOC PET/CT or PET/MR (PET1 scan) using FDA approved radiotracer with results of extra-pelvic metastases involvement known (positive or negative). The PET1 must have been completed after Step 0 registration and prior to Step 1 randomization OR up to 12 weeks prior to Step 0 registration
• For patients with negative extra-pelvic metastases, PET-imaging status of intra-pelvic nodes must be known (positive or negative)
• For patients with positive extra-pelvic metastases (defined as any PET positive lesions outside of standard salvage RT fields [prostate bed +/- typical whole pelvis]), the number of extra-pelvic lesions must be known (1
•5 or > 5 extra-pelvic lesions)
Biochemically Recurrent Prostate Carcinoma, Metastatic Prostate Carcinoma, Prostate Adenocarcinoma, Stage IVB Prostate Cancer AJCC v8, Prostate
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A Study Evaluating the Long-term Safety and Efficacy of VX-121 Combination Therapy

The purpose of this study is to evaluate the long-term safety, tolerability, and efficacy of VX-121/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA) in participants with cystic fibrosis.
Andrew Braun
All
12 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05444257
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Key
Inclusion Criteria:

• Completed study drug treatment in a parent study VX20-121-102 (NCT05033080) and VX20-121-103 (NCT05076149); or had study drug interruption(s) in a parent study but did not permanently discontinue study drug, and completed study visits up to the last scheduled visit of the Treatment Period in the parent study Key
Exclusion Criteria:

• History of drug intolerance in a parent study
• Pregnant or breast-feeding females Other protocol defined Inclusion/Exclusion criteria may apply.
Cystic Fibrosis, Other, Lung & Respiratory
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BIVV020 (SAR445088) n Prevention and Treatment of Antibody-mediated Rejection (AMR)

Primary Objectives: - Cohort A: To evaluate the efficacy of BIVV020 in prevention of AMR - Cohort B: To evaluate the efficacy of BIVV020 in treatment of active AMR Secondary Objectives: - To assess the overall efficacy of BIVV020 in prevention or treatment of AMR - To characterize the safety and tolerability of BIVV020 in kidney transplant participants - To characterize the pharmacokinetic (PK) profile of BIVV020 in kidney transplant participants - To evaluate the immunogenicity of BIVV020
Fahad Aziz
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05156710
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Inclusion Criteria:
-Participant intended to receive SOC therapy per Investigator's judgment and local practice. Cohort A: Participants with chronic kidney disease who will receive a kidney transplant from a living or deceased donor. Cohort B: Participants who are kidney transplant recipients diagnosed with active AMR.
• BMI ≤ 40 kg/m2.
• Contraceptive use by women during the treatment period, and for at least 49 weeks after the last administration of IMP (BIVV020 + SOC arm participant) or last treatment period visit (SOC arm participant).
• Contraceptive use by men during the treatment period, and for at least 49 weeks after the last administration of IMP (BIVV020 + SOC arm participant) or last treatment period visit (SOC arm participant).
Exclusion Criteria:

• Participants who are ABO incompatible with their donors.
• Participants with known active ongoing infection as per below: 1. Positive HIV. 2. Positive HBV. 3. HCV with detectable HCV RNA. 4. Within 4 weeks of first study intervention: any serious infection, or any active bacterial infection, or any other infection which is clinically significant in the option of the Investigator, unless it can be confirmed that infection was cleared at least 3 days prior to first study intervention.
• History of active tuberculosis (TB) regardless of treatment.
• Participants with clinical diagnosis of systemic lupus erythematosus (SLE).
• Prior treatment with complement system inhibitor within 5 times the half-life.
• Current enrollment in any other clinical study where the last investigational study treatment administration was within 5 half-lives from study intervention initiation. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Transplant Rejection, Kidney transplant rejection, Other, Kidney Disease & Urinary, Transplant
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Collecting Blood Samples From Patients With and Without Cancer to Evaluate Tests for Early Cancer Detection

This study collects blood and tissue samples from patients with cancer and without cancer to evaluate tests for early cancer detection. Collecting and storing samples of blood and tissue from patients with and without cancer to study in the laboratory may help researchers develop tests for the early detection of cancers.
David Kosoff, MD
All
40 Years to 75 Years old
N/A
This study is also accepting healthy volunteers
NCT05334069
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Inclusion Criteria:

• Participants with a cancer diagnosis: Documentation of disease:
• Histologic documentation: Histologically confirmed diagnosis of invasive cancer
• Stage: Stage I-IV per American Joint Committee on Cancer (AJCC) 7th edition, with the exception of patients with leukemia, lymphoma, and multiple myeloma
• For leukemia: Type (chronic lymphocytic leukemia [CLL], chronic myeloid leukemia [CML], acute lymphoblastic lymphoma [ALL], acute myeloid leukemia [AML])
• For lymphoma: Stage I-IV based on Ann Arbor staging
• For multiple myeloma: Stage I, II, III based on Revised International Staging System (RISS)
• One of the following tumor types:
• Colorectal
• Bladder
• Head and neck
• Hepatobiliary
• Lung
• Lymphoma
• Leukemia
• Ovary *** For these specific cancer types only, patients may be enrolled prior to histologic confirmation of malignancy. Sites are required to contact the study chairs to review appropriateness for enrollment
• Pancreas *** For these specific cancer types only, patients may be enrolled prior to histologic confirmation of malignancy. Sites are required to contact the study chairs to review appropriateness for enrollment
• Multiple myeloma
• Gastric, esophageal or gastroesophageal
• Breast
• Thyroid
• Kidney
• For these specific cancer types only, patients may be enrolled prior to histologic confirmation of malignancy. Sites are required to contact the study chairs to review appropriateness for enrollment
• Endometrium
• Prostate
• Melanoma *** For these specific cancer types only, patients may be enrolled prior to histologic confirmation of malignancy. Sites are required to contact the study chairs to review appropriateness for enrollment
• Sarcoma
• Participants with a cancer diagnosis: No prior definitive systemic or local anti-cancer intervention
• Participants with a cancer diagnosis: Age >= 40 and =< 75
• Participants with a cancer diagnosis: No known current pregnancy by self-report
• Participants with a cancer diagnosis: No known or prior history of in situ or invasive malignancy (excluding in situ non-melanoma skin cancers) other than the current cancer diagnosis
• Participants with a cancer diagnosis: Willingness to provide blood samples for research use
• Participants with a cancer diagnosis: Absence of medical contraindications to a research blood draw volume of 60 mL
• Participants with a cancer diagnosis: No history of organ transplantation
• Participants with a cancer diagnosis: Ability to read and comprehend English or Spanish * Eligibility is restricted to individuals who can comprehend and read English or Spanish given that participation in the study will require the ability to read and complete questionnaires that are available only in those two languages
• Participants without a cancer diagnosis and without suspicion of cancer: Age >= 40 and =< 75
• Participants without a cancer diagnosis and without suspicion of cancer: No known current pregnancy by self-report
• Participants without a cancer diagnosis and without suspicion of cancer: No known or prior history of in situ or invasive malignancy (excluding in situ non-melanoma skin cancers)
• Participants without a cancer diagnosis and without suspicion of cancer: Willingness to provide blood samples for research use
• Participants without a cancer diagnosis and without suspicion of cancer: Absence of medical contraindications to a research blood draw volume of 60 mL
• Participants without a cancer diagnosis and without suspicion of cancer: No history of organ transplantation
• Participants without a cancer diagnosis and without suspicion of cancer: Ability to read and comprehend English or Spanish * Eligibility is restricted to individuals who can comprehend and read English or Spanish given that participation in the study will require the ability to read and complete questionnaires that are available only in those two languages
• Participants with a high suspicion of cancer: High suspicion of ovarian cancer, pancreatic cancer, kidney cancer, or melanoma by clinical and/or radiological assessment, with plans for histologic or cytologic confirmation within 28 days after study blood draw * Examples of highly suspicious cases include: elevated CA125 and abnormal transvaginal ultrasound, suspicious renal or pancreatic mass on imaging, suspicious cutaneous lesion concerning for melanoma
• Participants with a high suspicion of cancer: Central review of radiology reports and/or clinical documentation conducted by study chairs
• Participants with a high suspicion of cancer: Age >= 40 and =< 75
• Participants with a high suspicion of cancer: No known current pregnancy by self-report
• Participants with a high suspicion of cancer: No known or prior history of in situ or invasive malignancy (excluding in situ non-melanoma skin cancers) other than the current cancer diagnosis
• Participants with a high suspicion of cancer: Willingness to provide blood samples for research use
• Participants with a high suspicion of cancer: Absence of medical contraindications to a research blood draw volume of 60 mL
• Participants with a high suspicion of cancer: No history or organ transplantation
• Participants with a high suspicion of cancer: Ability to read and comprehend English or Spanish * Eligibility is restricted to individuals who can comprehend and read English and Spanish given that participation in the study will require the ability to read and complete questionnaires that are available only in those two languages
Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Mycosis Fungoides, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Multiple Myeloma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Leukemia, Lymphoma, Melanoma/Skin cancer, Uterus, Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Ann Arbor Stage I Lymphoma, Ann Arbor Stage II Lymphoma, Ann Arbor Stage III Lymphoma, Ann Arbor Stage IV Lymphoma, Chronic Lymphocytic Leukemia, Chronic Myeloid Leukemia, Gastroesophageal Junction Adenocarcinoma, Head and Neck Carcinoma, Hematopoietic and Lymphoid Cell Neoplasm, Invasive Breast Carcinoma, Kidney Carcinoma, Malignant Hepatobiliary Neoplasm, Malignant Solid Neoplasm, Melanoma, Muscle-Invasive Bladder Carcinoma, RISS Stage I Plasma Cell Myeloma, RISS Stage II Plasma Cell Myeloma, RISS Stage III Plasma Cell Myeloma, Sarcoma, Stage I Bladder Cancer AJCC v6 and v7, Stage I Breast Cancer AJCC v7, Stage I Colorectal Cancer AJCC v6 and v7, Stage I Esophageal Cancer AJCC V7, Stage I Gastric Cancer AJCC V7, Stage I Lung Cancer AJCC v7, Stage I Ovarian Cancer AJCC v6 and v7, Stage I Pancreatic Cancer AJCC v6 and v7, Stage I Prostate Cancer AJCC v7, Stage I Uterine Corpus Cancer AJCC v7, Stage II Bladder Cancer AJCC v6 and v7, Stage II Breast Cancer AJCC v6 and v7, Stage II Colorectal Cancer AJCC v7, Stage II Esophageal Cancer AJCC v7, Stage II Gastric Cancer AJCC v7, Stage II Lung Cancer AJCC v7, Stage II Ovarian Cancer AJCC v6 and v7, Stage II Pancreatic Cancer AJCC v6 and v7, Stage II Prostate Cancer AJCC v7, Stage II Uterine Corpus Cancer AJCC v7, Stage III Bladder Cancer AJCC v6 and v7, Stage III Breast Cancer AJCC v7, Stage III Colorectal Cancer AJCC v7, Stage III Esophageal Cancer AJCC v7, Stage III Gastric Cancer AJCC v7, Stage III Lung Cancer AJCC v7, Stage III Ovarian Cancer AJCC v6 and v7, Stage III Pancreatic Cancer AJCC v6 and v7, Stage III Prostate Cancer AJCC v7, Stage III Uterine Corpus Cancer AJCC v7, Stage IV Bladder Cancer AJCC v7, Stage IV Breast Cancer AJCC v6 and v7, Stage IV Colorectal Cancer AJCC v7, Stage IV Esophageal Cancer AJCC v7, Stage IV Gastric Cancer AJCC v7, Stage IV Lung Cancer AJCC v7, Stage IV Ovarian Cancer AJCC v6 and v7, Stage IV Pancreatic Cancer AJCC v6 and v7, Stage IV Prostate Cancer AJCC v7, Stage IV Uterine Corpus Cancer AJCC v7, Thyroid Gland Carcinoma
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SPEARHEAD-3 Pediatric Study

This is a pediatric basket study to investigate the safety and efficacy of afamitresgene autoleucel in HLA-A*02 eligible and MAGE-A4 positive subjects aged 2-21 years of age with advanced cancers
Christian Capitini, MD
All
2 Years to 21 Years old
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT05642455
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Inclusion Criteria:

• Age 2-21 years
• Body weight ≥ 10 kg
• Subject has histologically confirmed diagnosis of any one of the following cancers: (A) Synovial Sarcoma, (B) MPNST, (C) Neuroblastoma, or (D) Osteosarcoma
• Must have previously received a systemic chemotherapy
• Measurable disease according to RECIST v1.1 (or INCR, 2017 Neuroblastoma only).
• HLA-A*02 positive
• Tumor shows MAGE-A4 expression confirmed by central laboratory.
• Performance Status: ECOG 0-1 or Lansky Score ≥ 80
Exclusion Criteria:

• HLA-A*02:05 in either allele; or any A*02 having same protein sequence as HLA-A*02:05
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide.
• History of autoimmune or immune mediated disease
• Known central nervous system (CNS) metastases.
• Other prior malignancy that is not considered by the Investigator to be in complete remission
• Clinically significant cardiovascular disease
• Active infection with human immunodeficiency virus, hepatitis B virus, hepatitis C virus, or human T cell leukemia virus
• Pregnant or breastfeeding
Synovial Sarcoma, Malignant Peripheral Nerve Sheath Tumor (MPNST), Neuroblastoma, Osteosarcoma, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
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Colon Adjuvant Chemotherapy Based on Evaluation of Residual Disease (CIRCULATE-US)

This Phase II/III trial will evaluate the what kind of chemotherapy to recommend to patients based on the presence or absences of circulating tumor DNA (ctDNA) after surgery for colon cancer.
Dustin Deming, MD
All
18 Years and over
Phase 2/Phase 3
This study is NOT accepting healthy volunteers
NCT05174169
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Inclusion Criteria:
The patient must have an ECOG performance status of 0 or 1. Patients must have histologically/pathologically confirmed colon adenocarcinoma (T1-3, N1/N1c) with R0 resection accordingly to AJCC 8th edition criteria. NOTE: Patients with pathologic stages II or IIIC colon adenocarcinoma with R0 resection who have a commercially obtained Signatera™ ctDNA+ve assay result post-operatively meeting all timelines and eligibility requirements otherwise, are eligible for enrollment and inclusion in Cohort B. No radiographic evidence of overt metastatic disease within 28 days prior to study entry (CT with IV contrast or MRI imaging is acceptable and must include chest, abdomen, and pelvis). The distal extent of the tumor must be greater than or equal to 12 cm from the anal verge on colonoscopy or above the peritoneal reflection as documented during surgery or on pathology specimen (i.e., excluding rectal adenocarcinomas warranting treatment with chemoradiation). The patient must have had an en bloc complete gross resection of tumor (curative resection). Patients who have had a two-stage surgical procedure, to first provide a decompressive colostomy and then in a later procedure to have the definitive surgical resection, are eligible. The resected tumor specimen and a blood specimen from patients with Stage IIIA or Stage IIIB colon cancer must have central testing for ctDNA using the Signatera™ assay by Natera. NOTE: Patients with stage IIIA or IIIB colon cancer who otherwise meet eligibility criteria and have had ctDNA status checked with the Signatera™ assay as routine care outside of the study, are allowed to be enrolled, and will be retested and placed in either Cohort A or Cohort B depending on the central ctDNA testing result. NOTE: Patients with stage II or IIIC colon cancer who otherwise meet eligibility criteria and have had ctDNA status checked with the Signatera™ assay as routine care outside of the study AND have a ctDNA+ve result, are allowed to be enrolled. Patients will have central ctDNA testing, confirmed to be ctDNA+ve, and placed in Cohort B. Tumor must be documented as microsatellite stable or have intact mismatch repair proteins through CLIA-approved laboratory testing. Patients whose tumors are MSI-H or dMMR are excluded. The treating investigator must deem the patient a candidate for all potential agents used in this trial (5FU, LV, oxaliplatin and irinotecan). The interval between surgery (post-operative Day 7) and study entry must be no more than 60 days. Availability and provision of adequate surgical tumor tissue for molecular diagnostics and confirmatory profiling. Adequate hematologic function within 28 days before study entry defined as follows:
• Absolute neutrophil count (ANC) must be greater than or equal to 1500/mm3;
• Platelet count must be greater than or equal to 100,000/mm3; and
• Hemoglobin must be greater than or equal to 9 g/dL. Adequate hepatic function within 28 days before study entry defined as follows:
• total bilirubin must be less than or equal to ULN (upper limit of normal) for the lab and
• alkaline phosphatase must be less than 2.5 x ULN for the lab; and
• AST and ALT must be less than 2.5 x ULN for the lab. Adequate renal function within 28 days before study entry defined as serum creatinine less than or equal to 1.5 x ULN for the lab or measured or calculated creatinine clearance greater than or equal to 50 mL/min using the Cockroft-Gault formula for patients with creatinine levels greater than 1.5 x ULN for the lab. For Women Creatinine Clearance (mL/min) = (140
•age) x weight (kg) x 0.85 72 x serum creatinine (mg/dL) For Men Creatinine Clearance (mL/min) = (140
•age) x weight (kg) 72 x serum creatinine (mg/dL) HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Pregnancy test (urine or serum according to institutional standard) done within 14 days before study entry must be negative (for women of childbearing potential only). Patients receiving a coumarin-derivative anticoagulant must agree to weekly monitoring of INR if they are randomized to Arm 1 or Arm 3 and receive capecitabine. Eligibility Criteria for Cohort A Arm-2 patients on Second Randomization Patient must have developed a ctDNA +ve assay during serial monitoring. Patient's willingness to be re-randomized affirmed. The patient must continue to have an ECOG performance status of 0 or 1. No radiographic evidence of overt metastatic disease. Pregnancy test (urine or serum according to institutional standard) done within 14 days before study entry must be negative (for women of childbearing potential only). Adequate hematologic function within 28 days before randomization defined as follows:
• Absolute neutrophil count (ANC) must be greater than or equal to 1500/mm3;
• Platelet count must be greater than or equal to 100,000/mm3; and
• Hemoglobin must be greater than or equal to 9 g/dL. Adequate hepatic function within 28 days before randomization defined as follows:
• total bilirubin must be less than or equal to ULN (upper limit of normal) for the lab and
• alkaline phosphatase must be less than 2.5 x ULN for the lab; and
• AST and ALT must be less than 2.5 x ULN for the lab. Adequate renal function within 28 days before randomization defined as serum creatinine less than or equal to 1.5 x ULN for the lab or measured or calculated creatinine clearance greater than or equal to 50 mL/min using the Cockroft-Gault formula for patients with creatinine levels greater than 1.5 x ULN for the lab. For Women Creatinine Clearance (mL/min) = (140
•age) x weight (kg) x 0.85 72 x serum creatinine (mg/dL) For Men Creatinine Clearance (mL/min) = (140
•age) x weight (kg) 72 x serum creatinine (mg/dL)
Exclusion Criteria:
Colon cancer histology other than adenocarcinoma (i.e., neuroendocrine carcinoma, sarcoma, lymphoma, squamous cell carcinoma, etc.). Pathologic, clinical, or radiologic overt evidence of metastatic disease. This includes isolated, distant, or non-contiguous intra-abdominal metastases, even if resected. Tumor-related bowel perforation. History of prior invasive colon malignancy, regardless of disease-free interval. History of bone marrow or solid organ transplantation (regardless of current immunosuppressive therapy needs). Bone grafts, skin grafts, corneal transplants and organ/tissue donation are not exclusionary. Any prior systemic chemotherapy, targeted therapy, or immunotherapy; or radiation therapy administered as treatment for colorectal cancer (e.g., primary colon adenocarcinomas for which treatment with neoadjuvant chemotherapy and/or radiation is warranted are not permitted). Other invasive malignancy within 5 years before study entry. Exceptions are colonic polyps, non-melanoma skin cancer or any carcinoma-in-situ. Synchronous primary rectal and/ or colon cancers. Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better. Sensory or motor neuropathy greater than or equal to grade 2, according to CTCAE v5.0. Blood transfusion within two weeks before collection of blood for central ctDNA testing. Active seizure disorder uncontrolled by medication. Active or chronic infection requiring systemic therapy. Known homozygous DPD (dihydropyrimidine dehydrogenase) deficiency. Patients known to have Gilbert's Syndrome or homozygosity for UGT1A1*28 polymorphism. Pregnancy or lactation at the time of study entry. Co-morbid illnesses or other concurrent disease that would make the patient inappropriate for entry into this study (i.e., unable to tolerate 6 months of combination chemotherapy or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens or prevent required follow-up). Ineligibility Criteria for Cohort A Arm-2 patients on Second Randomization Pregnancy or lactation at the time of randomization. No longer a candidate for systemic chemotherapy (FOLFOX, CAPOX, and mFOLFIRINOX) in the opinion of the treating investigator.
Stage III Colon Cancer, Colon, Colon and Rectum
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Comparing the Addition of Radiation Either Before or After Surgery for Patients With Brain Metastases

This phase III trial compares the addition of stereotactic radiosurgery before or after surgery in treating patients with cancer that has spread to the brain (brain metastases). Stereotactic radiosurgery is a type of radiation therapy that delivers a high dose of radiation only to the small areas of cancer in the brain and avoids the surrounding normal brain tissue. Surgery and radiation may stop the tumor from growing for a few months or longer and may reduce symptoms of brain metastases.
Andrew Baschnagel, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05438212
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Inclusion Criteria:

• Radiographic confirmation of 1-4 brain metastases, one of which requires resection, as defined by magnetic resonance imaging (MRI) with contrast obtained within 14 days prior to registration
• The maximum diameter of the lesion to be resected on the post-contrast MRI, as measured on any orthogonal plane (axial, sagittal, coronal), must measure > 2.0 cm and < 5.0 cm.
• The maximum diameter of the lesions not to be resected must measure < 4.0 cm
• Known active or history of invasive non-central nervous system (CNS) primary cancer based on documented pathologic diagnosis within the past 3 years
• All brain metastases must be located > 5 mm from the optic chiasm and outside the brainstem
• Patient is able to medically tolerate surgery and SRS
• The lesion chosen for surgical therapy must be deemed an appropriate target for safe, gross total resection by the treating surgeon
• History/physical examination within 14 days prior to registration
• Age >= 18
• Karnofsky performance status (KPS) >= 60 within 14 days prior to registration
• A negative urine or serum pregnancy test (in persons of childbearing potential) within =< 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal for at least 12 consecutive months
• Participants who are sexually active must agree to use medically acceptable forms of contraception during treatment on this study to prevent pregnancy
• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
Exclusion Criteria:

• Prior cranial radiotherapy, including whole brain radiotherapy, or SRS to the resection site
• Note: The index lesion to be resected cannot have been previously treated with SRS (i.e. repeat radiosurgery to the same location/lesion is not allowed on this protocol). Previous SRS to other lesions is allowed
• Evidence of leptomeningeal disease (LMD)
• Note: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive cerebrospinal fluid (CSF) cytology and/or unequivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In that patient, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion
• Any medical conditions which would make this protocol unreasonably hazardous, including, but not limited to: contraindications to general endotracheal anesthesia; intracranial surgery; and stereotactic radiosurgery
• Primary histology of germ cell tumor, small cell carcinoma or lymphoma
• More than one brain metastasis planned for resection
• Inability to undergo MRI with contrast
• Planned administration of cytotoxic chemotherapy or tyrosine/multi-kinase inhibitors within the 3 days prior to, the day of, or within 3 days after the completion of SRS
• Note: chemotherapy and immunotherapy outside of this window are allowed
Metastatic Malignant Neoplasm in the Brain, Colon, Rectum, Lung, Breast, Prostate, Colon and Rectum
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Study to Assess Batoclimab in Participants With Active Thyroid Eye Disease

To evaluate the efficacy of batoclimab 680 milligrams (mg) subcutaneous (SC) once a week (QW) for 12 weeks followed by 340 mg SC QW for 12 weeks versus placebo on proptosis responder rate at Week 24.
Suzanne Van Landingham
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05517421
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Inclusion criteria:
• Are ≥18 years of age at screening.
• Have a clinical diagnosis of TED associated with active, moderate to severe TED with the following at screening and Visit 0:
• A CAS ≥ 4 in either eye, and
• Clinical evidence of worsened proptosis with: 1. Proptosis ≥ 18 mm and/or 2. Proptosis ≥ 3 mm increase from participant's baseline (prior to diagnosis of TED), as estimated by the Investigator/assessor
• Have moderate to severe active TED, as defined by European Group on Graves' Orbitopathy (EUGOGO) guidelines.
• Have onset of active TED within 12 months prior to screening.
• Have documented evidence of detectable anti-TSHR-Ab at screening.
• Are not expected to require immediate surgical intervention and are not planning corrective surgery/irradiation or medical therapy for TED during the course of the study.
• Are euthyroid with the baseline disease under control or have mild hypo- or hyperthyroidism. Additional inclusion criteria are defined in the protocol. Exclusion criteria:
• Have decreased best corrected visual acuity due to optic neuropathy.
• Have at least a 2-point decrease in CAS or ≥2 mm decrease in proptosis between screening and Baseline assessments in either eye.
• Have used any steroid (intravenous or oral) for the treatment of TED or other conditions within 4 weeks prior to screening.
• Have used any steroid (Intravenous or oral) with a cumulative dose equivalent to ≥ 1 g of methylprednisolone for the treatment of TED.
• Have known autoimmune disease other than TED, that, in the opinion of the Investigator, would interfere with the course and conduct of the study.
• Had previous orbital irradiation or surgery for TED. Additional exclusion criteria are defined in the protocol.
Thyroid Eye Disease, Eye Abnormalities [C11], Thyroid Diseases [C19], Other, Eye & Vision, Plastic & Reconstructive Surgery
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Comparison of Chemotherapy Before and After Surgery Versus After Surgery Alone for the Treatment of Gallbladder Cancer

This phase II/III trial compares the effect of adding chemotherapy before and after surgery versus after surgery alone (usual treatment) in treating patients with stage II-III gallbladder cancer. Chemotherapy drugs, such as gemcitabine and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy before surgery may make the tumor smaller; therefore, may reduce the extent of surgery. Additionally, it may make it easier for the surgeon to distinguish between normal and cancerous tissue. Giving chemotherapy after surgery may kill any remaining tumor cells. This study will determine whether giving chemotherapy before surgery increases the length of time before the cancer may return and whether it will increase a patient's life span compared to the usual approach.
Sam Lubner, MD
All
18 Years and over
Phase 2/Phase 3
This study is NOT accepting healthy volunteers
NCT04559139
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Inclusion Criteria:

• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Patient must have histologically-confirmed T2 or T3 gallbladder cancer discovered incidentally at the time of or following routine cholecystectomy for presumed benign disease
• NOTE: Patients with histologically-confirmed Tis, T1a, T1b, or T4 tumors are not eligible
• Patient must have undergone initial cholecystectomy within 12 weeks prior to randomization
• Patient must have the ability to understand and the willingness to sign a written informed consent document
• Leukocytes >= 3,000/mcL (obtained =< 28 days prior to randomization)
• Absolute neutrophil count >= 1,500/mcL (obtained =< 28 days prior to randomization)
• Platelets >= 100,000/mcL (obtained =< 28 days prior to randomization)
• Total bilirubin =< institutional upper limit of normal (ULN) except in patients with Gilbert's syndrome. Patients with Gilbert's syndrome are eligible if direct bilirubin < 1.5 x ULN of the direct bilirubin (obtained =< 28 days prior to randomization)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (obtained =< 28 days prior to randomization)
• Serum creatinine =< institutional ULN OR creatinine clearance >= 50 mL/min/1.73 m^2 (Based on Cockcroft Gault estimation) (obtained =< 28 days prior to randomization)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification. To be eligible for this trial, patients should be class 2B or better
Exclusion Criteria:

• Patient must not have any evidence of metastatic disease or inoperable loco-regional disease based on high-quality, preoperative, cross-sectional imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) of the chest, abdomen, and pelvis (C/A/P) obtained within 6 weeks prior to randomization, defined as
• No radiographic evidence of distant disease (M1 disease)
• No radiographic evidence of tumor invasion into multiple extrahepatic organs (T4 disease)
• No radiographic evidence of distant lymph node involvement (celiac, para-aortic, para-caval lymph nodes)
• No evidence of new-onset ascites
• Soft tissue thickening within or in direct communication with the gallbladder fossa, peri-portal lymph node involvement, involvement of one extrahepatic organ, and other disease within the confines of what constitutes 'localized resectable' disease are allowable
• Women must not be pregnant or breast feeding due to the potential harm to unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All females of child bearing potential must have a serum or urine pregnancy test to rule out pregnancy within 14 days prior to randomization. A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
• Women of childbearing potential and sexually active males must not expect to conceive or father children by being strongly advised to use accepted and effective method(s) of contraception or to abstain from sexual intercourse for the duration of their participation in the study
Stage II Gallbladder Cancer AJCC v8, Stage IIA Gallbladder Cancer AJCC v8, Stage IIB Gallbladder Cancer AJCC v8, Stage III Gallbladder Cancer AJCC v8, Stage IIIA Gallbladder Cancer AJCC v8, Stage IIIB Gallbladder Cancer AJCC v8, Other Digestive Organ, Gastrointestinal cancers, other
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Trial of Pre-operative Neratinib and Endocrine Therapy With Trastuzumab in ER-Positive, HER-2 Positive Breast Cancers

Patient will be treated with neratinib, an aromatase inhibitor and trastuzumab for 24 weeks prior to surgery, following an initial 3 weeks of neratinib alone, aromatase inhibitor alone or the combination of neratinib and an aromatase inhibitor. A breast biopsy will be performed prior to Day 1 of week 4 of treatment. Following surgery, patients will receive standard of care HER2-directed and endocrine therapy at the treating physician's discretion.
Kari Wisinski, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT04886531
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Inclusion Criteria:
Subject must meet all of the following applicable inclusion criteria to participate in this study:
• Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• Postmenopausal females. NOTE: Postmenopausal status defined as: prior bilateral oophorectomy, Age ≥ 60 years, or Age < 60 years and amenorrhea for 12 or more months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) or an estradiol level in postmenopausal ranges per local reference range.
• ECOG Performance Status of 0-2 within 28 days prior to registration.
• Anatomic, clinical stage I-III, invasive breast cancer, greater than 10mm
• HER2-positive (by the most recent ASCO-CAP criteria)
• ER positive (≥ 10%). NOTE: There is no requirement for PR status; PR positive or negative allowed.
• Resectable breast cancer in which pre-operative therapy is appropriate (T > 10mm and/or node-positive).
• Archival tissue from the diagnostic pre-treatment biopsy is required. This sample should be identified at screening and shipped by Week 4. If archival tissue is not available, the subject is not eligible for the study.
• Agreeable to repeat breast biopsy at 3 weeks after initiation of treatment.
• Candidate for either letrozole or anastrozole, as determined by the treating physician
• Left ventricular ejection fraction (LVEF) ≥ 50% as assessed by echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) documented within 4 weeks prior to the study treatment.
• Demonstrate adequate organ function as defined below; all screening labs to be obtained within 28 days prior to registration.
• Hematological
• Platelet count ≥100,000/uL
• Absolute Neutrophil Count (ANC) ≥1500/uL
• Hemoglobin (Hgb) ≥10 g/dL
• Renal ---Calculated creatinine clearance: CrCl ≥60 mL/min using the Cockcroft-Gault formula
• Hepatic
• Bilirubin ≤1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) ≤ 2.5 × ULN
• Alanine aminotransferase (ALT) ≤ 2.5 × ULN
• HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial.
• For patients with known serologic evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, the HCV viral load must be undetectable to be eligible for this trial.
• Ability of the subject to understand and comply with study procedures for the entire length of the study, as determined by the enrolling physician or protocol designee.
Exclusion Criteria:
Subjects meeting any of the criteria below may not participate in the study:
• Locally advanced or inflammatory breast cancer.
• Evidence of metastatic disease. Systemic imaging is not required.
• Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are not eligible for this trial: exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least five years.
• Active infection requiring systemic therapy.
• Requirement for use of a moderate or stonr CYP3A4 inhibitor or inducer during the study (see protocol).
• Treatment with any investigational drug within 14 days prior to registration or within 5 half-lives of the investigational product, whichever is longer.
• Subject has had major surgery within 14 days prior to registration or has not recovered from major side effects of the surgery (tumor biopsy is not considered as major surgery).
• Any impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) or significantly impair the ability to swallow capsules/tablets.
• Known history of myelodysplastic syndrome or acute myeloid leukemia.
• Subjects with any of the following conditions:
• History of abdominal fistula, gastrointestinal perforation, or intra- abdominal abscess within 28 days prior to registration.
• Any history of cerebrovascular accident (CVA) or transient ischemic attack within 12 months prior to registration.
• History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 6 months prior to registration.
• Symptomatic congestive heart failure (New York Heart Association III-IV) or documented current cardiomyopathy with left ventricular ejection fraction (LVEF) <50%.
• Clinically significant cardiac ventricular arrhythmias (e.g. sustained ventricular tachycardia/ventricular fibrillation) or high-grade AV block (e.g. bifascicular block, Mobitz type II and third-degree AV block) unless a pacemaker is in place.
• Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome.
• Any concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate subject participation in the clinical study or compromise compliance with the protocol.
Breast Cancer, HER2-positive Breast Cancer, ER Positive Breast Cancer, PR-Positive Breast Cancer, Breast
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Testing the Safety and Effectiveness of Radiation-based Treatment (Lutetium Lu 177 Dotatate) for Metastatic Prostate Cancer That Has Neuroendocrine Cells

This phase II trial studies how well lutetium Lu 177 dotatate works in treating patients with prostate cancer with neuroendocrine differentiation that has spread to other places in the body (metastatic). Neuroendocrine differentiation refers to cells that have traits of both hormone-producing endocrine cells and nerve cells. These cells release hormones into the blood in response to a signal from the nervous system. Hormones are biological substances that circulate through the bloodstream to control the activity of other organs or cells in the body. Lutetium Lu 177-dotate is a radioactive drug. It binds to a protein called somatostatin receptor, which is found on some neuroendocrine tumor cells. Lutetium Lu 177-dotatate builds up in these cells and gives off radiation that may kill them. It is a type of radioconjugate and a type of somatostatin analog. Treatment with Lutetium Lu 177 dotatate may shrink the tumor in a way that can be measured in patients with metastatic prostate cancer with neuroendocrine differentiation.
John Floberg, Assistant Professor
Male
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05691465
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Inclusion Criteria:

• Patients must have metastatic prostate cancer with neuroendocrine differentiation, as determined by at least one of the following:
• Histologically confirmed small cell or neuroendocrine cancer from a primary prostate or metastatic biopsy. Neuroendocrine prostate cancer includes mixed small cell with adenocarcinoma histology, as well as small or large cells with positive neuroendocrine markers (e.g., chromogranin or synaptophysin)
• Prostate adenocarcinoma with molecular features of neuroendocrine differentiated cancer (e.g., 2 of the following 3: PTEN, TP53, or RB loss)
• Progression of visceral metastases in the absence of PSA progression
• Serum chromogranin A > 5x normal limit, or neuron-specific enolase > 2x normal
• Age >= 18 years. Prostate cancer is typically a disease of older men, with the average age at diagnosis being 65 years. Consequently, because the research topic is not relevant to children, no children will be included in this study. There is no upper limit to the age of participants eligible for this study
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Absolute neutrophil count (ANC) >= 1,500/mcL
• Platelets >= 100,000/mcL
• Hemoglobin >= 8 g/dL, prior to each dose of lutetium lu 177 dotatate
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/ alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN
• Creatinine Cockcroft calculated creatinine clearance of >= 60 mL/min OR
• Glomerular filtration rate (GFR) of 60 mL/min/1.73 m^2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m^2
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
• Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Patients should be New York Heart Association Functional Classification of class 2B or better
• Current disease progression according to PCWG3 criteria
• Ongoing use of luteinizing hormone-releasing hormone (LHRH) agonists/antagonists will be required (unless prior bilateral orchiectomy or pure neuroendocrine carcinoma histology) to maintain testosterone at castrate levels. Patients with a pure neuroendocrine carcinoma histology do not need to be undergoing LHRH agonist/antagonist therapy
• No concurrent use of other anti-cancer therapies
• Pregnancy Precaution: The effects of lutetium lu 177 dotatate on the developing human fetus are unknown. For this reason and because radionuclides are known to be teratogenic, male participants and their female partners must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while her male partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of lutetium lu 177 dotatate administration. Patients must not donate sperm during the study and for 3 months after the last study drug administration
• Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity who have a legally-authorized representative (LAR) and/or family member available will also be eligible
• Patients will undergo a Gallium 68 Dotatate PET scan after enrollment. The Gallium 68 Dotatate PET must be positive to proceed with lutetium Lu 177 dotatate therapy. A positive scan will be defined as at least one lesion with an maximum standardized uptake value (SUVmax) > the average standardized uptake value (SUV) of normal liver. The positive lesion(s) can be in any location (bone metastases or visceral metastases). Patients with only bone metastases will be allowed
Exclusion Criteria:

• Patients who are receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Lutetium Lu 177 dotatate
• As per the Food and Drug Administration (FDA) package insert for Lutetium Lu 177 dotatate, use of long-acting somatostatin analogs (e.g., long-acting octreotide) is prohibited within 4 weeks prior to initiating Lutetium Lu 177 dotatate and during treatment. Use of short-acting somatostatin analogs is prohibited within 24 hours prior to initiating Lutetium Lu 177 dotatate and during treatment. Long-acting somatostatin analogs or short-acting somatostatin analogs will be allowed if the patient has a history of carcinoid syndrome and requires long-acting or short-acting somatostatin analogs for the control of his functional syndrome
• Patients with uncontrolled intercurrent illness
• Any of the following within 6 months before starting treatment: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft; congestive heart failure New York Heart Association (NYHA) Class III or IV
• Uncontrolled hypertension as indicated by a systolic blood pressure >= 160 mmHg or diastolic blood pressure >= 100 mmHg at screening
Metastatic Prostate Adenocarcinoma With Neuroendocrine Differentiation, Metastatic Prostate Neuroendocrine Carcinoma, Metastatic Prostate Small Cell Neuroendocrine Carcinoma, Stage IV Prostate Cancer AJCC v8, Prostate
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Targeted Therapy Directed by Genetic Testing in Treating Patients With Locally Advanced or Advanced Solid Tumors, The ComboMATCH Screening Trial

This ComboMATCH patient screening trial is the gateway to a coordinated set of clinical trials to study cancer treatment directed by genetic testing. Patients with solid tumors that have spread to nearby tissue or lymph nodes (locally advanced) or have spread to other places in the body (advanced) and have progressed on at least one line of standard systemic therapy or have no standard treatment that has been shown to prolong overall survival may be candidates for these trials. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with some genetic changes or abnormalities (mutations) may benefit from treatment that targets that particular genetic mutation. ComboMATCH is designed to match patients to a treatment that may work to control their tumor and may help doctors plan better treatment for patients with locally advanced or advanced solid tumors.
Nataliya Uboha, MD
All
Not specified
Phase 2
This study is NOT accepting healthy volunteers
NCT05564377
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Inclusion Criteria:

• Patient must have measurable disease
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status between 0-2 OR patient must have Lansky performance status of >= 50% or Karnofsky performance status of >= 50%
• Patient must be deemed potentially eligible for a ComboMATCH Treatment Trial as assessed by the enrolling provider
• All patients must have sequencing results available from a National Cancer Institute (NCI) credentialed Designated Laboratory (DL)
• Patients must have locally advanced or advanced histologically documented solid tumors requiring therapy and meet one of the following criteria:
• Patients must have progressed on at least one line of standard systemic therapy OR
• Patients whose disease has no standard treatment that has been shown to prolong overall survival
• Patient must meet one of the following requirements:
• Patients 18 years and older who have tumor amenable to minimal risk image-guided or direct vision biopsy and must be willing and able to undergo a tumor biopsy to obtain samples for research if the patient is to enroll in a ComboMATCH treatment trial OR
• Patients 18 years and older who do not have disease that is biopsiable at minimal risk to the patient must confirm availability of an archival tumor tissue specimen for submission for research if the patient enrolls to a ComboMATCH Treatment Trial. This tumor tissue must meet the following criteria:
• Tissue must have been collected within 12 months prior to registration to the EAY191 Registration Trial
• Patient must not have had a Response Evaluation Criteria in Solid Tumors (RECIST) response (complete response [CR] or partial response [PR]) to any intervening therapy after collection of the tissue
• Formalin-fixed paraffin-embedded tumor tissue block(s) or slides must be available OR
• Patients under 18 years old must confirm availability of an archival tumor tissue specimen for submission for research if patient enrolls to a ComboMATCH Treatment Trial. This tumor tissue must meet the following criteria:
• Formalin-fixed paraffin-embedded tumor tissue block(s) or slides must be available
• NOTE: See specific ComboMATCH Treatment Trial protocol for tissue collection and management instructions. Performance of the mandatory research biopsy or submission of pre-trial formalin-fixed paraffin-embedded (FFPE) and collection and submission of the blood specimens for the integrated studies will be performed under the consent authority of the specific treatment trial protocol to which the patient is registered. No procedures to collect specimens for research only are to be performed for patients registered to the EAY191 Registration Trial only
• NOTE: Each ComboMATCH Treatment Trial contains specific eligibility criteria. If patient is found to not be eligible for the assigned ComboMATCH Treatment Trial, indication of ineligibility will trigger re-evaluation and potential assignment to another Treatment Trial
Advanced Malignant Solid Neoplasm, Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8, Locally Advanced Malignant Solid Neoplasm, Malignant Female Reproductive System Neoplasm, Metastatic HER2-Negative Breast Carcinoma, Metastatic Malignant Solid Neoplasm, Recurrent Endometrial Carcinoma, Recurrent Fallopian Tube Carcinoma, Recurrent Malignant Female Reproductive System Neoplasm, Recurrent Malignant Solid Neoplasm, Recurrent Ovarian Carcinoma, Recurrent Primary Peritoneal Carcinoma, Unresectable HER2-Negative Breast Carcinoma, Unresectable Malignant Solid Neoplasm, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
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Study of Chemotherapy Plus Ipatasertib for People With Solid Tumors With AKT Mutations, A ComboMATCH Treatment Trial

This phase II ComboMATCH treatment trial tests the usual treatment of chemotherapy (paclitaxel) plus ipatasertib in patients with solid tumor cancers that that cannot be removed by surgery (unresectable), has spread to nearby tissue or lymph nodes (locally advanced) or from where it first started (primary site) to other places in the body (metastatic), and has an AKT genetic change. Chemotherapy drugs, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Targeted therapy, such as Ipatasertib, may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. The addition of ipatasertib to paclitaxel in solid tumors with an AKT genetic change could increase the percentage of tumors that shrink as well as lengthen the time that the tumors remain stable (without progression). Researchers hope to learn if paclitaxel plus ipatasertib will shrink this type of cancer or stop its growth.
Nataliya Uboha, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05554380
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Inclusion Criteria:

• Patient must have enrolled onto EAY191 and must have been given a treatment assignment to ComboMATCH to EAY191-S3 based on the presence of an actionable mutation as defined in EAY191
• GENERAL COMBOMATCH EAY191 REGISTRATION INCLUSION CRITERIA:
• Participants must be enrolled on the ComboMATCH Master Registration Trial EAY191
• Participants must have an activating AKT mutation (a known mutation in AKT1, AKT2, or AKT3, a single nucleotide variant, insertion, or deletion) as determined by the ComboMATCH screening assessment
• GENERAL COMBOMATCH EAY191 REGISTRATION EXCLUSION CRITERIA:
• Participants must not have an activating KRAS, NRAS, HRAS, or BRAF mutation (a single nucleotide variant, insertion, or deletion) as determined by the ComboMATCH screening assessment
• Participants must have disease that can be safely biopsied and agree to a pre-treatment biopsy or have archival tissue available from within 12 months prior to the date of registration on the ComboMATCH Registration Trial (EAY191)
• Participants must have a histologically confirmed non-breast solid malignancy
• Participants must have locally advanced, unresectable, or metastatic disease in the opinion of the treating investigator
• Participants must have measurable disease documented by CT or MRI. Measurable disease must be assessed within 28 days prior to registration. Non-measurable disease must be assessed within 42 days prior to registration. The CT from a combined positron emission tomography (PET)/CT may be used only if it is of diagnostic quality. All known sites of disease must be assessed and documented on the Baseline Tumor Assessment Form (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1). Participants whose only measurable disease is within a previous radiation therapy port must demonstrate clearly progressive disease (in the opinion of the treating investigator) prior to registration
• Participants with known brain metastases must have a CT/MRI scan to evaluate for central nervous system (CNS) disease and show no evidence of progression within 42 days prior to registration
• Participants must have completed any CNS-directed therapy and/or local therapy for spinal cord compression at least 28 days prior to registration
• Participants must not have spinal cord compression or brain metastases unless: (1) metastases have been locally treated and have remained clinically controlled and asymptomatic for at least 14 days prior to registration, AND (2) participant has no residual neurological dysfunction and has been off corticosteroids for at least 24 hours prior to registration
• Participants must not have leptomeningeal disease
• Participants must have progressed within 6 months of taxane-based therapy in the neoadjuvant/adjuvant or metastatic setting
• Participants must not have received any prior AKT inhibitor (e.g., capivasertib or ipatasertib); prior PI3K/mTOR inhibitor is acceptable
• Participants must not be planning to receive any concurrent chemotherapy, immunotherapy, biologic, radiation, or hormonal therapy for cancer treatment while receiving treatment on this study
• Participants must be >= 18 years of age
• Participants must be able to swallow oral medications whole
• Participants must have a pre-study history and physical exam done within 28 days prior to registration
• Participants must have a Zubrod performance status of 0-2 within 28 days prior to registration
• Participants must have adverse events resolved =< grade 1 related to any prior therapy, except alopecia within 14 days prior to registration
• Participants with neuropathy must have resolved to < grade 2 within 14 days prior to registration
• Leukocytes >= 3 x 10^3/uL (within 28 days prior to registration)
• Absolute neutrophil count >= 1.5 x 10^3/uL (within 28 days prior to registration)
• Platelets >= 100 x 10^3/uL (within 28 days prior to registration)
• Total bilirubin =< institutional upper limit of normal (ULN) unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin =< 5 x institutional ULN (within 28 days prior to registration)
• Aspartate aminotransferase (AST) & alanine aminotransferase (ALT) =< 3 x institutional ULN (within 28 days prior to registration)
• Participants must have adequate cardiac function, class IIB (2B) or better. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification
• Participants must have a measured OR calculated creatinine clearance >= 50 mL/min using the following Cockcroft-Gault formula. This specimen must have been drawn within 28 days prior to registration
• Participants with known human immunodeficiency virus (HIV)-infection must be receiving anti-retroviral therapy and have an undetectable viral load test on the most recent test results obtained within 6 months prior to registration
• Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load on suppressive therapy within 28 days prior to registration
• Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with HCV infection who are currently on treatment must have an undetectable HCV viral load within 28 days prior to registration
• Participants must have an electrocardiography (ECG) performed (if clinically indicated with a corrected QTc interval of =< 470 msec) within 28 days prior to registration
• Participants must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to ipatasertib and/or paclitaxel
• Participants must not have an active small/large bowel inflammation such as ulcerative colitis or Crohn's disease
• Participants must not have grade 2 or higher uncontrolled intercurrent illness
• NOTE: To receive an agent, participant must not have any uncontrolled intercurrent illness requiring antibiotic/antiviral/antifungal therapy or interventional procedures. Participants with infections unlikely to be resolved within 2 weeks following registration should not be considered for the trial
• Participants must not have a known grade 2 or higher uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia
• Participants must not have any of the following:
• Cirrhosis at a level of Child-Pugh B (or worse),
• Cirrhosis (any degree) and a history of hepatic encephalopathy, or
• Clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis
• Participants must not be receiving any medications or substances that are inhibitors or inducers of CYP3A. Treatment with strong CYP3A inhibitors or strong CYP3A inducers within 2 weeks or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study drug is prohibited.
• NOTE: Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product. The participant wallet card should be presented to the participant
• Participants must not have baseline fasting glucose (after 8-hour fast) > 160 mg/dL (8.9 mmol/L) within 28 days prior to registration
• Participants with known diabetes mellitus must not require insulin therapy or have a baseline fasting glucose >150 mg/dL (8.3 mmol/L) or high glycosylated hemoglobin (Hb)A1c, (>= 8.0%), suggesting poorly controlled diabetes
• Participants who are on a stable dose of oral diabetes medication >= 2 weeks prior to initiation of study drug treatment are eligible for enrollment
• Participants with a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) must not have a potential to interfere with the safety or efficacy assessment of the investigational regimen
• Participants must not have lung disease requiring active systemic therapy or placing participants at increased risk of toxicity related to study-directed therapy including, but not limited to pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, aspergillosis, active tuberculosis, or history of opportunistic infections (pneumocystis pneumonia or cytomegalovirus pneumonia)
• Participants must not be pregnant or nursing. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is of "reproductive potential". In addition to routine contraceptive methods, "effective contraception" also includes surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
• Participants must not have psychiatric illness/social situations that would limit compliance with study requirements
Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus, Locally Advanced Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm, Unresectable Malignant Solid Neoplasm
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Study Transplanting Bone Marrow Cells Into Salivary Glands to Treat Dry Mouth Caused by Radiation Therapy

The goal of this clinical research study is to evaluate the safety and tolerability of injecting certain cells that you produce in your bone marrow called mesenchymal stem cells (MSCs) into your salivary glands. Participants will have head and neck cancer that was treated with radiation therapy, and in this study will: - Undergo a collection of bone marrow using a needle; - Donate saliva; - Undergo a salivary gland ultrasound; and, - Complete questionnaires that ask about dry mouth Participants can expect to be in this study for up to 30 months.
Randall Kimple, MD, PhD
All
18 Years to 90 Years old
Phase 1
This study is NOT accepting healthy volunteers
NCT05820711
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Inclusion Criteria:

• History of histological diagnosis of head and neck cancer (HNC) that was treated with radiation therapy and currently clinically or radiologically no evidence of disease (NED)
• Xerostomia, defined as patient reported salivary function (pre-treatment) ≤ 80% of healthy (pre-radiation)
• ≥ 18 years of age, ≤ 90 years of age.
• Patients ≥ 2 years from completion of radiation therapy for HNC
• Karnofsky performance status ≥ 70, patient eligible for bone marrow aspirate with wakeful anesthesia
• Willing and able to give informed consent
• Radiographically confirmed submandibular gland(s)
Exclusion Criteria:

• Salivary gland disease (i.e., sialolithiasis)
Head and Neck Cancer, Xerostomia, Lip, Oral Cavity and Pharynx, Larynx, Head and Neck
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ONC201 in H3 K27M-mutant Diffuse Glioma Following Radiotherapy (the ACTION Study) (ACTION)

This is a randomized, double-blind, placebo-controlled, parallel-group, international, Phase 3 study in patients with newly diagnosed H3 K27M-mutant diffuse glioma to assess whether treatment with ONC201 following frontline radiotherapy will extend overall survival and progression-free survival in this population. Eligible participants will have histologically diagnosed H3 K27M-mutant diffuse glioma and have completed standard frontline radiotherapy.
Ankush Bhatia, M.D.
All
Not specified
Phase 3
This study is NOT accepting healthy volunteers
NCT05580562
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Inclusion Criteria:
1. Able to understand the study procedures and agree to participate in the study by providing written informed consent (by participant or legally authorized representative), and assent when applicable. 2. Body weight ≥ 10 kg at time of randomization. 3. Histologically diagnosed H3 K27M-mutant diffuse glioma (new diagnosis). Detection of a missense K27M mutation in any histone H3-encoding gene detected by testing of tumor tissue (immunohistochemistry [IHC] or next-generation sequencing [NGS] in a Clinical Laboratory Improvement Amendments [CLIA]-certified or equivalent laboratory). [Site to provide (as available): ≥ 10 unstained formalin-fixed paraffin-embedded (FFPE) slides from tumor tissue.] 4. At least one, high-quality, contrast-enhanced MRI of the brain obtained prior to starting radiotherapy for submission to sponsor's imaging vendor for central read. For participants who had a surgical resection, this scan must be post-resection; for participants who did not have a resection, this scan may be pre- or post-biopsy. 5. At least one, high-quality, contrast-enhanced MRI of the brain obtained 2 to 6 weeks after completion of frontline radiotherapy. If unable to obtain contrast-enhanced imaging due to lack of venous access after multiple attempts, a patient may still be eligible after collection of a nonenhanced MRI of the brain. [Site to also provide all available MRIs completed prior to initiating treatment with study intervention.] 6. Received frontline radiotherapy 1. Initiated radiotherapy within 12 weeks from the initial diagnosis of H3 K27M-mutant diffuse glioma. 2. Completed radiotherapy within 2 to 6 weeks prior to randomization 3. Completed standard fractionated radiotherapy (eg. 54 to 60 Gy in 28 to 33 fractions given over approximately 6 weeks or hypofractionated radiotherapy (eg. 40 Gy in 15 fractions given over approximately 3 weeks). 7. Karnofsky Performance Status or Lansky Performance Status ≥ 70 at time of randomization. 8. Stable or decreasing dose of corticosteroids and anti-seizure medications for 7 days prior to randomization, if applicable. Stable steroid dose is defined as ≤ 2 mg/day increase (based on dexamethasone dose or equivalent dose of an alternative steroid).
Exclusion Criteria:
1. Primary spinal tumor. 2. Diffuse intrinsic pontine glioma (DIPG), defined as tumors with a pontine epicenter and diffuse involvement of the pons. 3. Evidence of leptomeningeal spread of disease or cerebrospinal fluid dissemination. 4. Any known concurrent malignancy. 5. New lesion(s) outside of the radiation field. 6. Received whole-brain radiotherapy. 7. Received proton therapy for glioma. 8. Use of any of the following treatments within the specified time periods prior to randomization: 1. ONC201 or ONC206 at any time. 2. Systemic bevacizumab (includes biosimilars) at any time since the initial diagnosis of H3 K27M-mutant diffuse glioma. 3. Temozolomide within past 3 weeks. 4. Tumor treating fields at any time. 5. DRD2 antagonist within past 2 weeks. 6. Any investigational therapy within past 4 weeks. 7. Strong CYP3A4 inhibitors within 3 days. 8. Strong CYP3A4 inducers (includes enzyme-inducing antiepileptic drugs) within 2 weeks. 9. Laboratory test results meeting any of the following parameters within 2 weeks prior to randomization: 1. Absolute neutrophil count < 1.0 × 109/L or platelets < 75 × 109/L. 2. Total bilirubin > 1.5 × upper limit of normal (ULN) (participants with Gilbert's syndrome may be included with total bilirubin > 1.5 × ULN if direct bilirubin is ≤ 1.5 × ULN). 3. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × ULN. 4. Creatinine clearance ≤ 60 mL/min as calculated by the Cockcroft Gault equation (or estimated glomerular filtration rate < 60 mL/min/1.73 m2). 10. QTc > 480 msec (based on mean from triplicate electrocardiograms) during screening. 11. Known hypersensitivity to any excipients used in the study intervention formulation. 12. Pregnant, breastfeeding, or planning to become pregnant while receiving study intervention or within 3 months after the last dose. Participants of childbearing potential must have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study intervention. 13. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring systemic therapy or psychiatric illness/social situations that would limit compliance with study requirements. 14. Any other condition (eg, medical, psychiatric, or social) that, in the opinion of the investigator, may interfere with participant safety or the ability to complete the study according to the protocol.
Brain and Nervous System, Brain/Central Nervous System, H3 K27M, Glioma
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Brightline-2: A Study to Test Whether Brigimadlin (BI 907828) Helps People With Cancer in the Biliary Tract, Pancreas, Lung or Bladder

This study is open to adults with advanced cancer in the biliary tract, pancreas, lung, or bladder. This is a study for people for whom previous treatment was not successful or no treatment exists. The purpose of this study is to find out whether a medicine called BI 907828 helps people with cancer in the biliary tract, pancreas, lung, or bladder. BI 907828 is a so-called MDM2 inhibitor that is being developed to treat cancer. All participants take BI 907828 as a tablet once every 3 weeks. Participants may continue to take BI 907828 as long as they benefit from treatment and can tolerate it. They visit the study site regularly. At the study site, doctors regularly check the size of the tumour and whether it has spread to other parts of the body. The doctors also regularly check participants' health and take note of any unwanted effects.
Jeremy Kratz, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05512377
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Inclusion Criteria:

• Diagnosis of a solid tumour which meets the criteria for an open trial cohort:
• Cohorts 1 and 1-CN (biliary tract adenocarcinoma): Locally advanced or metastatic biliary tract adenocarcinoma (intra- and extrahepatic cholangiocarcinoma, gallbladder cancer, and ampullary cancer).Patients must have unresectable disease and have received all available conventional therapies known to confer clinical benefit for their disease based on local approved standards; or (in the opinion of the investigator) patients are unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy.
• Cohort 2 (pancreatic ductal adenocarcinoma): Locally advanced or metastatic pancreatic ductal adenocarcinoma. Patients must have unresectable disease and have received all available conventional therapies known to confer clinical benefit for their disease based on local approved standards.
• Cohort 3 (lung adenocarcinoma): Locally advanced or metastatic lung adenocarcinoma. Patients must have unresectable disease and have received all available conventional therapies known to confer clinical benefit for their disease based on local approved standards.
• Cohort 4 (urothelial bladder cancer): Locally advanced or metastatic urothelial bladder cancer. Patients must have unresectable disease and have received all available conventional therapies known to confer clinical benefit for their disease based on local approved standards.
• Written pathology report / molecular profiling report indicating Mouse double minute 2 homolog (MDM2) amplification or a copy number ≥8 and tumor protein 53 (TP53) wild-type status. This must have been confirmed with a tissue-based test. A test with liquid biopsy is not accepted.
• Archival tissue (formalin fixed paraffin embedded [FFPE] tumour blocks or slides) must be provided for retrospective confirmation of MDM2 amplification and TP53 status.
• Presence of at least 1 measurable target lesion according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Patient must be willing to donate mandatory blood samples for the pharmacokinetics, pharmacodynamics, and biomarker analyses
• Adequate organ function
• All toxicities related to previous anti-cancer therapies have resolved to ≤Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 prior to trial treatment administration (except for alopecia and amenorrhea / menstrual disorders which can be of any grade and peripheral neuropathy which must be ≤CTCAE Grade 2).
• Life expectancy ≥3 months at the start of treatment in the opinion of the investigator.
• Provision of signed and dated, written informed consent form (ICF) in accordance with ICH-GCP and local legislation prior to any trial-specific procedures, sampling, or analyses.
• Male or female patients ≥18 years old at the time of signature of the ICF. Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use 2 medically acceptable methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly beginning at screening, during trial participation, and until 6 months and 12 days after last dose for women and 102 days after last dose for men. A list of contraception methods meeting these criteria is provided in the patient information.
Exclusion Criteria:

• Previous administration of brigimadlin (BI 907828) or any other MDM2-p53 or mouse double minute 4 (MDMX, MDM4)-p53 antagonist.
• Active bleeding, significant risk of haemorrhage (e.g. previous severe gastrointestinal bleeding, previous haemorrhagic stroke at any time), or current bleeding disorder (e.g. haemophilia, von Willebrand disease).
• Major surgery (major according to the investigator's assessment) performed within 4 weeks prior to start of trial treatment or planned within 6 months after screening (e.g. hip replacement).
• Clinically significant previous or concomitant malignancies in the opinion of the investigator affecting the efficacy and/or outcome of the trial.
• Patients who must or intend to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial.
• Currently enrolled in another investigational device or drug trial.
• Any history of, or concomitant condition that, in the opinion of the investigator, would compromise the patient's ability to comply with the trial or interfere with the evaluation of the safety and efficacy of the trial drug.
• Patients not expected to comply with the protocol requirements or not expected to complete the trial as scheduled (e.g. chronic alcohol or drug abuse or any other condition that, in the investigator's opinion, makes the patient an unreliable trial participant). Further exclusion criteria apply.
Pancreatic Neoplasms, Solid Tumors, Biliary Tract Cancer, Lung Neoplasms, Bladder Cancer, Liver, Lung, Prostate, Urinary Bladder, Bladder
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Evaluation of VX-121/Tezacaftor/Deutivacaftor in Cystic Fibrosis (CF) Participants 1 Through 11 Years of Age

The purpose of this study is to evaluate the pharmacokinetics, safety, tolerability and efficacy of VX-121/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA) in CF participants with at least 1 triple combination responsive (TCR) mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
Hara Levy, MD
All
1 Year to 11 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT05422222
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Key
Inclusion Criteria:

• Participants with stable CF and at least 1 TCR mutation (including F508del) in the CFTR gene Key
Exclusion Criteria:

• History of solid organ, hematological transplantation, or cancer
• Hepatic cirrhosis with portal hypertension, moderate hepatic impairment (Child Pugh Score 7 to 9), or severe hepatic impairment (Child Pugh Score 10 to 15)
• Lung infection with organisms associated with a more rapid decline in pulmonary status Other protocol defined Inclusion/Exclusion criteria may apply.
Cystic Fibrosis, Cystic fibrosis, Other, Lung & Respiratory
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A Randomized, Double-Blind, Placebo-Controlled Trial of IkT-148009 in Untreated Parkinson's Disease

This study investigates the safety and tolerability of drug IkT-148009 in untreated Parkinson's disease volunteers (30 to 80 years old). It also looks at the pharmacokinetics of IkT-148009 in the body and evaluates the effect of IkT-148009 on motor and non-motor features of the disease. This 12 week study is designed to be 3:1 randomized across 3 doses of IkT-148009 or placebo. Each participant will self-administer one of 3 doses or placebo of IkT-148009 once daily (QD) with food for 12 weeks. For more information, visit our website: www.the201trial.com
Kathleen Shannon
All
30 Years to 80 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT05424276
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Inclusion Criteria 1. Participants who are diagnosed with PD consistent with UK Brain Bank criteria and MDS Research Criteria; must include bradykinesia with sequence effect and motor asymmetry. 2. Receiving no anti-parkinsonian therapy 3. Modified Hoehn/Yahr Stage < 3.0 4. Montreal Cognitive Assessment ≥ 24 5. Patient expected to be able to participate in trial without need for additional anti-parkinsonian therapy Sex and Contraceptive/Barrier Requirements: 1. Male participants must agree to practice an acceptable method of highly effective birth control from the screening visit, while on study and for 30 days after receiving the last dose of study drug. Highly effective methods of birth control include sexual abstinence, vasectomy, or a condom with spermicide (men) in combination with their partner's highly effective method. 2. Female participants of childbearing potential and male participants with female partners of childbearing potential must agree to either remain abstinent or use adequate and reliable contraception throughout the study and at least 30 days after the last dose of study drug has been taken. Informed Consent: 1. Capable of giving signed ICF as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. Other Inclusions: 1. Approved as an appropriate and suitable candidate by the EAC. Exclusion Criteria 1. Diagnosis/suspicion of secondary or atypical parkinsonism 2. Previous procedure or surgery for PD, or anticipation of these during the study 3. High likelihood of needing anti-parkinsonian treatment over the study period, in the opinion of the investigator 4. Clinically significant orthostatic hypotension 5. Clinically significant hallucinations requiring antipsychotic use in the 12 months prior to Screening 6. Clinically significant medical, surgical, psychiatric, or laboratory abnormalities in the judgement of the treating investigator or the EAC Prior/Concomitant Therapy: 1. Past treatment with levodopa, dopaminergic agonists, monoamine oxidase-B inhibitors, supplements containing levodopa (i.e. Mucana pruriens), or A2A antagonists for more than 28 days, or treatment with any of these medications or supplements within 28 days prior to screening 2. Past treatment with irreversible monoamine oxidase-B inhibitors (e.g., selegiline) for more than 28 days; must be discontinued for at least 90 days before screening 3. Currently receiving moderate or strong Cytochrome P450 (CYP) 3A4/5 inducers or CYP3A4/5 inhibitors (except for topical administration) 4. Currently receiving any antipsychotic, metoclopramide, reserpine, or amphetamine. Prior/Concurrent Clinical Study Experience: 1. Current participation in another investigational clinical trial and/or receipt of any investigational medication within 90 days prior to screening 2. Previous randomization into this or another IkT-148009 study Diagnostic Assessments: 1. Active suicidal ideation within one year prior to screening visit, as determined by the Columbia Suicide Rating Scale (answer of "yes" on question 4 or 5) 2. Current diagnosis or history of substance abuse (excluding nicotine or caffeine) by Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria 3. Medical or recreational use of marijuana in the 3 months prior to the screening visit 4. Any social or behavioral reason that would preclude completion of the study, in the judgement of the investigator 5. Any skin condition that would interfere with obtaining adequate samples 6. Evidence of advanced, age-related macular degeneration (neovascular or geographic atrophy) or intermediate macular degeneration as defined by Beckman classification (Large drusen > 125 um and/or any AMD pigmentary abnormalities). Evidence of retina/choroid neovascularization from any cause. Evidence of central serous retinopathy. 7. Abnormal amylase and/or lipase at screening (may be repeated during screening period) 8. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than 2.5 times the upper limit of normal (ULN) 9. Significant renal impairment as determined by the following criteria:
• Creatinine clearance (CrCL) less than or equal to 60 mL/min for subjects < 65 years of age
• Creatine clearance (CrCL) greater than or equal to 55 mL/min and the absence of proteinuria or hematuria for subjects ≥ 65 years of age 10. Currently lactating, pregnant or planning on becoming pregnant during the study
Parkinson Disease, Other, Brain & Neurological
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