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FFNP-PET/MR Imaging of Progesterone Receptor Expression in Invasive Breast Cancer

The goal of this research is to test the accuracy of PET/MRI imaging with 18F-fluorofuranylnorprogesterone (FFNP) for measuring progesterone receptor (PR) expression in patients with invasive breast cancer. The hypothesis is that FFNP SUVmax from PET/MRI will correlate well against the semi-quantitative PR immunohistochemistry score.
Amy Fowler, M.D., Ph.D.
Female
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT03212170
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Inclusion Criteria:

• Women 18 years of age or older
• Diagnosis of biopsy-proven invasive breast cancer measuring at least 1.0 cm in diameter by any imaging modality
• Biopsy-proven PR-positive (N=23) or PR-negative (N=5) invasive breast cancer
• Undergoing diagnostic breast MRI ordered by the referring clinician for staging and extent of disease
Exclusion Criteria:

• Inability or unwillingness to provide informed consent to the study
• Participants currently undergoing neoadjuvant chemotherapy/endocrine therapy or those who have received chemotherapy/endocrine therapy within 6 months prior to the MRI
• Participants who have had neoadjuvant chemotherapy/endocrine therapy, surgical intervention, or radiation for the current biopsy-proven malignancy
• Participants with breast expanders
• Participants who are or might be pregnant or lactating
• Participant girth exceeds the bore of the PET/MRI scanner
• Participants with a contraindication to gadolinium based contrast agents, including allergy or impaired renal function (per University of Wisconsin Health Guidelines)
• Participants with a history of allergic reaction attributable to compounds of similar chemical or biologic composition to FFNP
• Participants in liver failure as judged by the patient's physician
• Participants with standard contraindications to MRI, including claustrophobia and metallic implants incompatible with MRI
• Participants requiring intravenous (IV) conscious sedation for imaging are not eligible; participants requiring mild, oral anxiolytics for the clinical MRI will be allowed to participate as long as the following criteria are met:
• The subject has their own prescription for the medication
• The informed consent process is conducted prior to the self-administration of this medication
• They come to the research visit with a driver
• Participants unable to lie prone for 30 minutes for imaging
Invasive Breast Cancer, Malignant neoplasms of breast, Breast
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FES Imaging to Optimize Tamoxifen for Metastatic Breast Cancer

Despite broad advancements in endocrine therapy for ERα+ breast cancer, resistance ultimately develops. A common driver of resistance are known ESR1 mutations that lead to constitutively active receptor signaling and transcriptional regulation that is always "turned on" despite the absence of estrogen. Patients with ESR1 mutations are expected to have decreased binding affinity for tamoxifen and thus may be underdosed on standard therapy. [18F]-fluoroestradiol Positron Emission Tomography/Computed tomography (FES-PET/CT) imaging is a novel functional imaging technique that can non-invasively measure ERα expression and inhibition in metastatic ERα+ breast cancer. The proposed a pilot study uses FES-PET/CT imaging to measure ERα blockade to determine the optimal dose of tamoxifen in patients with ESR1 mutations.
Kari Wisinski, MD
All
19 Years and over
Early Phase 1
This study is NOT accepting healthy volunteers
NCT04174352
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Inclusion Criteria:

• Participants must have histologically confirmed breast cancer that is metastatic or unresectable with the following:
• Estrogen receptor expression by immunohistochemistry greater than or equal to 10%
• ESR1 mutation identified using a Clinical Laboratory Improvement Amendments (CLIA) certified assay via tumor biopsy tissue or circulating free DNA (cfDNA)
• human epidermal growth factor receptor 2 (HER2) negative
• Participants must have measurable disease as defined by RECIST 1.1 or evaluable bone-only disease with at least one lesion measuring 10 mm or greater in size. Participants with liver-only disease are not eligible due to the inherent hepatic uptake related to the radiopharmaceutical's hepatobiliary route of elimination.
• Participants must have received at least 1 prior line of non-tamoxifen containing endocrine therapy in the metastatic setting or have had progression within 12 months of adjuvant non-tamoxifen endocrine therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (See Appendix A)
• Life expectancy of greater than 12 weeks.
• Ability to take oral medications.
• Informed consent: participant must be informed of the investigational nature of the study and must be able to sign a written informed consent.
• Participants with central nervous system (CNS) metastases must be stable after therapy for CNS metastases (such as surgery, radiation, or stereotactic radiosurgery) for at least 1 month.
• Participants must have adequate normal organ and bone marrow function as defined below:
• Absolute neutrophil count >/= 1,000/mcL
• Hemoglobin >/= 9.0 g/dL
• Platelets >/= 100,000/mcL
• Total bilirubin • AST (SGOT)/ ALT (SGPT) • Creatinine /= 50 mL/min
Exclusion Criteria:

• Participants must have received at least 1 prior line of non-tamoxifen containing endocrine therapy in the metastatic setting or have had progression either while taking or within 12 months of adjuvant non-tamoxifen endocrine therapy (i.e. on or within 12 months of an aromatase inhibitor).
• Prior chemotherapy, radiotherapy, targeted, immunotherapy or investigational therapy within 2 weeks or major surgery within 4 weeks of study enrollment or those who have not recovered (to grade ≤ 1 or baseline) from clinically significant adverse events due to agents administered more than 2 weeks earlier (alopecia and fatigue excluded).
• Participants must not be receiving an ER blocking endocrine therapy (includes fulvestrant, tamoxifen, toremifene, raloxifene) and must be off the agents for a minimum of 60 days prior to planned FES PET/CT to allow for adequate uptake of FES.
• History of allergic reactions attributed to compounds of chemical or biologic composition similar to those of tamoxifen or [18F]-fluoroestradiol.
• Peripheral neuropathy of severity greater than grade 1.
• Current optic nerve disorders, retinopathy, lattice degeneration, macular degeneration, retinal vascular disorder, or retinal tears of severity greater than grade 1.
• History of cerebellar disorders, ataxia, and uncontrolled seizures unless related to transient medical condition and in investigator's opinion is not an active medical issue.
• History of venous thrombosis/thromboembolic event, including pulmonary embolism and stroke.
• Have a heart-rate corrected QT interval (using Fridericia's formula) (QTcF) ≥ 470msec or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, chronic hypokalemia, family history of long QT interval syndrome).
• Are taking medications that are known to prolong the QT interval, unless they can be transferred to other medications ≥ 5 half-lives prior to dosing or unless the medications can be properly monitored during the study. If equivalent medication is not available, QTcF should be closely monitored.
• Tamoxifen has demonstrated vaginal bleeding, birth defects and fetal loss in pregnant women. Tamoxifen use during pregnancy may have a potential long-term risk to the fetus of a Diethylstilbestrol syndrome (DES)-like syndrome. Women of childbearing potential (WOCP) must not be pregnant (confirmed by a negative urine/serum pregnancy test within 14 days of tamoxifen treatment). In addition, a medically acceptable method of birth control must be used such as an intrauterine device (IUD), use of a double barrier method (condoms, sponge, diaphragm, or vaginal ring with spermicidal jellies or cream), or total abstinence during the study participation and for 3 months after last dose of study drug. Women who are postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) are not considered to be WOCP.
• Ongoing treatment with other investigational agents. Participants cannot be receiving concomitant chemotherapy, radiotherapy, experimental therapy or any other therapy not otherwise outlined by the trial for the purposes of anti-cancer treatment.
• History of uterine malignancy unless participant has had hysterectomy with no evidence recurrent disease for ≥ 3 years from definitive therapy.
• Concurrent malignancy except for the following:
• Basal cell or squamous cell skin cancer
• In situ cervical cancer
• The following medications are contraindicated or must be used with caution.
• Contraindicated:
• CYP2D6, CYP3A4, and CYP2C9 strong inhibitors
• CYP2D6, CYP3A4, and CYP2C9 strong inducers
• Use with caution:
• CYP2C9 sensitive substrates
• CYP2D6 moderate inhibitors or inducers
• CYP3A4 moderate inhibitors or inducers Note: Transdermal products designed for systemic delivery must be assessed for interaction potential. Topical products not designed to provide systemic delivery (including inhaled products, ophthalmologic products and transvaginal preparations) do not need to be considered. Contraindicated medications are not allowed. Participants taking these concurrent medications are ineligible unless they can discontinue or switch to alternative medications prior to initiation of study drug (at least 5 half-lives). Use with caution agents are permitted if a) discontinuation is not feasible or b) no acceptable alternatives are available as determined by the treating physician; however, caution should be used. Consider monitoring by symptoms, labs or drug levels and dose adjustments of the medication.
• Uncontrolled intercurrent clinically significant illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Breast, ERα+ Breast Cancer, ESR1 Gene Mutation
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OAR-Based, Dose Escalated SBRT With Real Time Adaptive MRI Guidance for Liver Metastases

Stereotactic Body Radiation Therapy (SBRT) is a noninvasive local therapy with proven efficacy in a number of solid tumor types. However, colorectal cancer (CRC) liver metastases have been shown to be particularly resistant to SBRT, and often are found to have significantly worse rates of control compared with other histologies. Higher SBRT dose was recently shown to improve local control in CRC pulmonary metastases, however, increasing dose delivery with SBRT has been limited based on the risk of toxicity to adjacent structures, and the ability to visualize them during treatment. This is particularly relevant in treating liver tumors, as tumor and small bowel movement can often make tumor targeting and organs-at-risk (OAR) avoidance especially difficult. MRI-guided SBRT for liver tumors is both safe and feasible and offers an as yet unprecedented opportunity to achieve the highest possible safe dose to liver tumors. The purpose of this trial is to identify a safe maximum tolerated dose level for MRI-guided SBRT treatment of bowel and liver metastases, respectively. Eligible participants will be on study for up to 12 months.
Michael Bassetti, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT04020276
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Inclusion Criteria:

• For Phase I trial, have a diagnosis of histologically confirmed or clinically suspected metastatic cancer to the liver; for Phase IB trial have have a diagnosis of histologically confirmed or clinically suspected metastatic CRC to the liver.
• Participant must be a candidate for SBRT to at least one intrahepatic lesion but no more than 6 intrahepatic lesions.
• Participant must be a candidate for treatment on the ViewRay treatment unit. Must be screened to rule out implants and devices that are not MRI compatible.
• Be willing and able to provide written informed consent.
• Participants may be chemotherapy-naïve or have had prior chemotherapy up to two weeks prior to study entry.
• No active central nervous system (CNS) metastatic disease. NOTE: Subjects with CNS involvement must meet all of the following to be eligible:
• At least 28 days from prior definitive treatment of their CNS disease by surgical resection, SBRT or Whole Brain Radiation Therapy (WBRT) at the time of registration
• AND asymptomatic and off systemic corticosteroids and/or enzyme-inducing antiepileptic medications for brain metastases for >14 days prior to registration.
• Demonstrate adequate organ function as defined in the following table; all screening labs should be performed within 28 days of SBRT treatment initiation.
• Platelet count greater than or equal to 50000 /µL
• Absolute Neutrophil Count (ANC) greater than or equal to 1000 /µL
• Hemoglobin (Hgb) greater than or equal to 8 g/dL or greater than or equal to 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
• Serum creatinine OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) Creatinine/Calculated creatinine clearance (CrCl) greater than or equal to 30 mL/min for subject with creatinine levels greater than 1.5 X institutional upper limit of normal (ULN)
• Bilirubin greater than or equal to 1. 5 × ULN OR direct bilirubin greater than or equal to ULN for participants with total bilirubin levels greater than 1.5 ULN
• Aspartate aminotransferase (AST) and ALT (SGPT) greater than or equal to 5 × ULN for subjects with liver metastases
• Alanine aminotransferase (ALT) greater than or equal to 2.5 × ULN, greater than or equal to 5 × ULN in setting of metastatic disease
• International Normalized Ratio (INR) or Prothrombin Time (PT) greater than or equal to 1.5 X ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Activated Partial Thromboplastin Time (aPTT) greater than or equal to 1.5 X ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• For participants enrolled on the liver dose escalation arm, screening labs must be consistent with Child Pugh class A unless therapeutic anticoagulation places them in Child Pugh B. In that case, trial entry or exclusion will be at the discretion of the treating physician.
• Have a performance status of 2 or less on the Eastern Cooperative Oncology Group (ECOG) performance scale.
• Life expectancy of > 12 weeks.
• Women of childbearing potential (WOCP) should have a negative urine or serum pregnancy test prior to initiation of radiation therapy. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• WOCP must not be pregnant or breast-feeding.
• WOCP must be willing to use an effective method of birth control such as an oral, implantable, injectable, or transdermal hormonal contraceptive, an intrauterine device (IUD), use of a double barrier method (condoms, sponge, diaphragm, or vaginal ring with spermicidal jellies or cream), or total abstinence for the duration of the radiotherapy and 60 days thereafter. NOTE: A person of childbearing potential is anyone (regardless of sexual orientation, gender identity, having undergone a tubal ligation, or remaining celibate by choice) who was born with a uterus and at least one ovary and meets both of the following criteria:
• Is post-menarcheal (i.e., has had at least one prior menses)
• Has not undergone a hysterectomy or bilateral oophorectomy or has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Participant is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
Exclusion Criteria:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the initiation of SBRT.
• History of a second invasive cancer in the last 3 years (except for appropriately treated low-risk prostate cancer, treated non-melanoma skin cancer, appropriately treated ductal carcinoma in situ or early stage invasive carcinoma of breast appropriately treated in situ/early stage cervical/endometrial cancer.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with follow up scans or visits.
• Has a primary tumor histology of germ cell tumor, leukemia, or lymphoma.
• Has a primary liver cancer such as cholangiocarcinoma or hepatocellular carcinoma.
• Has had prior radiation therapy that significantly overlaps with the liver.
• Has a diagnosis of Crohn's disease, ulcerative colitis, or scleroderma.
• Participants with Gilbert's disease or other primary disorders of bilirubin metabolism will not be allowed on the trial.
• Has pre-existing liver disease such that patients are classified as Child Pugh B or worse. If the participant is anti-coagulated such that their INR places them in the CP-B classification, exclusion or inclusion will be at the discretion of the treating physician.
• Pregnancy or women of childbearing potential and men who are sexually active and refuse to use medically acceptable forms of contraception.
• Participants with implanted hardware that would preclude MRIs.
Breast, Colon, Lung, Colon and Rectum, Liver Metastases, Stereotactic Body Radiation Therapy, MRI-guided Treatment
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Evaluation and Treatment of Iron Deficiency in Ovarian Cancer Patients

This study tests the hypothesis that IV iron sucrose infusions given to iron deficient ovarian cancer patients prior to debulking surgery can improve pre-operative iron stores and decrease transfusion of packed red blood cells in the peri-operative period. 21 participants at least 18 years of age with epithelial ovarian cancer of any stage requiring neoadjuvant chemotherapy and surgery will be enrolled. Participants will be on study for a period of up to 3 months.
Lisa Barroilhet, MD
Female
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT03933813
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Inclusion Criteria:

• Provide written informed consent.
• Has a diagnosis of true or functional iron deficiency without anemia within 30 days of treatment on this protocol
• Iron deficiency without anemia (normal Hgb >/= 11.6 g/dL but ferritin < 30 ng/mL)
• Functional iron deficiency without anemia (ferritin >30 ng/ml and iron saturation of <50%)
• Has a clinical diagnosis of suspected epithelial ovarian cancer based on imaging studies, exam findings and laboratory values
• Participants must be planning to receive neoadjuvant chemotherapy for their cancer diagnosis (NACT is defined as chemotherapy prior to debulking surgery)
• Participants must be planning to undergo surgery for their cancer diagnosis
• Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to administration of first dose of IV iron sucrose. WOCBP is defined as patients who retain their reproductive structures and are not menopausal (defined as > age 50 with no menses for at least 1 year)
• Participants of reproductive potential must agree to use effective birth control during study participation. Effective birth control is defined as any FDA approved contraceptive method
Exclusion Criteria:

• Currently taken any form of oral or intravenous iron therapy. Patients must have discontinued iron therapy > 30 days from study entry
• Current untreated or unstable heart disease
• History of iron induced hypersensitivity or allergy
• History of leukemia, lymphoma, or other myelodysplastic disorders
• Prior diagnosis of hemochromatosis or hemoglobinopathy (e.g. thalassemia)
• Any subject with immediate requirement for radiotherapy
• Concomitant enrollment in another clinical trial interfering with endpoints on this study
• Any medical condition which could compromise participation in the study according to the investigator's assessment
• Female patient who is pregnant or breast-feeding
• Patients unwilling or unable to comply with the protocol or unable to give informed consent
Epithelial Ovarian Cancer, Anemia, Iron Deficiency Anemia, Ovary
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Immunonutrition and Carbohydrate Loading Strategies in Breast Reconstruction

This study is designed to test the following hypothesis: patients undergoing immediate alloplastic and autologous breast reconstruction following mastectomy that receive preoperative immunonutrition will experience a reduction in wound complications in the 30-day postoperative period compared to a standard of care control group (retrospective chart review) of 264 (132 alloplastic + 132 autologous) consecutive breast reconstruction patients prior to 5/25/2018.
Katherine Gast
Female
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT03764943
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Inclusion Criteria:

• Medically cleared to undergo oncologic resection and breast reconstructive surgery (including associated anesthesia) at the University of Wisconsin Hospital
• Undergoing unilateral or bilateral immediate alloplastic or autologous breast reconstruction by Drs. Afifi, Garland, Gast, Michelotti, Poore, Rao, or Siebert
Exclusion Criteria:

• Pregnant or breast-feeding women
• Incarcerated women
• Males
• Individuals unable to give consent due to another condition such as impaired decision-making capacity
• Women with intolerance or allergy to any ingredients contained within the Impact Advanced Recovery formula that prevents safe consumption of this product.
• Impact Advanced Recovery is suitable for lactose intolerance, gluten-free, kosher, and halal diets.
• We will exclude individuals with galactosemia
• Women who are unable to take oral nutritional supplements
Wound Complication, Wound Heal, Complications Wound, Surgical Wound Infection, Surgical Site Infection, Breast Cancer, Mastectomy, Lymphedema, Breast
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Treatment of Cytomegalovirus (CMV) Infections With Viral-Specific T Cells

The present trial will consist of the treatment of 20 pediatric and adult Hematopoietic Stem Cell Transplantation (HSCT) recipients or immunocompromised participants diagnosed with opportunistic Cytomegalovirus (CMV) infections with virus-specific, antigen-selected T-cells. CMV-specific T-cells will be isolated from donor leukapheresis products using the CliniMACS® Prodigy. Prior studies on transfer of CMV specific T-cells have been shown to be safe and efficacious in the treatment of CMV infections. The main trial objective is to evaluate the feasibility and safety of CMV-specific T-cell transfer in adult and pediatric participants suffering from CMV infections or reactivation following HSCT or due to other immunocompromised states (e.g.; primary immunodeficiency, cytotoxic therapy). Participants will be followed for one year.
Inga Hofmann, M.D.
All
1 Month and over
Phase 1
This study is NOT accepting healthy volunteers
NCT03798301
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Inclusion Criteria:
1. Adult or pediatric patient suffering from CMV reactivation/infections following HSCT or due to other immunocompromised states (e.g.; primary immunodeficiency, cytotoxic therapy).
• CMV reactivation/viremia defined as positive (>500 copies/ml) CMV qPCR and/or
• Presence of symptoms secondary to CMV infection or evidence of invasive CMV infection (e.g. pneumonitis, colitis) AND
• Patients must have ONE OF THE FOLLOWING CRITERIA:
• Absence of an improvement of viral load after ≥ 14 days of antiviral therapy with ganciclovir, valganciclovir or foscarnet (decrease by at least 1 log, i.e. 10-fold), or
• New, persistent and/or worsening CMV-related symptoms, signs and/or markers of end organ compromise while on antiviral therapy with ganciclovir, valganciclovir or foscarnet, or
• Have contraindications or experience adverse effects of antiviral therapy with ganciclovir, valganciclovir or foscarnet, or
• Known resistance to ganciclovir and/or foscarnet based on molecular testing. 2. Recipients of an allogeneic HSCT must be 28 days after stem cell infusion at the time of T-cell transfer. 3. Written informed consent given by patient or legal representative. 4. Minimum patient age 1 month. 5. Minimum weight 7 lbs. 6. Female patients of childbearing age with negative pregnancy tests. 7. Patient Karnofsky/Lansky Performance Status >30%. 8. Donor eligible based on FACT infectious screening requirements.
Exclusion Criteria:
1. Patient with acute GVHD > grade 2 or active moderate or severe chronic GVHD at time of T-cell transfer 2. Patient receiving steroids (>1.0 mg/kg body weight (BW) prednisone equivalent) at the time of T-cell transfer 3. Patient received allogeneic HSCT less than 28 days prior to T-cell transfer 4. Patient treated with donor lymphocyte infusion (DLI) within 28 days prior to T-cell transfer 5. Patient treated with Thymoglobulin (ATG), Alemtuzumab or T-cell immunosuppressive monoclonal antibodies within 28 days. 6. Patient with organ dysfunction or failure as determined by Karnofsky (patients >16 years) or Lansky (patients ≤16 years) score ≤30% (Appendix 5) 7. Patients with CMV retinitis 8. Concomitant enrollment in another clinical trial with endpoints interfering with this study 9. Any medical condition which could compromise participation in the study according to the investigator's assessment 10. Known HIV infection 11. Female patient who is pregnant or breast-feeding, or adult of reproductive potential not willing to use an effective method of birth control during study treatment. Note: Women of childbearing potential must have a negative serum pregnancy test at study entry. 12. Patients unwilling or unable to comply with the protocol or unable to give informed consent. Donor Eligibility: The original donor will be the first choice as source of T cells. If the original donor is not available for donation (such as NMDP donor, cord blood unit, or related donor not available) of peripheral mononuclear cells or does not meet all donor eligibility criteria (including donor selection criteria based on University of Wisconsin
•Madison Standard Operating Procedures for the selection of allogeneic donors), alternative related donors will be selected, with preference for those who have full HLA matching in 6/6 loci over those with partial HLA matching (≥ 3/6 HLA loci). 1. All donors must be ≥ 18 years old, available, CMV IgG positive, eligible and capable of undergoing a single standard 2 blood volume leukapheresis. If original HSCT donor is not available, CMV IgG negative or ineligible, a CMV IgG positive fully matched or haploidentical family donor will be used. 2. Related donors must be at least partially HLA compatible, matching with recipient in at least 3/6 HLA loci (HLA-A, HLA-B and HLA-DRB1 will be considered for this). 3. Donors must be CMV IgG seropositive. 4. Donors must show CMV T-cell activation after incubation with MACS GMP PepTivator Peptide Pools of CMV pp65 before undergoing leukapheresis. 5. Donor must meet the criteria for donor selection defined in the Standard Operating Procedures of the University of Wisconsin Hospitals and Clinics Stem Cell Transplant Program and in FACT standards.
Anus, Any Site, Bones and Joints, Brain and Nervous System, Breast, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Hodgkin's Lymphoma, Ill-Defined Sites, Kaposi's Sarcoma, Kidney, Larynx, Leukemia, other, Lip, Oral Cavity and Pharynx, Liver, Lung, Lymphoid Leukemia, Melanoma, Skin, Multiple Myeloma, Mycosis Fungoides, Myeloid and Monocytic Leukemia, Non-Hodgkin's Lymphoma, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Hematopoietic, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Soft Tissue, Stomach, Thyroid, Unknown Sites, Urinary Bladder, Head and Neck, Gastrointestinal cancers, other, Colon and Rectum, Anal, Sarcoma, Melanoma/Skin cancer, Hematologic cancers, other, Uterus, Genitourinary cancers, other, Bladder, Brain/Central Nervous System, Endocrine cancers, Lymphoma, Leukemia, CMV Infection, Cytomegalovirus Infections, CMV Viremia, Opportunistic Infections
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ONC201 With and Without Methionine-Restricted Diet in Patients With Metastatic Triple Negative Breast Cancer

This phase II trial studies how well Akt/ERK inhibitor ONC201 (ONC201) with or without methionine-restricted (MR) diet works in treating participants with triple negative breast cancer that has spread to other places in the body or cannot be removed by surgery. ONC201 activates a process that leads to the death of a cell. ONC201 is able to target tumor cells to get rid of them, but does not affect normal cells. MR diet is a methionine-free amino acid modified medical food. The addition of an intermittent MR diet may enhance the activity of ONC201. Giving ONC201 and an MR diet may work better in treating participants with breast cancer.
Kari Wisinski, MD
Female
18 Years to 64 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT03733119
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Inclusion Criteria:

• Metastatic or unresectable TNBC (estrogen receptor [ER] < 1%, progesterone receptor [PR] < 1% and HER2 negative either by immunohistochemistry [IHC] or in situ hybridization method by American Society of Clinical Oncology [ASCO]-College of American Pathologists [CAP] guidelines)
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. within 28 days prior to registration
• Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately
• Any number of prior lines of systemic therapy for metastatic disease
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
• Prior cancer treatment, including radiotherapy, must be completed at least 14 days prior to registration and the subject must have recovered from all reversible acute toxic effects of the regimen to =< grade 1 or to baseline prior to initiation of that therapy. Grade 2 or higher exceptions include alopecia, up to grade 2 neuropathy, and other grade 2 AEs or lab values not constituting a safety risk in the opinion of the treating physician. This criteria does not apply to lab tests for normal organ and marrow function outlined below.
• No active central nervous system (CNS) metastatic disease; subjects with prior definitive treatment of their CNS disease by surgical resection, stereotactic body radiation therapy (SBRT) or whole-brain radiotherapy (WBRT) > 28 days ago will be eligible if asymptomatic and off systemic steroids
• Life expectancy of greater than 12 weeks
• Normal organ and marrow function as defined per protocol definitions
• Absolute neutrophil count (ANC) > 1.5 x 10^3/uL
• Platelet count >= 100 x 10^3/uL
• Hemoglobin >= 9 g/dL
• Total bilirubin < 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) ≤ 2.5 x ULN if participant has liver metastases, ≤5x ULN.
• Creatinine < ULN (institutional normal)
• Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration. NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), or they are naturally postmenopausal for at least 12 consecutive months
• Females of childbearing potential must be willing to abstain from heterosexual activity or must agree to use adequate contraception (hormonal or barrier method) for the duration of study participation and for 90 days after discontinuation of study treatment
• Ability of the subject to understand and comply with study procedures for the entire length of the study
• Able to swallow ONC201
• Be willing to discontinue vitamin and mineral supplements for the duration of the study if randomized to receive the methionine restricted diet
Exclusion Criteria:

• No prior therapy with TRAIL receptor agonists
• Active infection requiring systemic therapy. Patients with a known history of human immunodeficiency virus (HIV) must have a CD4 count >= the institutional lower limit of normal within 28 days prior to registration. Patients with HIV must also be on a stable antiretroviral regimen for >= 28 days before registration
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study)
• Known additional malignancy that is active and/or progressive requiring treatment; 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 three years
• Treatment with any investigational drug agent =< 14 days prior to registration or within 5 half-lives of that investigational product, whichever is longer
• Participant who has had major surgery =< 14 days prior to registration or has not recovered from major side effects of the surgery (tumor biopsy is not considered as major surgery)
• Known hypersensitivity to any of the excipients of ONC201
• Any impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
• 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 (e.g. chronic pancreatitis, chronic active hepatitis, active untreated or uncontrolled fungal, bacterial or viral infections, etc.)
• Participants who follow a vegan or vegetarian diet
Triple Negative Breast Cancer, Breast
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Hybrid Molecular Imaging of ER in Breast Cancer Patients With DCIS

This prospective, one-arm study which will enroll participants with biopsy-proven DCIS scheduled for diagnostic breast MRI for preoperative staging/extent of disease evaluation as part of standard of care. Eligible participants will be consented for participation in the research study which includes a directed breast PET/MRI with 18F-FES. 18F-FES uptake of the known malignancy will be measured on the PET/MRI examination using standardized uptake values (SUV) and tumor-to-normal tissue ratios.
Amy Fowler, M.D., Ph.D.
Female
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT03703492
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Inclusion Criteria:

• Diagnosis of biopsy-proven DCIS without invasion or microinvasion measuring at least 1.0 cm in diameter by any imaging modality
• Undergoing diagnostic breast MRI ordered by the referring clinician for staging and extent of disease
Exclusion Criteria:

• Inability or unwillingness to provide informed consent to the study
• Surgery, radiation, neoadjuvant chemo/endocrine therapy for the current malignancy prior to study enrollment
• Participants currently taking or have taken an ER-blocking medication (e.g. tamoxifen, raloxifene) within 6 weeks prior to study enrollment
• Pregnant or lactating women
• Participant with intolerance or contraindications for MRI or gadolinium-based contrast agents
• Participant girth exceeds the bore of the MRI/PET scanner
• Participants with a history of allergic reaction attributable to compounds of similar chemical or biologic composition to 18F-FES
• Participants in liver failure as judged by the patient's physician, due to the hepatobiliary clearance of 18F-FES
• Participants requiring intravenous (IV) conscious sedation for imaging are not eligible; participants requiring mild, oral anxiolytics for the clinical MRI will be allowed to participate as long as the following criteria are met:
• The participant has their own prescription for the medication
• The informed consent process is conducted prior to the self-administration of this medication
• They come to the research visit with a driver or an alternative plan for transportation (e.g. Uber, taxi, etc.)
Malignant neoplasms of breast, Breast Cancer, Ductal Carcinoma in Situ - Category
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Pharmacodynamic Biomarkers of Standard Anti-microtubule Drugs as Assessed by Early Tumor Biopsy

Eligible subjects will be assigned to study treatment arms by their treating oncologist, rather than by the study. The drug, dose, and schedule of administration will be determined by the treating physician per NCCN guidelines for standard of care chemotherapy regimens for recurrent or metastatic breast cancer. Study treatment arms include: Taxane (nab-paclitaxel or paclitaxel), Eribulin, Vinorelbine, Ixabepilone, or the control arm (non-microtubule targeted chemotherapies such as doxorubicin, carboplatin, or gemcitabine).
Mark Burkard, MD, PhD
All
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT03393741
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Inclusion Criteria:

• Men and women with histologically or cytologically demonstrated breast cancer that is deemed metastatic or incurable by the treating physician.
• It is medically appropriate to treat the patient with an antimitotic agent or an intravenous control chemotherapeutic agent by IV infusion at standard doses as per the treating physician. Please see NCCN guidelines for standard of care, p58 for standard chemotherapy regimens for recurrent or metastatic breast cancer7.
• The patient has measureable disease as determined by RECIST 1.1.
• Archived tissue is available from either primary, metastatic site or both.
• It is safe and feasible to obtain a research tumor biopsy on cycle 1 day 2 with a biopsy of an accessible lesion such as liver, lung, lymph node, skin, breast, or bone.
• All pre-chemotherapy test results (tests per treating oncologist discretion) have been reviewed and deemed appropriate for planned chemotherapy by the patient's treating oncologist.
Exclusion Criteria:

• HER2+ breast cancer by standard criteria.
• Pregnant women are excluded from this study because systemic chemotherapy may cause deleterious effects to the fetus. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with systemic chemotherapy, breastfeeding should be discontinued if the mother is enrolled in the trial.
• Planned treatment with hormonal therapy, or targeted oral therapy during trial enrollment.
Breast Cancer, Breast Neoplasms, Breast
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Neoadjuvant Weekly Paclitaxel and Biomarkers of Therapy Response

The hypothesis of this study is that paclitaxel levels increase chromosomal instability (CIN) in tumors and this is lethal to tumors that have pre-existing CIN. Treatment will be administered on an outpatient basis. Paclitaxel will be initiated as standard infusions on days 1, 8, and 15 of a 21-day cycle. Participants will continue with paclitaxel for cycles 2-4 prior to surgery.
Mark Burkard, MD, PhD
Female
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT03096418
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Inclusion Criteria:

• Women with pathologically demonstrated breast cancer
• Patients must be candidates for neoadjuvant paclitaxel chemotherapy by their treating oncologist. No other investigational or commercial therapeutic agents may be given concurrently with the paclitaxel.
• Patients must not have metastatic disease on staging work-up with CBC and liver function studies.
• A formalin-fixed paraffin embedded tumor block (preferred) or unstained slides must be available from a prior biopsy of the primary tumor or lymph node. A minimum of 8 slides must be available.
• The primary tumor or lymph node must be readily biopsied by surgery or radiology teams.
• The primary tumor must be measurable by an imaging modality prior to treatment. This imaging modality is to be repeated after completion of 4 cycles of paclitaxel and prior to surgery. Such imaging modalities may include ultrasound, CT, mammography, or MRI. MRI will be the preferred imaging modality if available because it has the highest accuracy and positive predictive value for predicting pathologic complete response.All imaging will be performed per standard of care at the discretion of the treating physicians.
• Subjects may not have had prior systemic chemotherapy regimens administered for treatment of their current breast cancer. However, studies (window studies, for example) that are deemed non-therapeutic, including those that utilize agents that are not FDA approved for the treatment of the patient's current breast cancer, are permitted.
• Patients must have adequate organ and marrow function as determined by the treating oncologist.
• Patient must be willing to undergo additional biopsy of breast tumor or lymph node.
• Patient must have the ability and willingness to sign a written informed consent document.
• Women of childbearing potential (per UWCCC policy definition) must agree to use effective contraception as discussed with treating oncologist for the duration of the study.
Exclusion Criteria:

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to paclitaxel including to other drugs formulated in Cremophor(R) EL (polyoxyethylated castor oil).
• Patients with known HIV due to concern that chemotherapy may cause further immunosuppression and potential infectious complications.
• Patients on non-aspirin anti-coagulation (Coumadin, heparins, or clopidogrel) or with documented bleeding disorders will be excluded due to risk of bleeding with biopsy.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active severe infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, other malignancies requiring therapy or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because paclitaxel is a pregnancy category D drug and may cause deleterious effects to the fetus. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with paclitaxel, breastfeeding should be discontinued if the mother is enrolled in the trial.
Breast, Breast Neoplasm Female
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Alpha/Beta CD19+ Depleted Haploidentical Transplantation + Zometa for Pediatric Hematologic Malignancies and Solid Tumors

This phase I trial studies the safety of transplantation with a haploidentical donor peripheral blood stem cell graft depleted of TCRαβ+ cells and CD19+ cells in conjunction with the immunomodulating drug, Zoledronate, given in the post-transplant period to treat pediatric patients with relapsed or refractory hematologic malignancies or high risk solid tumors.
Mario Otto, MD, PhD
All
7 Months to 21 Years old
Phase 1
This study is NOT accepting healthy volunteers
NCT02508038
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Inclusion Criteria:

• Availability of an eligible haploidentical donor
• Hematologic malignancy or solid tumor
• Patients with more than one malignancy (hematologic or solid tumor) are eligible
• Patients with hematologic malignancy must have no HLA identical sibling or suitable unrelated donor OR time needed to find an acceptable unrelated donor match would likely result in disease progression such that the patient may become ineligible for any type of potentially curative transplant
• Relapsed or primary therapy-refractory AML with bone marrow blast < 20%
• High-risk refractory or relapsed ALL in patients for whom transplantation is deemed indicated (relapse occurring < 30 months from diagnosis, patients relapsing after previous allogeneic transplant, relapse after 2nd remission, primary induction failure or hypodiploidy)
• Relapsed Hodgkin lymphoma unable to achieve 2nd remission or Very Good Partial Response (VGPR) and therefore ineligible to receive autologous hematopoietic stem cell transplant (auto-HSCT)
• Hodgkin lymphoma relapsing after auto-HSCT
• Primary refractory or relapsed non-Hodgkin lymphoma unable to achieve 2nd remission or VGPR and therefore ineligible to receive auto-HSCT
• Non-Hodgkin lymphoma relapsing after auto-HSCT
• Myelodysplastic Syndrome/Myeloproliferative Syndrome Solid Tumor
• Patients with solid tumor must have failed or have been ineligible to receive auto-HSCT or if auto-HSCT would not offer > 20% chance of cure
• Neuroblastoma
• high risk with relapsed or refractory disease
• Soft tissue sarcomas (Rhabdomyosarcoma, Ewing sarcoma, Primitive Neuroectodermal Tumor or other high-risk extracranial solid tumors)
• Relapsed or primary refractory metastatic
• 1st complete remission, but very high-risk features (i.e., < 20% survival with conventional therapy)
• Osteosarcoma
• Failure to achieve Complete Response (CR) following initial therapy
• Relapsed with pulmonary or bone metastases and did not achieve a CR with surgery and/or chemotherapy
• Karnofsky (patients > 16 years) or Lansky (patients 16 years or older) performance score of ≥ 60
• Life expectancy of ≥ 3 months
• Patient must have fully recovered from acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
• Study enrollment no earlier than 3 months after preceding HSCT
• Glomerular Filtration Rate (GFR) ≥ 60 ml/min/1.73m2
• Total bilirubin < 3 mg/dL
• ALT (alanine aminotransferase, SCPT) ≤ 5 x Upper LImit of Normal (ULN) for age
• Ejection fraction of > 40% by Multigated Acquisition Scan (MUGA) or echocardiogram
• No evidence of dyspnea at rest
• No supplemental oxygen requirement
• If measured, carbon monoxide diffusion capacity (DLCO) >50%
• No severe peripheral neuropathy, signs of leukoencephalopathy or active Central Nervous System (CNS) infection
• Patients with seizure disorders may be enrolled if seizures are well controlled on anticonvulsant therapy
• If of reproductive potential, negative pregnancy test and willing to use effective birth control method
• Informed consent from patient or legal guardian (if patient is minor) Inclusion Criteria for Donors:
• Donor must be 18 years of age minimum, 65 years of age maximum
• Donor must be in good general health as determined by evaluating medical provider
• Must meet donor criteria for human cells, tissues, and cellular and tissue-based products per Code of Federal Regulations 21 CFR 1271, subpart C. Specifically:
• Donor screening in accordance with 1271.75 indicates that the donor:
• Is free from risk factors for, and clinical evidence of, infection due to relevant communicable disease agents and diseases; and
• Is free from communicable disease risks associated with xenotransplantation; and
• The results of donor testing for relevant communicable disease agents in accordance with 1271.80 and 1271.85 are negative or nonreactive, except as provided in 1271.80(d)(1).
• Haploidentical by HLA-typing
• Preference will be given to donors who demonstrate KIR incompatibility with recipient HLA class I ligands defined as the donor expressing a KIR gene for which the corresponding HLA class I ligand is not expressed by the recipient.
• Negative testing for relevant communicable diseases:
• Hepatitis B surface antigen (HBsAg)
• Hepatitis B core antibody (Anti-HBc)
• Hepatitis C antibody (Anti-HCV)
• HIV 1 & 2 antibody (Anti-HIV-1, 2 plus O)
• HTLV I/II antibody (Anti-HTLV I/II)
• RPR (Syphilis TP)
• CMV (Capture CMV)
• MPX for: HepB (HBV-PCR), HepC (HCV-PCR), HIV (HIV-PCR)
• NAT for West Nile Virus (WNV-PCR)
• T. Cruzi
•EIA (Chagas)
Exclusion Criteria:

• Pregnant or breast-feeding
• HIV infection
• Heart failure or uncontrolled cardiac rhythm disturbance
• Uncontrolled, Serious Active Infection
• Prior organ allograft
• Significant serious intercurrent illness unrelated to cancer or its treatment not covered by other exclusion criteria expected to significantly increase the risk of HSCT
• Any mental or physical condition, in the opinion of the PI (or PI designee), which could interfere with the ability of the subject (or the only parent or legal guardian available to care for the subject) to understand or adhere to the requirements of the study
• Enrollment in any other clinical study from screening up to Day 100 (unless PI judges such enrollment would not interfere with endpoints of this study) Exclusion Criteria for Donors:
• Lactating females
• Pregnant females
Bones and Joints, Brain and Nervous System, Colon, Esophagus, Eye and Orbit, Hodgkin's Lymphoma, Ill-Defined Sites, Kidney, Leukemia, other, Liver, Lung, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Non-Hodgkin's Lymphoma, Other Female Genital, Other Hematopoietic, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Soft Tissue, Stomach, Urinary Bladder, Brain/Central Nervous System, Hematologic cancers, other, Leukemia, Lymphoma, Sarcoma, Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Myelodysplastic Syndrome, Myeloproliferative Syndrome, Rhabdomyosarcoma, Ewing Sarcoma, Primitive Neuroectodermal Tumor, Osteosarcoma, Neuroblastoma
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Epidural Anesthesia Within an Enhanced Recovery Pathway in Reducing Pain in Patients Undergoing Gynecologic Surgery

This randomized clinical trial studies epidural anesthesia within an enhanced recovery pathway (ERP) in reducing pain in patients undergoing gynecologic surgery. An epidural analgesia (pain relief) is a small tube placed in the lower back that numbs the nerves and stops the feeling of pain. It stays in place for several days after surgery and may be helpful for pain control in patients with gynecologic cancer after surgery. ERP is a set of specific steps used before, during, and after surgery by health care providers to care for patients after surgery. ERPs include patient education, not using laxatives before surgery, increasing activity after surgery, and scheduled use of medications for pain and nausea. Giving epidural anesthesia as part of an ERP may improve pain control in patients undergoing gynecologic surgery.
Lisa Barroilhet, MD
Female
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT02423876
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Inclusion Criteria:

• Patients undergoing gynecologic surgery via midline vertical laparotomy at University of Wisconsin Hospital and Clinics (UWHC)
• Patients must be English speaking
• Patients must have the ability to understand visual and verbal pain scales
• Patients must be eligible for epidural placement
Exclusion Criteria:

• Known allergy to local anesthetics
• Known history of chronic pain disorders and/or chronic opioid use defined as > 10 mg of oral (PO) morphine or equivalent used daily for at least 30 days prior to enrollment
• Patient is a prisoner or incarcerated
• Significant liver disease that would inhibit prescription of opioids
• Significant kidney disease that would inhibit administration of gabapentin
• Patient has a history of opioid dependence requiring rehabilitation or the use of opioid antagonists
• Patient is pregnant
• Patients with a planned exploration with biopsies (no organs removed) will be excluded from the study
Intraoperative Complication, Malignant Female Reproductive System Neoplasm, Pain, Cervix, Corpus Uteri, No Disease, Other Female Genital, Ovary, Uterus
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Gedatolisib Plus Talazoparib in Advanced Triple Negative or BRCA1/2 Positive, HER2 Negative Breast Cancers

This study is designed to determine the RP2D of gedatolisib in combination with talazoparib and to evaluate the efficacy of this combination in advanced HER2 negative breast cancer that is triple negative or BRCA1/2 positive (deficient).
Kari Wisinski, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT03911973
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Inclusion Criteria:

• Male or female ≥ 18 years of age at time of consent.
• Subjects with histologically confirmed breast cancer that is advanced (defined as metastatic or unresectable).
• Phase II Cohort A: Patients with advanced triple negative breast cancer (TNBC) with negative or unknown germline BRCA status. Variants of undetermined significance in BRCA 1/2 should be considered negative.
• Note: most recent tumor biopsy must be ER/PR negative or have ER and PR <10% and all prior biopsies of metastatic sites cannot have ever had ER or PR ≥20%.
• Note: HER2 is considered negative if ISH negative by ASCO/CAP guidelines or HER2+ 0 or 1+ on IHC or 2+ with negative ISH
• Phase II Cohort B: Patients with advanced HER2 negative breast cancer and a germline BRCA1 or 2 (1/2) mutation ---Note: HER2 is considered negative if ISH negative by ASCO/CAP guidelines or HER2+ 0 or 1+ on IHC or 2+ with negative ISH
• Phase I run-in: meets criteria for either cohort A or B
• Phase I run-in: Measurable or evaluable (non-measurable) disease (see section 9.2 for more detail).
• Phase II: Measurable disease by RECIST 1.1 is required.
• Prior therapy:
• Cohort A: At least one line of prior systemic therapy for advanced breast cancer (chemotherapy or other targeted therapy allowed). No more than 3 lines of prior chemotherapy for advanced disease are allowed. No limit on prior endocrine or targeted therapies.
• Cohort B: No more than 2 lines of prior chemotherapy for advanced disease are allowed. No limit on prior endocrine or targeted therapies.
• Both cohorts: no prior PARP inhibitor for advanced breast cancer
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 within 28 days prior to study registration.
• Life expectancy of 12 weeks or greater as determined by the treating physician.
• Demonstrate adequate organ function as defined in the table in the protocol; all screening labs to be obtained within 28 days prior to registration.
• Archived tumor tissue available (Metastatic disease from non-bone and non-brain sites preferred, but primary breast or lymph node tissue is permitted. Confirmation of available tissue only- tumor samples do not need to be shipped for eligibility purposes. Tumor samples do not need to be shipped until subject is confirmed eligible and is registered for treatment.
• Ability to take oral medications.
• No history of type I diabetes. For patients with known type II diabetes, must have controlled diabetes (Hgb A1c < 7.0 mmol/L within 30 days of study entry) with no more than one oral anti-diabetic agent and no insulin.
• No active central nervous system (CNS) metastatic disease. NOTE: Subjects with CNS involvement must meet ALL of the following to be eligible:
• At least 28 days from prior definitive treatment of their CNS disease by surgical resection, SBRT or WBRT at the time of registration
• Asymptomatic and off systemic corticosteroids and/or enzyme-inducing antiepileptic medications for brain metastases for >14 days prior to registration.
• Provided written informed consent and HIPAA authorization for release of personal health information, approved by an Institutional Review Board (IRB).
• NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Women of childbearing potential (WOCP) must not be pregnant or breast-feeding. A negative serum or urine pregnancy test is required within 14 days of study registration. If the urine test cannot be confirmed as negative, a serum pregnancy test will be required.
• Women of childbearing potential (WOCP) must be willing to use two effective methods of birth control such as an oral, implantable, injectable, or transdermal hormonal contraceptive, an intrauterine device (IUD), use of a double barrier method (condoms, sponge, diaphragm, or vaginal ring with spermicidal jellies or cream), vasectomized partner, or total abstinence for the course of the study until 7 months after the last dose of study drug.
• NOTE; Women are considered to be of childbearing potential unless they are postmenopausal (≥45 years of age and has not had menses for greater than 12 consecutive months) or bilateral oophorectomy or surgically sterile (bilateral tubal ligation or hysterectomy) or not heterosexually active for the duration of the study and willing to continue for at least 7 months after the last dose of study drug.
• Men who are not surgically sterile (vasectomy) must agree to use an acceptable method of contraception. Male subjects with female sexual partners who are pregnant, possibly pregnant, or who could become pregnant during the study must agree to use condoms from the first dose of study drug through at least 4 months after the last dose of study drug. Total abstinence for the same time period is an acceptable alternative.
• 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. Patients with a known history of HIV must have a CD4 count ≥ the institutional lower limit of normal within 28 days prior to registration. Patients with HIV must also be on a stable anti-retroviral regimen for ≥ 28 days before registration.
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
• Patients who have had chemotherapy, targeted therapy, or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from acute effects of any prior therapy to baseline or Grade ≤1. Grade 2 or higher exceptions include alopecia, up to grade 2 neuropathy or other Grade 2 AEs or lab values not constituting a safety risk in the opinion of the treating physician.
• 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 prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of this investigational regimen.
• Known hypersensitivity to any of the excipients of gedatolisib or talazoparib.
• Any impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of talazoparib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
• Known active hepatitis B or C (testing not mandatory). Patients who have completed curative therapy for HCV are eligible.
• Known history of myelodysplastic syndrome or acute myeloid leukemia.
• Subjects with any of the following conditions:
• History of drug-induced pneumonitis within last 12 months or any history of pneumonitis related to an mTOR inhibitor or current clinically significant pulmonary disease not due to the breast cancer.
• 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.
• Subject is currently receiving warfarin or other coumarin-derived anticoagulant for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), direct thrombin inhibitors (such as dabigatran) or novel oral anticoagulants (such as rivaroxaban or apixaban) are allowed as long as the patient has been on this therapy for at least 14 days with no clinically significant bleeding.
Breast, TNBC - Triple-Negative Breast Cancer
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Retinoid 9cUAB30 in Producing a Biologic Effect in Patients With Early Stage Breast Cancer

This phase 1b trial studies the biologic effect of 9cUAB30 on early stage breast cancer. 9cUAB30 is a retinoid X receptor (RXR)-selective retinoid that acts in a tissue selective manner with the goal of minimizing side effects, a necessary feature of agents under development for cancer prevention.
Lee Wilke, MD
Female
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT02876640
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Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status =< 1 or Karnofsky >= 70%
• Invasive breast cancer diagnosed by needle core biopsy between 0.5 cm and 5 cm in size based on imaging, that is estrogen receptor positive (ER+) or estrogen receptor negative (ER-), Her2neu positive or negative OR ductal carcinoma in situ (DCIS) of the breast diagnosed by core needle biopsy and at least 1.0 cm in size based on imaging. Grade 3 ER+ DCIS will be allowed as well as ER- DCIS of any grade. For DCIS-only lesions, the imaging abnormality corresponding to the cancer must be at least 1.0 cm in size (i.e. calcifications, distortion or mass on mammogram, or mass or non-mass enhancement on magnetic resonance imaging [MRI])
• White blood cells (WBC) >= 3000/mm^3
• Platelets >= 100,000/mm^3
• Hemoglobin > 10 g/dL
• Bilirubin =< upper limit of institutional normal
• Aspartate aminotransferase (AST) =< upper limit of institutional normal
• Creatinine within institutional normal limits
• Triglycerides =< 1.5 x upper limit of normal (ULN)
• Cholesterol =< 1.5 x ULN
• Participants must agree to discontinue all supplements containing vitamin A while taking study medication and for thirty days after the last dose of study medication.
• Have not been treated with chemotherapy, or biological therapy in the last 5 years. We do not know if the previous treatment will have an effect on the tissues to be examined.
• Have not used tamoxifen, raloxifene, or other antiestrogen compounds within 6 months of study entry. If used within 5 years of study entry, total duration of use must be less than 6 months
• Have not used exogenous hormone replacement therapy or hormonal contraception in the year prior to diagnosis. The use of non-systemic estrogen (such as vaginal estrogen use) is allowed
• The effects of 9cUAB30 on the developing human fetus are unknown. Since retinoids are known to be teratogenic, to avoid any complications due to unintentional pregnancies only postmenopausal women and some premenopausal women (as outlined below) will be eligible; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
• Women will be considered postmenopausal if one of the following is met:
• Prior bilateral oophorectomy
• 60 years of age or older
• Age less than 60 years; amenorrheic for 12 or more months; and follicle stimulating hormone (FSH) in the postmenopausal range
• Premenopausal women without childbearing potential are eligible to participate if one of the following criteria is met:
• Prior hysterectomy
• Prior fallopian tubal ligation (cut, tied, or sealed)
• Prior placement of permanent intratubal contraceptive devices (e.g. Essure)
• Partner with prior vasectomy and willing to use barrier method (e.g. condoms)
• Participants must have the ability to understand, and the willingness to sign, a written informed consent document
Exclusion Criteria:

• Participant taking medications that might interact with 9cUAB30
• Participant who has started or increased dosage of lipid-lowering agents in the last 30 days of enrollment
• Participant receiving any other investigational agents within 30-days of enrollment nor during study participation with the exception of 18F-FFNP investigational imaging agent
• Participant with a history of allergic reactions attributed to compounds of similar chemical or biologic composition of retinoids
• Participant with an uncontrolled intercurrent illness including, but not limited to;
• Ongoing or active infection,
• Symptomatic congestive heart failure,
• Unstable angina pectoris,
• Cardiac arrhythmia,
• A persistent grade 3 hypertension
• For grade 1, grade 2, and non-persistent grade 3 hypertension, repeat blood pressure reading after 5 minutes. If the average reading of the two measurements is grade 3 (systolic BP >=160 mm Hg or diastolic BP >=100 mm Hg) the patient is not eligible. If the average reading of the two measurements is less than or equal to grade 2, then the participant is eligible. If the average of the 2 readings is grade 1 or grade 2 hypertension, document the appropriate level hypertension on the baseline symptom form.
• Psychiatric illness/social situations that will limit compliance with study requirements
• Participant who is breastfeeding or planning to breastfeed for a month post last dose of study agent
• Participant known to be human immunodeficiency virus (HIV)-positive, as we do not know the effects of study drug on suppression of the immune system.
• Participant with a history of a second cancer diagnosis or reoccurrence < 5 years from study entry with the exception of a history of squamous or basal cell carcinoma of the skin < 5 years from study entry will not be excluded from this study. This is to eliminate the residual effects of any previous treatments for those cancers.
• Participant with history of ipsilateral breast radiation
• Participant's core biopsy slides suggest that later re-sectioning will not contain sufficient tumor to allow for an adequate evaluation of Ki67 and TUNEL assays, at a minimum
Breast, Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage IA Breast Cancer AJCC v8, Anatomic Stage IB Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIA Breast Cancer AJCC v8, Anatomic Stage IIB Breast Cancer AJCC v8, Breast Ductal Carcinoma In Situ, Early-Stage Breast Carcinoma, Invasive Breast Carcinoma, Prognostic Stage I Breast Cancer AJCC v8, Prognostic Stage IA Breast Cancer AJCC v8, Prognostic Stage IB Breast Cancer AJCC v8, Prognostic Stage II Breast Cancer AJCC v8, Prognostic Stage IIA Breast Cancer AJCC v8, Prognostic Stage IIB Breast Cancer AJCC v8
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Ribociclib and Bicalutamide in AR+ TNBC

This is an open label, multi-institutional, single arm phase II trial of ribociclib in combination with bicalutamide in advanced AR+ triple-negative breast cancer. No randomization or blinding is involved.
Kari Wisinski, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT03090165
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Androgen Receptor (AR) positivity definitions -Phase I: Metastatic or unresectable AR+ triple-negative breast cancer (TNBC); AR positivity defined as IHC staining of >0% of tumor nuclei. OR -Phase II: Metastatic or unresectable AR+ triple-negative breast cancer (TNBC); AR positivity defined as IHC staining of ≥10% of tumor nuclei. Inclusion Criteria for Phase I and II study. In addition to being AR positive as defined in protocol, subjects must also meet all of the following applicable inclusion criteria.
• Histological or cytological confirmed, metastatic or unresectable triple-negative breast cancer (TNBC). TNBC will be defined as expression of ER<10%, PR< 10% and HER2 negative either by IHC (0, 1+ are negative, 2+ equivocal) or in situ hybridization method (ratio <2.0 is negative).
• 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.
• Up to 1 prior line of systemic therapy for metastatic disease is allowed. Combination therapy will be considered 1 line.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0 or 1 within 28 days prior to registration.
• Life expectancy of > 12 weeks as determined by the treating physician.
• Measurable disease according to RECIST 1.1 within 28 days prior to registration.
• No active central nervous system (CNS) metastatic disease. NOTE: Subjects with CNS involvement must meet ALL of the following to be eligible:
• At least 28 days from prior definitive treatment of their CNS disease by surgical resection, stereotactic body radiation therapy (SBRT) or whole brain radiation treatment (WBRT) at the time of registration
• AND asymptomatic and off systemic corticosteroids and/or enzyme-inducing anti-epileptic medications for brain metastases for >14 days prior to registration.
• Prior cancer treatment must be completed at least 14 days prior to registration and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to ≤grade 1 or to baseline prior to initiation of that therapy.
• Screening rate-corrected QT interval (QTc) must be <450msec and a resting heart rate of at least 50-90 bpm via a standard 12-lead ECG within 28 days prior to registration.
• Demonstrate adequate bone marrow and organ function as defined in the protocol; all screening labs to be obtained within 28 days prior to registration.
• Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), or they are naturally postmenopausal for at least 12 consecutive months, or her male partner has had a vasectomy at least 6 months prior to screening (The sterilized male partner must be her only sexual partner.).
• Females of childbearing potential and males must be willing to abstain from heterosexual activity or must agree to use adequate contraception (hormonal or barrier method) for the duration of study participation and for 3 weeks after discontinuation of study treatment.
• 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.
• Able to swallow bicalutamide and ribociclib capsules/tablets.
Exclusion Criteria:

• Prior therapy with AR antagonists including but not limited to bicalutamide, enzalutamide, abiraterone and orteronel.
• Prior therapy with any CDK 4/6 inhibitors with the exception of participation in a window or preoperative study for Stage I-III operable breast cancer..
• Active infection requiring systemic therapy.
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
• Known additional malignancy that is active and/or progressive requiring treatment; 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 three years.
• Treatment with any investigational drug within 14 days prior to registration or within 5 half-lives of the investigational product, whichever is longer. Immunotherapies such as PD-L1 or PD-1 inhibitors only require a 14 day window, regardless of half-life.
• Subject who has received radiotherapy <14 days prior to registration, and who has not recovered to grade 1 or better from related side effects of such therapy (exceptions include alopecia and any adverse events deemed by the investigator to be unlikely to interfere with the study drug safety).
• 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).
• Known hypersensitivity to any of the excipients of ribociclib or bicalutamide.
• Any impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
• Known history of HIV infection (testing not mandatory).
• 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 (e.g. chronic pancreatitis, chronic active hepatitis, active untreated or uncontrolled fungal, bacterial or viral infections, etc.).
• Subjects with any of the following conditions are excluded:
• Serious or non-healing wound, ulcer, or bone fracture.
• 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.
• Any history of arterial or venous thrombosis/thromboembolic event, including pulmonary embolism within the past 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 arrhythmias (e.g. ventricular tachycardia) or clinically significant, complete left bundle branch block, high-grade AV block (e.g. bifascicular block, Mobitz type II and third-degree AV block).
• Any episode of atrial fibrillation in the prior 12 months.
• Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome.
• Concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued (within 5 half-lives or 7 days prior to starting study drug) or replaced by safe alternative medication. See ManualDocuments/Info tab of the EDC for list of medications.
• Systolic blood pressure (SBP) >160 mmHg or <90 mmHg at screening.
• Currently receiving any known strong inducers or inhibitors of CYP3A4/5 which cannot be discontinued 7 days prior to starting study drug (see Appendix 1 for details).
• Subject is currently receiving or has received systemic corticosteroids <14 days prior to starting study drugs. The following uses of corticosteroids are permitted: a short duration (<5 days) of systemic corticosteroidssingle doses, any duration of topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular).
• Subject is currently receiving warfarin or other coumarin-derived anticoagulant for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), novel oral anticoagulants (NOACs) or fondaparinux is allowed.
• In subjects with a diagnosis of cirrhosis, sSubjects with a Child-Pugh score B or C are excluded. Please see chart in the ManualDocuments/Info tab of the electronic data capture system (EDC) for Child-Pugh score calculation. If subject does not have diagnosed or suspected cirrhosis, the Child-Pugh score does not need to be calculated.
• Subjects taking herbal supplements (St. John's Wort, gingko balboa, etc.) must discontinue these supplements 14 days prior to study registration.
• Consumption of grapefruit, grapefruit hybrids, pummelos, star-fruit, Seville oranges or products containing the juice of each within 7 days prior to study registration.
Breast, Triple Negative Breast Cancer
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Dose Escalation Study of CLR 131 in Children, Adolescents, and Young Adults With Relapsed or Refractory Malignant Tumors Including But Not Limited to Neuroblastoma, Rhabdomyosarcoma, Ewings Sarcoma, and Osteosarcoma (CLOVER-2)

The study evaluates CLR 131 in children, adolescents, and young adults with relapsed or refractory malignant solid tumors and lymphoma and recurrent or refractory malignant brain tumors for which there are no standard treatment options with curative potential.
Diane Puccetti, M.D.
All
2 Years to 25 Years old
Phase 1
This study is NOT accepting healthy volunteers
NCT03478462
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Inclusion Criteria:
All Patients
• Previously confirmed (histologically or cytologically) pediatric solid tumor (e.g., neuroblastoma, sarcoma), lymphoma (including Hodgkin's lymphoma), or malignant brain tumors that are clinically or radiographically suspected to be relapsed, refractory, or recurrent for which there are no standard treatment options with curative potential. Note: patients with diffuse intrinsic pontine glioma (DIPG) may enroll without histological or cytological confirmation.
• ≥ 2 years of age and ≤ 25 years of age at time of consent/assent
• If ≥ age 16 years, Karnofsky performance status of ≥ 60. If < age 16 years, Lansky performance status ≥ 60
• Platelets ≥ 75,000/µL (last transfusion, if any, must be at least 1 week prior to study registration, and, unless deemed medically necessary, no transfusions are allowed between registration and dosing)
• Absolute neutrophil count ≥ 750/µL
• Hemoglobin ≥ 8 g/dL (last transfusion must be at least 1 week prior to study registration, and, unless deemed medically necessary, no transfusions are allowed between registration and dosing)
• Using the bedside Schwartz formula, estimated GFR (creatinine clearance) > 60 ml/min/1.73m2
• Alanine aminotransferase < 3 × ULN
• Bilirubin < 2 × ULN
• Patients who have undergone autologous or allogeneic bone marrow transplant must be at least 3 months from transplant.
• Patients enrolling at total dose levels > 30 millicurie (mCi)/m2 must have availability or ability to collect an autologous hematopoietic stem cell back-up product prior to CLR 131 administration. At minimum, 2 x 10^6/kg cryopreserved CD34+ cells must be available.
• Patient or his or her legal representative is judged by the Investigator to have the initiative and means to be compliant with the protocol. Patients with Pediatric Solid Tumor or Lymphoma
• At least 1 measurable lesion with longest diameter of at least 10 mm. Patients with a lesion(s) that are determined to be Metaiodobenzylguanidine (MIBG) or positron emission tomography (PET) positive may be enrolled at the investigator's discretion, even if not associated with a measurable lesion of at least 10 mm. Patients with neuroblastoma who have detectable disease may enroll provided they meet the requirements of the International Neuroblastoma Response Criteria.
• Patients with known brain metastases must have completed any radiotherapy or systemic treatments for brain metastases prior to enrollment; by investigator assessment be considered stable with no new signs or symptoms for at least 1 month, and on a stable dose of steroids (unchanged for three weeks prior to registration or on a steroid tapering regimen). Patients with Recurrent or Refractory Brain Tumors
• At least 1 measurable lesion with longest diameter of at least 10 mm on any imaging sequence.
• Patients with previously known neurological deficits must be clinically stable at time of enrollment and able to complete all study related procedures. Patients with documented or newly diagnosed neurological deficits will be enrolled at the investigator's discretion.
• If patient receives steroids for neurological symptom control, the dose must be stable (unchanged for three weeks prior to registration) or on a steroid tapering regimen. Initiation of steroids per routine care immediately prior to CLR 131 dosing is acceptable.
Exclusion Criteria:

• Patients receiving active treatment for central nervous system metastases or those that are likely to require active treatment during anticipated participation in this trial. Patients with stable brain metastases treated with steroids may enroll at the investigator's discretion
• For solid tumor and lymphoma patients only, central nervous system involvement unless previously treated with surgery, systemic therapy, or radiotherapy with the patient neurologically stable. Patients with metastatic brain tumors that have been previously treated are allowed, provided the patient is neurologically stable (determined at the investigator's discretion).
• Antitumor therapy or investigational therapy, within 2 weeks of dosing. For certain types of radiation (craniospinal, total abdominal, whole lung [spot irradiation to skull-based metastases is not considered craniospinal radiation for the purposes of this study]), at least 3 months must have elapsed. No washout is required for palliative focal radiation. NOTE: Patients participating in non-interventional clinical trials (i.e., non-drug) are allowed to participate in this trial
• Patients previously treated with iodine-131 (131I)-MIBG who have already received a cumulative I-131 dose > 54 mCi/kg or who would exceed 54 mCi/kg by participating in this trial, are not eligible.
Anus, Bones and Joints, Brain and Nervous System, Breast, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Hodgkin's Lymphoma, Ill-Defined Sites, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung, Non-Hodgkin's Lymphoma, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Soft Tissue, Stomach, Thyroid, Urinary Bladder, Head and Neck, Gastrointestinal cancers, other, Colon and Rectum, Anal, Sarcoma, Melanoma/Skin cancer, Uterus, Genitourinary cancers, other, Bladder, Brain/Central Nervous System, Endocrine cancers, Lymphoma, Pediatric Solid Tumor, Pediatric Lymphoma, Pediatric Brain Tumor, DIPG, Neuroblastoma, Ewing Sarcoma, Rhabdomyosarcoma, Osteosarcoma
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Dose-Escalation/Expansion of RMC-4630 and Cobimetinib in Relapsed/Refractory Solid Tumors and RMC-4630 and Osimertinib in EGFR Positive Locally Advanced/Metastatic NSCLC

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of RMC-4630 and cobimetinib in adult participants with relapsed/refractory solid tumors with specific genomic aberrations and to identify the recommended Phase 2 dose (RP2D); and to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of RMC-4630 and osimertinib in adult participants with EGFR mutation-positive locally advanced or metastatic NSCLC.
Dustin Deming, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT03989115
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Inclusion Criteria:

• Age ≥18 years
• For RMC-4630 + Cobimetinib only
•Participants who have advanced solid tumors that have failed, are intolerant to, or are considered ineligible for standard of care anti-cancer treatments including approved drugs for oncogenic drivers in their tumor type.
• For RMC-4630 + Osimertinib only
•Locally advanced or metastatic EGFR mutant NSCLC not amenable to curative surgery or radiotherapy
• For RMC-4630 + Cobimetinib only
•Participants must have one of the following genotypic aberrations: KRAS mutations and amplifications, BRAF Class 3 mutations, or NF1 LOF mutations
• For RMC-4630 + Osimertinib only
•Evidence of radiological documentation of progression with osimertinib monotherapy or an osimertinib containing regimen. Participants should not be considered a current candidate for 1st generation EGFR TKI's by the investigator.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
• Adequate hematological, hepatic, and renal function
• Capable of giving signed informed consent form (ICF). Willing and able to compile with study requirements and restrictions
• Life expectancy >12 weeks
• Female of childbearing potential and males with partners of childbearing potential must comply with effective contraception criteria .
Exclusion Criteria:

• Primary central nervous system (CNS) tumors.
• Known or suspected leptomeningeal or brain metastases or spinal cord compression.
• For RMC-4630 + osimertinib arm only
•Known or suspected Small cell, squamous, or pleomorphic lung transformations
• Clinically significant cardiac disease
• Active, clinically significant interstitial lung disease or pneumonitis
• History or current evidence of retinal pigment epithelial detachment (RPED), central serous retinopathy, retinal vein occlusion (RVO), or predisposing factors to RPED or RVO
• Known HIV infection or active/chronic hepatitis B or C infection.
• Any other unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator, jeopardize the safety of a participant, impact their expected survival through the end of the study participation, and/or impact their ability to comply with the protocol prior/concomitant therapy
• Females who are pregnant or breastfeeding
Anus, Bones and Joints, Brain and Nervous System, Breast, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Hematopoietic, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Soft Tissue, Stomach, Thyroid, Urinary Bladder, Head and Neck, Gastrointestinal cancers, other, Colon and Rectum, Anal, Sarcoma, Melanoma/Skin cancer, Uterus, Genitourinary cancers, other, Bladder, Brain/Central Nervous System, Endocrine cancers, Hematologic cancers, other, Solid Tumor
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T-DM1 and Palbociclib for Metastatic HER2 Breast Cancer (T-DM1)

This is a randomized phase II study to evaluate if the combination of T-DM1 with palbociclib improves progression-free survival compared to single agent T-DM1in patients with metastatic HER2 positive breast cancer
Kari Wisinski, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT03530696
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Inclusion Criteria:
1. Be informed of the investigational nature of the study and all pertinent aspects of the trial 2. Sign and provide written consent in accordance with institutional and federal guidelines. 3. ECOG Performance status of 0-2 4. Recurrent or metastatic HER2-positive breast cancer (HER2 positive is defined per ASCO-CAP guidelines) 5. Adequate cardiac reserve (EF≥50%) 6. Serum creatinine ≤ 1.5 x institutional upper limit of normal (IULN), bilirubin ≤ 2.0, and an SGOT/SGPT/alkaline phosphatase ≤ 2.0 x IULN 7. Adequate bone marrow function (ANC ≥1000, Platelets ≥100,000/ml, Hemoglobin ≥10gm/dL) 8. Be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other trial procedures 9. Been treated with pertuzumab previously (neoadjuvant or metastatic setting). Patients who weren't able to tolerate pertuzumab due to side effects can be eligible for study upon discussion with the study PI 10. No more than 2 lines of therapy in the metastatic disease setting
Exclusion Criteria:
1. HER2 negative tumors 2. Prior treatment with T-DM1 3. Prior treatment with CDK 4/6 inhibitors 4. Known active CNS metastases or carcinomatous meningitis. Patients with stable CNS metastases including brain metastases who have completed a course of radiotherapy are eligible for the study provided they are clinically stable. However, oral corticosteroids for control of CNS symptoms are not allowed on study 5. Known documented or suspected hypersensitivity to the components of the study drug(s) or analogs. 6. Uncontrolled systemic illness, including but not limited to ongoing or active infection 7. Symptomatic congestive heart failure, unstable angina pectoris, stroke or myocardial infarction within 3 months 8. Be pregnant or breast feeding. Female subjects must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy. All female subjects with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrollment and must agree to use effective contraception during the period of therapy 9. Concurrent hormonal or other anti-neoplastic therapy is not allowed. Patients can receive supportive therapy like bone-directed therapy including bisphosphonates or denosumab
HER2-positive Breast Cancer, Breast Cancer, Breast Cancer Stage, Recurrent Breast Cancer, Metastatic Breast Cancer, HER2 Positive Breast Carcinoma, Breast
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APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors (SPARTA)

The primary Phase 1 purpose of this study is to assess overall safety and tolerability and recommended Phase 2 dose (RP2D) of APL-101. The Phase 2 portion will assess efficacy of the dose determined in Phase 1 in individuals with Non-Small Cell Lung Cancer with c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors
Mark Burkard, MD, PhD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT03175224
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Major
Inclusion Criteria:

• Able to understand and comply with study procedures, understand the risks involved, and provide written informed consent.
• For Phase 1, histologically and / or cytological confirmed unresectable or metastatic solid malignancy, refractory to standard therapies with no more than three prior lines of therapy.
• For Phase 2, five cohorts will be enrolled: Cohort A-1: NSCLC EXON 14 skip mutation (c-Met naïve) for first line treatment, Cohort A-2: NSCLC EXON 14 skip mutation (c-Met naïve) pretreated subjects with no more than 3 lines of prior therapy, Cohort B: NSCLC EXON 14 skip mutation (c-Met experienced; radiographic progression on prior c-Met inhibitor), Cohort C: basket of tumor types with c-Met high level amplification (NSCLC EXON 14 skip mutation excluded), Cohort D: basket of tumor type with c-Met fusions.
• Local/archival result (tissue and/or plasma) of a positive c-Met dysregulation is required
• Measurable disease according to RECIST v1.1. (or relevant criteria per tumor type).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• For all prior anticancer treatment, including radiotherapy, chemotherapy or targeted agents or hormonal therapy, a duration of more than 30 days or 5 half-lives of the agents used, whichever is shorter, must have elapsed, and any encountered toxicity must have resolved to levels meeting all the other eligibility criteria prior to the first dose of study treatment.
• No planned major surgery within 4 weeks of first dose of APL-101 Major
Exclusion Criteria:

• Hypersensitivity to APL-101, excipients of the drug product, or other components of the study treatment regimen.
• Known mutation/gene rearrangement of EGFR (except for Cohort C), ALK, ROS1, RET, NTRK, KRAS, and BRAF.
• Unstable angina or myocardial infarction within 1 year prior to first dose of APL-101, symptomatic or unstable arrhythmia requiring medical therapy, history of congenital prolonged QT syndrome, prolonged QT interval corrected by Fridericia formula (QTcF) at screening (> 450 msec based on the average of 3 measurements), or concurrent treatment with a medication that is a known risk for prolonging the QT interval.
• Unable to swallow orally administered medication whole.
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter drug absorption (e.g., Crohn's, ulcerative colitis, active inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome).
• Women who are breastfeeding.
Solid Tumor, Advanced Cancer, Renal Cancer, Gastric Cancer, Gastroesophageal Junction Adenocarcinoma, NSCLC, Lung Cancer, Brain Tumor, Glioblastoma Multiforme, Anus, Bones and Joints, Brain and Nervous System, Breast, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Ill-Defined Sites, Kaposi's Sarcoma, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung, Melanoma, Skin, Mycosis Fungoides, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Soft Tissue, Stomach, Thyroid, Unknown Sites, Urinary Bladder, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Melanoma/Skin cancer, Sarcoma, Uterus
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Assessing the Clinical Benefit of Molecular Profiling in Patients With Solid Tumors

Many patients are treated for advanced cancer without knowledge of underlying molecular features that might indicate FDA approved therapies or potential eligibility for biomarker-selected clinical trials. The Strata Trial (STR-001-001) has been initiated by Strata Oncology to evaluate the clinical benefit of systematic comprehensive genomic profiling for participants with advanced cancer using real-world data and endpoints, while assessing the proportion of participants available for clinical trials and approved targeted therapies in advanced and/or aggressive cancers. The Strata Trial uses surplus, or leftover, tumor specimens for molecular profiling and does not require additional study-specific procedures.
Mark Burkard, MD, PhD
All
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT03061305
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Inclusion Criteria:

• Subjects must be ≥ 18 years of age.
• Subjects must have histologically documented solid tumors (including lymphoma and multiple myeloma).
• Specific criteria for individual tumor types are as follows: 1. Participants with gliomas are eligible at any stage of disease 2. Participants with pancreatic carcinoma are eligible at any stage of disease 3. Participants with rare tumors (i.e. cancer started in an unusual place in the body, it is unusual type and requires special treatment) are eligible at stages II-IV. 4. Participants with other tumor types must have recurrent, relapsed, refractory, metastatic, or advanced stages III or IV cancer.
• Must have an adequate formalin-fixed paraffin-embedded tumor specimen for genomic sequencing.
Anus, Any Site, Bones and Joints, Brain and Nervous System, Breast, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Hodgkin's Lymphoma, Ill-Defined Sites, Kaposi's Sarcoma, Kidney, Larynx, Leukemia, other, Lip, Oral Cavity and Pharynx, Liver, Lung, Lymphoid Leukemia, Melanoma, Skin, Mycosis Fungoides, Myeloid and Monocytic Leukemia, Non-Hodgkin's Lymphoma, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Hematopoietic, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Soft Tissue, Stomach, Thyroid, Unknown Sites, Urinary Bladder, Head and Neck, Gastrointestinal cancers, other, Colon and Rectum, Anal, Sarcoma, Melanoma/Skin cancer, Hematologic cancers, other, Uterus, Genitourinary cancers, other, Bladder, Brain/Central Nervous System, Endocrine cancers, Leukemia, Cancer, Adult Solid Tumor, Lymphoma, Multiple Myeloma
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Study to Evaluate the Efficacy and Safety of Ibrexafungerp in Patients With Fungal Diseases That Are Refractory to or Intolerant of Standard Antifungal Treatment (FURI)

This is a multicenter, open label, non-comparator, single arm study to evaluate the efficacy and safety of ibrexafungerp (SCY-078) in patients ≥ 18 years of age with a documented fungal disease that has been intolerant or refractory (rIFI) to Standard of Care (SoC) antifungal treatment.
David Andes, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT03059992
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Key
Inclusion Criteria:
1. Must have a documented eligible invasive and/or severe fungal disease that is refractory or intolerant to Standard-of-Care treatment 2. Be able to tolerate medication orally or through a nasogastric (NG) tube or percutaneous endoscopic gastrostomy (PEG) tube 3. Be able to understand and sign a written informed consent form (ICF), which must be obtained prior to treatment and any study-related procedures. 4. Be able to understand and sign a consent or authorization form which shall permit the use, disclosure and transfer of the subject's personal health information. (e.g., in the U.S. HIPAA Authorization form). 5. Be able to understand and follow all study-related procedures including study drug administration. 6. Agree to use a medically acceptable method of contraception while receiving protocol-assigned product. Key
Exclusion Criteria:
1. An invasive fungal disease with CNS involvement. 2. Subject has an inappropriately controlled fungal disease source (e.g., persistent catheters that cannot be removed and are likely the source of infection). 3. Subject is hemodynamically unstable, requiring vasopressor medication for blood pressure support. 4. A life expectancy < 30 days. 5. Subject with abnormal liver test parameters: aspartate aminotransferase (AST), alanine aminotransferase (ALT) >10 x the upper limit of normal (ULN), and/or total bilirubin > 5 x ULN. 6. Subject is pregnant or lactating. 7. Subject has used an investigational drug within 30 days prior to the baseline visit.
Invasive Candidiasis, Mucocutaneous Candidiasis, Coccidioidomycosis, Histoplasmosis, Blastomycosis, Chronic Pulmonary Aspergillosis, Allergic Bronchopulmonary Aspergillosis, Invasive Pulmonary Aspergillosis, Recurrent Vulvovaginal Candidiasis, Other Emerging Fungi, Fungi [B01]
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Letrozole With or Without Paclitaxel and Carboplatin in Treating Patients With Stage II-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

This phase III trial studies how well letrozole with or without paclitaxel and carboplatin works in treating patients with stage II-IV low-grade serous carcinoma of the ovary, fallopian tube, or peritoneum. Letrozole is an enzyme inhibitor that lowers the amount of estrogen made by the body which in turn may stop the growth of tumor cells that need estrogen to grow. Drugs used in chemotherapy, such as paclitaxel and carboplatin, 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. It is not yet known whether giving letrozole alone or in combination with paclitaxel and carboplatin works better in treating patients with low-grade serous carcinoma of the ovary, fallopian tube, or peritoneum compared to paclitaxel and carboplatin without letrozole.
Lisa Barroilhet, MD
Female
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04095364
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Inclusion Criteria:

• Patients must have the psychological ability and general health that permits completion of the study requirements and required follow up
• All women will, by definition, be considered menopausal due to surgical removal of both ovaries prior to trial enrollment
• Patients must have newly diagnosed, stage II-IV low-grade serous ovarian cancer (submission of pathology report[s] required). Ovarian cancer = ovarian, fallopian tube and primary peritoneal cancers. p53 immunohistochemistry (IHC) is required and must show nonaberrant pattern (nonaberrant p53 expression is consistent with normal/wildtype TP53). If aberrant p53 expression is found on p53 IHC, the patient is NOT eligible (aberrant p53 expression is consistent with mutant TP53 and supports diagnosis of high grade serous ovarian cancer). A copy of the pathology report that includes the diagnosis of low grade serous ovarian cancer and nonaberrant p53 IHC result must be submitted in RAVE
• Appropriate stage for study entry based on the following diagnostic workup:
• History/physical examination within 14 days prior to registration
• Contrast-enhanced imaging of the chest, abdomen and pelvis within 28 days prior to registration
• Patients must have undergone an attempt at maximal upfront cytoreductive surgery, with either optimal (=< 1 cm diameter residual disease/nodule) or suboptimal residual disease (> 1 cm diameter residual disease/nodule) status allowed
• Patients must have undergone a bilateral salpingo-oophorectomy
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 within 14 days prior to registration
• Patients must be within =< 8 weeks of primary cytoreductive surgery at time of randomization
• Patients must be able to take per oral (P.O.) medications
• Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl (within 14 days prior to registration)
• Platelets greater than or equal to 100,000 cells/mcl (within 14 days prior to registration)
• Creatinine less than or equal to 1.5 x upper limit of normal (ULN) (within 14 days prior to registration)
• Bilirubin less than or equal to 1.5 x ULN (within 14 days prior to registration)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 3 x ULN (within 14 days prior to registration)
• 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:

• 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 may not have received neoadjuvant chemotherapy or radiotherapy for the treatment of this disease
• Patients may not have received previous hormonal therapy for the treatment of this disease
• Patients with known hypersensitivity to letrozole or hypersensitivity/intolerance to carboplatin/paclitaxel therapy
• Patients with severe cardiac disease:
• Myocardial infarction or unstable angina within 6 months prior to registration
• New York Heart Association (NYHA) class II or greater congestive heart failure
• Patients with known central nervous system metastases
• Patients with active (except for uncomplicated urinary tract infection) or uncontrolled systemic infection
• Patients with >= grade 2 baseline neuropathy
• Known human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
Ovary, Low Grade Fallopian Tube Serous Adenocarcinoma, Low Grade Ovarian Serous Adenocarcinoma, Primary Peritoneal Low Grade Serous Adenocarcinoma, Stage II Fallopian Tube Cancer AJCC v8, Stage II Ovarian Cancer AJCC v8, Stage II Primary Peritoneal Cancer AJCC v8, Stage IIA Fallopian Tube Cancer AJCC v8, Stage IIA Ovarian Cancer AJCC v8, Stage IIA Primary Peritoneal Cancer AJCC v8, Stage IIB Fallopian Tube Cancer AJCC v8, Stage IIB Ovarian Cancer AJCC v8, Stage IIB Primary Peritoneal Cancer AJCC v8, Stage III Fallopian Tube Cancer AJCC v8, Stage III Ovarian Cancer AJCC v8, Stage III Primary Peritoneal Cancer AJCC v8, Stage IIIA Fallopian Tube Cancer AJCC v8, Stage IIIA Ovarian Cancer AJCC v8, Stage IIIA Primary Peritoneal Cancer AJCC v8, Stage IIIA1 Fallopian Tube Cancer AJCC v8, Stage IIIA1 Ovarian Cancer AJCC v8, Stage IIIA2 Fallopian Tube Cancer AJCC v8, Stage IIIA2 Ovarian Cancer AJCC v8, Stage IIIB Fallopian Tube Cancer AJCC v8, Stage IIIB Ovarian Cancer AJCC v8, Stage IIIB Primary Peritoneal Cancer AJCC v8, Stage IIIC Fallopian Tube Cancer AJCC v8, Stage IIIC Ovarian Cancer AJCC v8, Stage IIIC Primary Peritoneal Cancer AJCC v8, Stage IV Fallopian Tube Cancer AJCC v8, Stage IV Ovarian Cancer AJCC v8, Stage IV Primary Peritoneal Cancer AJCC v8, Stage IVA Fallopian Tube Cancer AJCC v8, Stage IVA Ovarian Cancer AJCC v8, Stage IVA Primary Peritoneal Cancer AJCC v8, Stage IVB Fallopian Tube Cancer AJCC v8, Stage IVB Ovarian Cancer AJCC v8, Stage IVB Primary Peritoneal Cancer AJCC v8
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Testing the Addition of the Immunotherapy Drug Pembrolizumab to the Usual Chemotherapy Treatment (Paclitaxel and Carboplatin) in Stage III-IV or Recurrent Endometrial Cancer

This phase III trial studies how well the combination of pembrolizumab, paclitaxel and carboplatin works compared with paclitaxel and carboplatin alone in treating patients with endometrial cancer that is stage III or IV, or has come back (recurrent). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Paclitaxel and carboplatin are chemotherapy drugs used as part of the usual treatment approach for this type of cancer. This study aims to assess if adding immunotherapy to these drugs is better or worse than the usual approach for treatment of this cancer.
Lisa Barroilhet, MD
Female
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT03914612
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Inclusion Criteria:

• Measurable stage III, measurable stage IVA, stage IVB (with or without measurable disease) or recurrent (with or without measurable disease) endometrial cancer.
• Pathology report showing results of institutional MMR IHC testing. (This requirement does not apply to sites in Japan.).
• Histologic confirmation of the original primary tumor is required (submission of pathology report(s) is required). Patients with the following histologic types are eligible: Endometrioid adenocarcinoma, serous adenocarcinoma, dedifferentiated/undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.).
• Submission of tumor specimens for centralized MMR IHC testing is required after Step 1 and before Step 2 registration.
• In patients with measurable disease, lesions will be defined and monitored by RECIST version (v) 1.1. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be >= 10 mm when measured by computed tomography (CT) or magnetic resonance imaging (MRI). Lymph nodes must be >= 15 mm in short axis when measured by CT or MRI.
• Patients may have received
• NO prior chemotherapy for treatment of endometrial cancer OR
• Prior adjuvant chemotherapy (e.g., paclitaxel/carboplatin alone or as a component of concurrent chemotherapy and radiation therapy [with or without cisplatin]) provided adjuvant chemotherapy was completed >= 12 months prior to STEP 2 registration.
• Patients may have received prior radiation therapy for treatment of endometrial cancer. Prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para aortic radiation therapy, intravaginal brachytherapy and/or palliative radiation therapy. All radiation therapy must be completed at least 4 weeks prior to STEP 2 registration.
• Patients may have received prior hormonal therapy for treatment of endometrial cancer. All hormonal therapy must be discontinued at least three weeks prior to STEP 2 registration.
• Performance status of 0, 1 or 2.
• Platelets >= 100,000/mcl.
• Absolute neutrophil count (ANC) >= 1,500/mcl.
• Creatinine =< 1.5 x institutional/laboratory upper limit of normal (ULN).
• Total serum bilirubin level =< 1.5 x upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level =< 3 x ULN may be enrolled).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN.
• Thyroid stimulating hormone (TSH) within normal limits (TSH < ULN allowed in euthyroid patients on thyroid replacement therapy).
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of Step 2 registration are eligible for this trial.
• For patients of child bearing potential: negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test is required.
• Administration of study drugs (pembrolizumab, paclitaxel, carboplatin) may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality. Women of childbearing potential (WOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from at least 14 days prior to Step 2 registration (for oral contraceptives), during treatment, and for 120 days after the last dose of study medication. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately. Patients will be considered of nonreproductive potential if they are either:
• Postmenopausal (defined as at least 12 months with no menses without an alternative medical cause; in women < 45 years of age, a high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. In the absence of 12 months of amenorrhea, a single FSH measurement is insufficient); OR
• Have a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation/occlusion, at least 6 weeks prior to Step 2 registration; OR
• Have a congenital or acquired condition that prevents childbearing.
• 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.
• 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:

• Patients with prior treatment with anti-PD-1, anti-PD-L1 or anti-CTLA-4 therapeutic antibody or other similar agents.
• Patients who have a history of a severe hypersensitivity reaction to monoclonal antibody or pembrolizumab (MK-3475) and/or its excipients; and/or a severe hypersensitivity reaction to paclitaxel and/or carboplatin
• Patients who are currently participating and receiving cancer-directed study therapy or have participated in a study of an investigational agent and received cancer-directed study therapy within 4 weeks prior to Step 2 registration.
• Patients who have a diagnosis of immunodeficiency or are receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to Step 2 registration.
• Patients who have received steroids as CT scan contrast premedication may be enrolled.
• The use of inhaled or topical corticosteroids is allowed.
• The use of mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed.
• The use of physiologic doses of corticosteroids may be approved after consultation with the study chair.
• Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression, and they have been off steroids for at least 4 weeks prior to Step 2 registration and remain clinically stable.
• Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. This includes, but is not limited to, patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome because of the risk of recurrence or exacerbation of disease.
• Patients with vitiligo, endocrine deficiencies including type I diabetes mellitus, thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible.
• Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible.
• Patients who have a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis.
• Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection (except for uncomplicated urinary tract infection), interstitial lung disease or active, non-infectious pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; and cirrhosis.
• 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.
• Pregnant or lactating patients.
Corpus Uteri, Uterus, Endometrial Clear Cell Adenocarcinoma, Endometrial Dedifferentiated Carcinoma, Endometrial Endometrioid Adenocarcinoma, Endometrial Mixed Cell Adenocarcinoma, Endometrial Serous Adenocarcinoma, Endometrial Undifferentiated Carcinoma, Recurrent Endometrial Adenocarcinoma, Recurrent Endometrial Carcinoma, Recurrent Endometrial Clear Cell Adenocarcinoma, Recurrent Endometrial Dedifferentiated Carcinoma, Recurrent Endometrial Endometrioid Adenocarcinoma, Recurrent Endometrial Mixed Cell Adenocarcinoma, Recurrent Endometrial Serous Adenocarcinoma, Recurrent Endometrial Undifferentiated Carcinoma, Stage III Uterine Corpus Cancer AJCC v8, Stage IIIA Uterine Corpus Cancer AJCC v8, Stage IIIB Uterine Corpus Cancer AJCC v8, Stage IIIC Uterine Corpus Cancer AJCC v8, Stage IIIC1 Uterine Corpus Cancer AJCC v8, Stage IIIC2 Uterine Corpus Cancer AJCC v8, Stage IV Uterine Corpus Cancer AJCC v8, Stage IVA Uterine Corpus Cancer AJCC v8, Stage IVB Uterine Corpus Cancer AJCC v8
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Study of RP1 Monotherapy and RP1 in Combination With Nivolumab (IGNYTE)

RPL-001-16 is a Phase 1/2, open label, dose escalation and expansion clinical study of RP1 alone and in combination with nivolumab in adult subjects with advanced and/or refractory solid tumors, to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), as well as to evaluate preliminary efficacy.
Hamid Emamekhoo, M.D.
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT03767348
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Inclusion Criteria:

• Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
• At least one measurable and injectable lesion
• Have provided a former tumor pathology specimen or be willing to supply a new tumor sample from a biopsy
• Have a predicted life expectancy of ≥ 3 months
• Measurable disease, according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria
• Subjects with MSI-H or dMMR tumors: has diagnosis of MSI-H or metatstatic dMMR tumor (according to protocol definition) for whom anti PD-1 therapy is indicated, or have refused, become intolerant to or have no further therapy options available
• Subjects with NMSC: has diagnosis of locally advanced or metastatic NMSC that are not considered treatable by surgery including basal cell carcinoma, cutaneous squamous cell carcinoma, basosquamous carcinoma, Merkel cell carcinoma and other non-melanoma skin cancers (per protocol) for whom anti-PD1/PD-L1 therapy is indicated, or have refused, become intolerant to or have no further therapy options available
• Subjects with anti-PD1 failed cutaneous melanoma: has confirmed progressive disease while on anti-PD1 treatment for at least 8 weeks and documented BRAF mutation status
• Subjects with anti-PD1 failed NSCLC: has confirmed progressive disease after no more than two prior systemic treatments including anti-PD1/PD-L1 treatment
Exclusion Criteria:

• Prior treatment with an oncolytic therapy
• History of viral infections according to the protocol
• Prior complications with herpes infections
• Chronic use of anti-virals
• Uncontrolled/untreated brain metastasis
• History of interstitial lung disease
• History of non-infectious pneumonitis
• History of clinically significant cardiovascular disease
Anus, Bones and Joints, Brain and Nervous System, Breast, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Ill-Defined Sites, Kaposi's Sarcoma, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung, Melanoma, Skin, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Soft Tissue, Stomach, Thyroid, Unknown Sites, Urinary Bladder, Head and Neck, Gastrointestinal cancers, other, Colon and Rectum, Anal, Sarcoma, Melanoma/Skin cancer, Uterus, Genitourinary cancers, other, Bladder, Brain/Central Nervous System, Endocrine cancers, Cancer, Melanoma (Skin), Mismatch Repair Deficiency, Microsatellite Instability, Non-melanoma Skin Cancer, Cutaneous Melanoma, NSCLC
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Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)

This phase II Pediatric MATCH trial studies how well palbociclib works in treating patients with Rb positive solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with activating alterations (mutations) in cell cycle genes that have spread to other places in the body and have come back or do not respond to treatment. Palbociclib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Kenneth DeSantes, M.D.
All
12 Months to 21 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT03526250
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Inclusion Criteria:

• Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to MATCH to APEC1621I based on the presence of an actionable mutation
• In addition to the actionable mutations, positive Rb expression by immunohistochemistry is required for study enrollment
• Patients must have a body surface area >= 0.87 m^2 at enrollment
• Patients must have radiographically measurable disease at the time of study enrollment; patients with neuroblastoma who do not have measurable disease but have MIBG+ evaluable disease are eligible; measurable disease in patients with CNS involvement is defined as tumor that is measurable in two perpendicular diameters on magnetic resonance imaging (MRI) and visible on more than one slice
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or cerebrospinal fluid (CSF)
• Previously radiated lesions that have not demonstrated clear progression post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age; Note: Neurologic deficits in patients with CNS tumors must have been relatively stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment; if after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive; for agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
• >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
• Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil counts [ANC] counts): >= 7 days after the last dose of agent
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
• Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for growth factors that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
• Stem cell infusions (with or without total body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
• Radiation therapy (XRT)/external beam irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone morrow (BM) radiation
• Note: Radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days after systemically administered radiopharmaceutical therapy
• Patients must not have received prior exposure to palbociclib, ribociclib, abemaciclib or any other CDK4/6 inhibitors
• For patients with solid tumors without known bone marrow involvement:
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
• Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
• Age: 1 to < 2 years; maximum serum creatinine (mg/dL): male 0.6; female 0.6
• Age: 2 to < 6 years; maximum serum creatinine (mg/dL): male 0.8; female 0.8
• Age: 6 to < 10 years; maximum serum creatinine (mg/dL): male 1; female 1
• Age: 10 to < 13 years; maximum serum creatinine (mg/dL): male 1.2; female 1.2
• Age: 13 to < 16 years; maximum serum creatinine (mg/dL): male 1.5; female 1.4
• Age: >= 16 years; maximum serum creatinine (mg/dL): male 1.7; female 1.4
• Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L; (for the purpose of this study, the ULN for SGPT is 45 U/L)
• Serum albumin >= 2 g/dL
• Patients must be able to swallow intact capsules
• All patients and/or their parents or legally authorized representatives must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines
Exclusion Criteria:

• Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study treatment; females study participants of child-bearing potential and their partners, should agree to use highly effective forms of contraception for at least 3 weeks after the last dose of palbociclib; male study participants should avoid fathering a child, donating sperm, and should agree to use highly effective forms of contraception for at least 3 months after the last dose of palbociclib
• Concomitant medications
• Corticosteroids: Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Investigational drugs: Patients who are currently receiving another investigational drug are not eligible
• Anti-cancer agents: Patients who are currently receiving other anti-cancer agents are not eligible
• Anti-GVHD agents post-transplant: Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
• CYP3A4 agents: Patients who are currently receiving drugs that are strong inducers or inhibitors of CYP3A4 are not eligible; strong inducers or inhibitors of CYP3A4 should be avoided from 14 days prior to enrollment to the end of the study; Note: CYP3A4 inducing anti-epileptic drugs and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed
• Patients who have an uncontrolled infection are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
Anus, Bones and Joints, Brain and Nervous System, Breast, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Hodgkin's Lymphoma, Ill-Defined Sites, Kidney, Larynx, Leukemia, other, Lip, Oral Cavity and Pharynx, Liver, Lung, Lymphoid Leukemia, Melanoma, Skin, Multiple Myeloma, Myeloid and Monocytic Leukemia, Non-Hodgkin's Lymphoma, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Hematopoietic, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Soft Tissue, Stomach, Thyroid, Unknown Sites, Urinary Bladder, Head and Neck, Gastrointestinal cancers, other, Colon and Rectum, Anal, Sarcoma, Melanoma/Skin cancer, Uterus, Genitourinary cancers, other, Bladder, Brain/Central Nervous System, Endocrine cancers, Lymphoma, Leukemia, Hematologic cancers, other, Advanced Malignant Solid Neoplasm, Recurrent Childhood Ependymoma, Recurrent Ewing Sarcoma, Recurrent Glioma, Recurrent Hepatoblastoma, Recurrent Kidney Wilms Tumor, Recurrent Langerhans Cell Histiocytosis, Recurrent Malignant Germ Cell Tumor, Recurrent Malignant Glioma, Recurrent Medulloblastoma, Recurrent Neuroblastoma, Recurrent Non-Hodgkin Lymphoma, Recurrent Osteosarcoma, Recurrent Peripheral Primitive Neuroectodermal Tumor, Recurrent Rhabdoid Tumor, Recurrent Rhabdomyosarcoma, Recurrent Soft Tissue Sarcoma, Refractory Ependymoma, Refractory Ewing Sarcoma, Refractory Glioma, Refractory Hepatoblastoma, Refractory Langerhans Cell Histiocytosis, Refractory Malignant Germ Cell Tumor, Refractory Malignant Glioma, Refractory Medulloblastoma, Refractory Neuroblastoma, Refractory Non-Hodgkin Lymphoma, Refractory Osteosarcoma, Refractory Peripheral Primitive Neuroectodermal Tumor, Refractory Rhabdoid Tumor, Refractory Rhabdomyosarcoma, Refractory Soft Tissue Sarcoma
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Regional Radiotherapy in Biomarker Low-Risk Node Positive and T3N0 Breast Cancer (TAILOR RT)

The purpose of this study is to compare the effects on low risk breast cancer receiving usual care that includes regional radiation therapy, with receiving no regional radiation therapy. Researchers want to see if not giving this type of radiation treatment works as well at preventing breast cancer from coming back.
Bethany Anderson, MD
Female
35 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT03488693
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Inclusion Criteria:

• Patients must be women with newly diagnosed histologically proven invasive carcinoma of the breast with no evidence of metastases, staged as per site standard of care.
• Patients must have been treated by BCS or mastectomy with clear margins of excision. Post-mastectomy positive margins for invasive disease and/or DCIS is not allowed. Multifocal disease (i.e. the presence of two or more foci or breast cancer within the same breast quadrant) and multicentric disease (i.e. the presence of two or more foci of breast cancer in different quadrants of the same breast) are allowed.
• Patients with T3N0 disease are eligible.
• Patients with disease limited to nodal micrometastases are not eligible
• Patients with nodal macrometastases (>2mm) treated by axillary dissection must have 1-3 positive axillary nodes (macrometastases, > 2 mm).
• Patients treated by mastectomy and SLNB alone must have only 1 positive axillary node (macrometastases, > 2 mm).
• Patients must be ER ≥ 1% and HER2 negative on local testing
• Patients must have an Oncotype DX recurrence score • Patient must consent to provision of, and investigator(s) must agree to submit to the CCTG Central Tumour Bank, a representative formalin fixed paraffin block of tumour tissue in order that the specific correlative marker assays described in the protocol may be conducted
• Patient must consent to provision of samples of blood in order that the specific correlative marker assays described in the protocol may be conducted.
• Patients must have had endocrine therapy initiated or planned for ≥ 5 years. Premenopausal women will receive ovarian ablation plus aromatase inhibitor therapy or tamoxifen if adjuvant chemotherapy was not administered. For all patients, endocrine therapy can be given concurrently or following RT.
• Patients may or may not have had adjuvant chemotherapy.
• RT must be administered within 16 weeks of definitive surgery if the patient is not treated with chemotherapy. If adjuvant chemotherapy is given, RT must begin within 12 weeks after the last dose. (Note: adjuvant chemotherapy may be ongoing at the time of randomization). Definitive surgery is defined as the last breast cancer-related surgery.
• Patient's ECOG performance status must be 0, 1 or 2.
• Patient's age must be ≥ 35 years.
• For the first 736 eligible English or French-speaking subjects who have agreed to optional questionnaire completion: Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life, health utilities and lost productivity questionnaires in either English or French
• Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements
• Patients must be accessible for treatment and follow-up. Investigators must assure themselves the patients randomized on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.
• In accordance with CCTG policy, protocol treatment is to begin within 3 weeks of patient randomization.
• Women of childbearing potential must have agreed to use an effective contraceptive method. A woman is considered to be of "childbearing potential" if she has had menses at any time in the preceding 12 consecutive months.
Exclusion Criteria:

• Patients with nodal disease limited to isolated tumour cells (pN0i+ < 0.2 mm).
• Patients with pT3N1 and pT4 disease (Note: patients with T3N0) are eligible.
• Any prior history, not including the index cancer, of ipsilateral invasive breast cancer or ipsilateral DCIS treated with radiation therapy. (Patients with synchronous or previous ipsilateral LCIS are eligible.)
• Synchronous or previous contralateral invasive breast cancer. (Patients with contralateral DCIS are eligible unless previously treated with radiation.)
• History of non-breast malignancies except adequately treated non-melanoma skin cancers, in situ cancers treated by local excision or other cancers curatively treated with no evidence of disease for ≥ 5 years.
• Patients who are pregnant.
• Patients that have had prior ipsilateral chestwall/thoracic radiation.
• Patients treated with chemo or endocrine therapy administered in the neoadjuvant setting for breast cancer. Endocrine therapy exposure 12 weeks or less prior to surgery is permitted.
• Patients with serious non-malignant disease (e.g. cardiovascular, scleroderma etc.) which would preclude RT.
• Patients with any serious active or co-morbid medical conditions, laboratory abnormality, psychiatric illness, active or uncontrolled infections, or serious illnesses or medical conditions that would prevent the patient from participating or to be managed according to the protocol (according to investigator's decision).
Breast Cancer, Breast
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Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer

This randomized phase III trial studies how well hypofractionated radiation therapy works in preventing recurrence in patients with stage IIa-IIIa cancer who have undergone mastectomy. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells that remain after surgery and have fewer side effects.
Bethany Anderson, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT03414970
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Inclusion Criteria:

• Histologically confirmed invasive carcinoma of the breast of any of the following histologies (ductal, lobular, mammary, medullary, or tubular); patients with metaplastic breast cancer are not eligible
• Patients will be staged according to the TNM staging system
• For patients not receiving neoadjuvant chemotherapy, pathologic staging must be T0N1-2a, T1N1-2a, T2N1-2a, T3N0-2a, and all M0 status
• For patients receiving neoadjuvant chemotherapy, clinical pre-chemo staging and post mastectomy pathological staging is required for all patients; patients who have received neoadjuvant chemotherapy and are pathologically cT0-2 and N0 are only eligible if biopsy-proven clinically N1 or N2 disease is documented prior to the start of neoadjuvant chemotherapy; cT3N0 patients or ypT3N0 patients who receive neoadjuvant chemotherapy may be eligible based on clinical or pathological T stage, and do not require pathologically positive lymph nodes
• Note: Higher of the clinical or pathological T and N stage are used for final staging, if receiving neoadjuvant chemotherapy; all patients with clinical, radiographic or pathological T4, N3 or involved internal mammary disease (N1b, N1c, and N2b) are not eligible. N1mic patients are eligible.
• No prior therapeutic radiation therapy to the chest, neck or axilla; prior radioactive oral iodine is permitted
• No prior history of ipsilateral breast cancer (invasive disease or ductal breast carcinoma in situ [DCIS]); lobular carcinoma in situ (LCIS) and benign breast disease is allowed
• No history of prior or concurrent contralateral invasive breast cancer; benign breast disease, LCIS or DCIS of contralateral breast is allowed
• No active collagen vascular diseases, such as: systemic lupus erythematous, scleroderma, or dermatomyositis
• Negative inked histologic margins from mastectomy pathology (no invasive cells at margin). Patients with DCIS at margin are eligible.
• No significant post mastectomy complications in the ipsilateral breast requiring an unplanned re-operation or admission for intravenous (IV) antibiotics; re-operation for margins evaluation, nodal completion and routine reconstruction is acceptable
• Radiation oncologist intends to treat all target volumes and respect all normal tissues in accordance with the dosimetric constraints described (simulation before registration recommended)
• Radiation oncologist is planning to treat regional lymph nodes including internal mammary nodes and meet acceptable protocol dosimetric requirements
• Radiation oncologist is NOT planning to utilize a chest wall/scar boost
• Patient must have undergone immediate reconstruction at the time of mastectomy or be planning to undergo reconstruction within 18 months after radiation
• Treating physician and patient must plan to start radiation treatment within the timeframes specified in protocol.
• If a tissue expander is utilized it needs to be a fluid filled expander, NO air expander (unless completely deflated) during radiation therapy
• For patients with diabetes, hemoglobin A1C test must have been performed =< 90 days prior to registration
• No co-existing medical conditions with life expectancy < 5 years
• No other malignancy within 5 years of registration with the exception of basal cell or squamous cell carcinoma of the skin treated with local resection only or carcinoma in situ of the cervix
• Negative pregnancy test (serum or urine HCG) in women of child-bearing potential ≤ 7 days prior to registration. Patients who have received a bilateral tubal ligation still require a negative pregnancy test for eligibility. A female of childbearing potential is a sexually mature female who has not undergone a hysterectomy or bilateral oophorectomy and has not been naturally postmenopausal for at least 12 consecutive months
• Women of child-bearing potential must agree to utilize a form of birth control or agree to undergo sexual abstinence during radiation therapy
• Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status 0-1
• Patients must be able to read and comprehend English, in order to be able to complete study questionnaires; however, patients participating through Canadian Cancer Trials Group (CCTG) institutions who can read and comprehend French are eligible
Ductal Breast Carcinoma, Invasive Breast Carcinoma, Lobular Breast Carcinoma, Medullary Breast Carcinoma, Stage II Breast Cancer, Stage IIA Breast Cancer, Stage IIB Breast Cancer, Stage IIIA Breast Cancer, Tubular Breast Carcinoma, Breast
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Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)

This phase II Pediatric MATCH trial studies how well olaparib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with defects in deoxyribonucleic acid (DNA) damage repair genes that have spread to other places in the body (advanced) and have come back (relapsed) or do not respond to treatment (refractory). Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Kenneth DeSantes, M.D.
All
12 Months to 21 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT03233204
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Inclusion Criteria:

• Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to Molecular Analysis for Therapy Choice (MATCH) to APEC1621H based on the presence of an actionable mutation
• Patients must have a body surface area >= 0.65 m^2 at enrollment
• Patients must have radiographically measurable disease at the time of study enrollment; patients with neuroblastoma who do not have measurable disease but have iobenguane (MIBG) positive (+) evaluable disease are eligible; measurable disease in patients with CNS involvement is defined as tumor that is measurable in two perpendicular diameters on magnetic resonance imaging (MRI) and visible on more than one slice
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or cerebrospinal fluid (CSF)
• Previously radiated lesions that have not demonstrated clear progression post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age
• Note: Neurologic deficits in patients with CNS tumors must have been relatively stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment; if after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive
• >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
• Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
• Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for growth factors that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
• Stem cell infusions (with or without total body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
• Radiation therapy (XRT)/external beam irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation
• Note: Radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131iodine [I]-MIBG): >= 42 days after systemically administered radiopharmaceutical therapy
• Patients must not have received prior exposure to olaparib, veliparib, niraparib, rucaparib, talazoparib or other poly adenosine diphosphate ribose polymerase inhibitors (PARPi)
• For patients with solid tumors without known bone marrow involvement: peripheral absolute neutrophil count (ANC) >= 1000/mm^3 (within 7 days prior to enrollment)
• For patients with solid tumors without known bone marrow involvement: platelet count >= 100,000/mm^3 (within 7 days prior to enrollment) (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
• Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive platelet or packed red blood cells [pRBC] transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 (within 7 days prior to enrollment) or
• A serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
• Age 1 to < 2 years: maximum serum creatinine 0.6 mg/dL for male and 0.6 mg/dL for female
• Age 2 to < 6 years: maximum serum creatinine 0.8 mg/dL for male and 0.8 mg/dL for female
• Age 6 to < 10 years: maximum serum creatinine 1 mg/dL for male and 1 mg/dL for female
• Age 10 to < 13 years: maximum serum creatinine 1.2 mg/dL for male and 1.2 mg/dL for female
• Age 13 to < 16 years: maximum serum creatinine 1.5 mg/dL for male and 1.4 mg/dL for female
• Age >= 16 years: maximum serum creatinine 1.7 mg/dL for male and 1.4 mg/dL for female
• Patients with solid tumors: bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
• Patients with solid tumors: serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (within 7 days prior to enrollment); (for the purpose of this study, the ULN for SGPT is 45 U/L)
• Patients with solid tumors: serum albumin >= 2 g/dL (within 7 days prior to enrollment)
• Activated partial thromboplastin time (aPTT) =< 1.5 x ULN (within 7 days prior to enrollment)
• International normalized ratio (INR) =< 1.5 (within 7 days prior to enrollment)
• Patients must be able to swallow intact tablets
• All patients and/or their parents or legally authorized representatives must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines
Exclusion Criteria:

• Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies; pregnancy tests must be obtained in girls who are post-menarchal; women of child-bearing potential and their partners should agree to use two (2) highly effective forms of contraception throughout study participation and for at least one (1) month after the last dose of olaparib; male study participants should avoid fathering a child or donating sperm during the study and for three (3) months after the last dose of olaparib
• Concomitant medications
• Corticosteroids: patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Investigational drugs: patients who are currently receiving another investigational drug are not eligible
• Anti-cancer agents: patients who are currently receiving other anti-cancer agents are not eligible
• Anti-GVHD agents post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
• CYP3A/CYP3A4 agents: patients who are currently receiving drugs that are strong and moderate inducers or inhibitors of CYP3A or CYP3A4 are not eligible; strong inducers or inhibitors of CYP3A4 should be avoided from 21 days prior to enrollment to the end of the study
• Patients who have an uncontrolled infection are not eligible
• Patient who are known to be serologically positive for human immunodeficiency virus (HIV)
• Patients with known active hepatitis (i.e. hepatitis B or C)
• Patients who have received a prior solid organ transplantation are not eligible
• Patients with symptomatic uncontrolled brain metastases; a scan to confirm the absence of brain metastases is not required; the patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to enrollment; patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days
• Patients with known symptomatic Fanconi anemia (FA), ataxia-telangiectasia (A-T) syndrome, Bloom syndrome (BS) and Nijmegen breakage syndrome (NBS) are not eligible (asymptomatic carriers are acceptable)
• Major surgery must not have occurred within 2 weeks prior to enrollment and patients must have recovered from any effects of any major surgery
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
Advanced Malignant Solid Neoplasm, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Low Grade Glioma, Malignant Glioma, Recurrent Childhood Central Nervous System Neoplasm, Recurrent Childhood Ependymoma, Recurrent Childhood Malignant Germ Cell Tumor, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Rhabdomyosarcoma, Recurrent Childhood Soft Tissue Sarcoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Recurrent Glioma, Recurrent Hepatoblastoma, Recurrent Langerhans Cell Histiocytosis, Recurrent Malignant Solid Neoplasm, Recurrent Medulloblastoma, Recurrent Neuroblastoma, Recurrent Osteosarcoma, Refractory Childhood Malignant Germ Cell Tumor, Refractory Ependymoma, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Glioma, Refractory Hepatoblastoma, Refractory Langerhans Cell Histiocytosis, Refractory Malignant Glioma, Refractory Malignant Solid Neoplasm, Refractory Medulloblastoma, Refractory Neuroblastoma, Refractory Non-Hodgkin Lymphoma, Refractory Osteosarcoma, Refractory Primary Central Nervous System Neoplasm, Refractory Rhabdomyosarcoma, Refractory Soft Tissue Sarcoma, Rhabdoid Tumor, Wilms Tumor, Anus, Any Site, Bones and Joints, Brain and Nervous System, Breast, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Hodgkin's Lymphoma, Ill-Defined Sites, Kaposi's Sarcoma, Kidney, Larynx, Leukemia, other, Lip, Oral Cavity and Pharynx, Liver, Lung, Lymphoid Leukemia, Melanoma, Skin, Multiple Myeloma, Mycosis Fungoides, Myeloid and Monocytic Leukemia, Non-Hodgkin's Lymphoma, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Hematopoietic, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Soft Tissue, Stomach, Thyroid, Unknown Sites, Urinary Bladder, Head and Neck, Gastrointestinal cancers, other, Colon and Rectum, Anal, Sarcoma, Melanoma/Skin cancer, Hematologic cancers, other, Uterus, Genitourinary cancers, other, Bladder, Brain/Central Nervous System, Endocrine cancers, Lymphoma, Leukemia
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Digital Tomosynthesis Mammography and Digital Mammography in Screening Patients for Breast Cancer

This randomized phase III trial studies digital tomosynthesis mammography and digital mammography in screening patients for breast cancer. Screening for breast cancer with tomosynthesis mammography may be superior to digital mammography for breast cancer screening and may help reduce the need for additional imaging or treatment.
Mai Elezaby, MD
Female
45 Years to 74 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT03233191
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Inclusion Criteria:

• Women of childbearing potential must not be known to be pregnant or lactating
• Patients must be scheduled for, or have intent to schedule, a screening mammogram
• Patients must be able to tolerate digital breast tomosynthesis and full-field digital mammographic imaging required by protocol, to be performed at an American College of Radiology Imaging Network (ACRIN)-qualified facility
• Patients must be willing and able to provide a written informed consent
• Patients must not have symptoms or signs of benign or malignant breast disease (eg, nipple discharge, breast lump) warranting a diagnostic rather than a screening mammogram, and/or other imaging studies (eg, sonogram); patients with breast pain are eligible as long as other criteria are met
• Patients must not have had a screening mammogram within the last 11 months prior to date of randomization
• Patients must not have previous personal history of breast cancer including ductal carcinoma in situ
• Patients must not have breast enhancements (e.g., implants or injections)
• ANNUAL SCREENING REGIMEN ELIGIBILITY CHECK
• To be eligible for inclusion in the annual screening regimen one of the following three conditions must be met in addition to the eligibility criteria above:
• Patients are pre-menopausal; OR
• Post-menopausal aged 45-69 with any of the following three risks factors:
• Dense breasts (BIRADS density categories c-heterogeneously dense or d-extremely dense), or
• Family history of breast cancer (first degree relative with breast cancer), or, positive genetic testing for any deleterious genes that indicate an increased risk for breast cancer, or
• Currently on hormone therapy; OR
• Post-menopausal ages 70-74 with either of the following two risk factors:
• Dense breasts (BIRADS density categories c-heterogeneously dense or d-extremely dense), or
• Currently on hormone therapy
• Postmenopausal women are defined as those with their last menstrual period more than 12 months prior to study entry; for the purpose of defining menopausal status for women who have had surgical cessation of their periods, women who no longer have menses due to hysterectomy and oophorectomy will be considered postmenopausal; women who no longer have menses due to hysterectomy without oophorectomy will be considered premenopausal until age 52 and postmenopausal thereafter
• All other postmenopausal women are eligible for inclusion in the biennial screening regimen
• For those women who cannot be assigned to annual or biennial screening at the time of study entry and randomization because they are postmenopausal, have no family history or known deleterious breast cancer mutation, are not on hormone therapy AND have not had a prior mammogram, breast density will be determined by the radiologist?s recording of it at the time of interpretation of the first study screening examination, either DM or TM; for those who are randomized to TM, radiologists will assign BI-RADS density through review of the DM or synthetic DM portion of the TM examination; such women cannot be part of the planned stratification by screening frequency and are expected to represent far less than 1% of the Tomosynthesis Mammographic Imaging Screening Trial (TMIST) population
• Breast density will be determined by prior mammography reports, when available; all other risk factors used to determine patient eligibility for annual or biennial screening will be determined by subject self-report
Breast Screening, Malignant neoplasms of breast
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Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial)

This phase II Pediatric MATCH trial studies how well vemurafenib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with BRAF V600 mutations that have spread to other places in the body (advanced) and have come back (recurrent) or do not respond to treatment (refractory). Vemurafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Kenneth DeSantes, M.D.
All
12 Months to 21 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT03220035
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Inclusion Criteria:

• Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to Molecular Analysis for Therapy Choice (MATCH) to APEC1621G based on the presence of a BRAF V600 mutation
• Patients must have a body surface area >= 0.55 m^2 at enrollment; patients < 0.73 m^2 must follow the dosing nomogram; patients >= 0.73 m^2 at enrollment must follow the dosing nomogram
• Patients must have radiographically measurable disease at the time of study enrollment; patients with neuroblastoma who do not have measurable disease but have metaiodobenzylguanidine (MIBG) positive (+) evaluable disease are eligible; measurable disease in patients with CNS involvement is defined as tumor that is measurable in two perpendicular diameters on magnetic resonance imaging (MRI) and visible on more than one slice; Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or cerebrospinal fluid (CSF)
• Previously radiated lesions that have not demonstrated clear progression post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age; Note: Neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment; if after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive
• >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
• Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
• Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for growth factors that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
• Stem cell Infusions (with or without total-body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
• Radiation therapy (XRT)/external beam irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation; Note: Radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, iobenguane I-131 [131I-MIBG]): >= 42 days after systemically administered radiopharmaceutical therapy
• Patients must not have received prior exposure to a BRAF inhibitor (e.g. vemurafenib, dabrafenib or encorafenib)
• For patients with solid tumors without known bone marrow involvement:
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
• Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts in above criteria (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
• Age: 1 to < 2 years; maximum serum creatinine (mg/dL): male 0.6; female 0.6
• Age: 2 to < 6 years; maximum serum creatinine (mg/dL): male 0.8; female 0.8
• Age: 6 to < 10 years; maximum serum creatinine (mg/dL): male 1; female 1
• Age: 10 to < 13 years; maximum serum creatinine (mg/dL): male 1.2; female 1.2
• Age: 13 to < 16 years; maximum serum creatinine (mg/dL): male 1.5; female 1.4
• Age: >= 16 years; maximum serum creatinine (mg/dL): male 1.7; female 1.4
• Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L; (for the purpose of this study, the ULN for SGPT is 45 U/L)
• Serum albumin >= 2 g/dL
• Corrected QT (QTc) interval =< 480 milliseconds; Note: Patients should avoid concomitant medication known or suspected to prolong QTc interval or cause Torsades De Pointes; if possible, alternative agents should be considered; patients who are receiving drugs that prolong the QTc are eligible if the drug is necessary and no alternatives are available
• Patients must be able to swallow intact tablets
• All patients and/or their parents or legally authorized representatives must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines
Exclusion Criteria:

• Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method, for the duration of study treatment and for 6 months after the last dose of vemurafenib
• Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Patients who are currently receiving another investigational drug are not eligible
• Patients who are currently receiving other anti-cancer agents are not eligible
• Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
• Patients who are currently receiving drugs that are moderate to strong inducers or inhibitors of CYP3A4 are not eligible; moderate to strong inducers or inhibitors of CYP3A4 should be avoided from 14 days prior to enrollment to the end of the study; Note: CYP3A4 inducing anti-epileptic drugs and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed
• Patients who are currently receiving drugs that are inhibitors or inducers of p-glycoprotein (P-gp) or adenosine triphosphate (ATP)-binding cassette, subfamily G, member 2 (ABCG2 [BCRP]) are not eligible
• Patients with known active cutaneous squamous cell carcinoma (includes keratoacanthoma or mixed keratoacanthoma subtype) are not eligible; patients who have fully excised lesions with dermatologic confirmation of absence of disease are eligible
• Patients with low grade glioma patients (World Health Organization [WHO] grades I and II) are not eligible
• Patients who have an uncontrolled infection are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
Advanced Malignant Solid Neoplasm, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Ependymoma, Ewing Sarcoma, Hepatoblastoma, Langerhans Cell Histiocytosis, Malignant Germ Cell Tumor, Malignant Glioma, Osteosarcoma, Peripheral Primitive Neuroectodermal Tumor, Recurrent Childhood Central Nervous System Neoplasm, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Malignant Solid Neoplasm, Recurrent Neuroblastoma, Refractory Malignant Solid Neoplasm, Refractory Neuroblastoma, Refractory Non-Hodgkin Lymphoma, Refractory Primary Central Nervous System Neoplasm, Rhabdoid Tumor, Rhabdomyosarcoma, Soft Tissue Sarcoma, Wilms Tumor, Anus, Any Site, Bones and Joints, Brain and Nervous System, Breast, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Hodgkin's Lymphoma, Ill-Defined Sites, Kaposi's Sarcoma, Kidney, Larynx, Leukemia, other, Lip, Oral Cavity and Pharynx, Liver, Lung, Lymphoid Leukemia, Melanoma, Skin, Multiple Myeloma, Mycosis Fungoides, Myeloid and Monocytic Leukemia, Non-Hodgkin's Lymphoma, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Hematopoietic, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Soft Tissue, Stomach, Thyroid, Unknown Sites, Urinary Bladder, Head and Neck, Gastrointestinal cancers, other, Colon and Rectum, Anal, Sarcoma, Melanoma/Skin cancer, Hematologic cancers, other, Uterus, Genitourinary cancers, other, Bladder, Brain/Central Nervous System, Endocrine cancers, Lymphoma, Leukemia
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