Here are the studies that match your search criteria. If you are interested in participating, please reach out to the contact listed for the study. If no contact is listed, contact us and we'll help you find the right person.
A Study of Nemtabrutinib Plus Venetoclax vs Venetoclax + Rituximab (VR) in Second-line (2L) + Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (MK-1026-010/BELLWAVE-010)
The purpose of this study is to assess the safety and tolerability and to confirm the dose of
nemtabrutinib in combination with venetoclax in participants with R/R CLL/SLL. The primary
study hypotheses are that the combination of nemtabrutinib plus venetoclax is superior to VR
with respect to progression-free survival (PFS) per 2018 International Workshop on Chronic
Lymphocytic Leukemia (iwCLL) criteria as assessed by blinded independent central review
(BICR).
Christopher Fletcher, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05947851
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Inclusion Criteria:
• Confirmed diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma
(CLL/SLL) and active disease clearly documented to initiate therapy.
• Deletion (Del) (17p) status, tumor protein 53 (TP53) mutation status, immunoglobulin
heavy chain gene (IGHV) mutation status and Bruton's tyrosine kinase (BTK)-C481
mutation status results required before randomization for Part 2 participants only.
• Relapsed or refractory to at least 1 prior available therapy.
• Have at least 1 marker of disease burden.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 within 7
days before randomization.
• Has a life expectancy of at least 3 months.
• Has the ability to swallow and retain oral medication.
• Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they
have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have
undetectable HBV deoxyribonucleic acid (DNA) viral load before randomization.
• Participants with history of hepatitis C virus (HCV) infection are eligible if HCV
ribonucleic acid (RNA) viral load is undetectable at screening.
• Participants with human immunodeficiency virus (HIV) who meet ALL eligibility
criteria.
• Participants with adequate organ function with specimens collected within 7 days
before the start of study intervention.
• If capable of producing sperm, participant agrees to eliminate Nemtabrutinib: 12 days,
Venetoclax: 1 month (30 days), Rituximab (rituximab biosimilar): not applicable;
abstains from penile-vaginal intercourse as their preferred and usual lifestyle; OR
uses prescribed contraception.
• Participant assigned female sex at birth are eligible to participate if not pregnant
or breastfeeding and are not a person of childbearing potential (POCBP) OR is a POCBP
and uses a contraceptive method that is highly effective, has a negative highly
sensitive pregnancy test, and abstains from breastfeeding.
Exclusion Criteria:
• Has an active hepatitis B virus/ hepatitis C virus (HBV/HCV) infection.
• Has gastrointestinal (GI) dysfunction that may affect drug absorption.
• Has a known additional malignancy that is progressing or has required active treatment
within the past 3 years.
• Has diagnosis of Richter Transformation or active central nervous system (CNS)
involvement by CLL/SLL.
• Has an active infection requiring systemic therapy, such as intravenous (IV)
antibiotics, during screening.
• HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric
Castleman's Disease and/or acquired immune deficiency syndrome (AIDS)-defining
opportunistic infection in the past 12 months before screening.
• Has QT interval corrected (QTc) prolongation or other significant electrocardiogram
(ECG) abnormalities.
• Has a known allergy/sensitivity to nemtabrutinib or contraindication to
venetoclax/rituximab (or rituximab biosimilar), or any of the excipients.
• Has history of severe bleeding disorders (eg, hemophilia).
• Has received prior systemic anticancer therapy within 5 half-lives or 4 weeks (if
prior therapy was a monoclonal antibody) before randomization.
• Has received prior B-cell lymphoma 2 inhibitor(s) (BCL2i) including venetoclax or
Non-covalent Bruton's tyrosine kinase inhibitor (BTKi).
• Is currently being treated with p-glycoprotein (P-gp) substrates with a narrow
therapeutic index, cytochrome P450 3A (CYP3A) strong or moderate inducers or CYP3A
strong inhibitors.
• Has received a live or live attenuated vaccine within 30 days before the first dose of
study intervention.
• Has received an investigational agent or has used an investigational device within 4
weeks before study intervention administration.
• Has a known psychiatric or substance use disorder that would interfere with the
participant's ability to cooperate with the requirements of the study.
• Participants who have not adequately recovered from major surgery or have ongoing
surgical complications.
A Study of PARG Inhibitor IDE161 in Participants With Advanced Solid Tumors
The purpose of this study is to characterize the safety, tolerability, and efficacy of
IDE161.
Mark Burkard, MD, PhD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT05787587
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Inclusion Criteria:
1. Adult participants must be 18 years of age or older
2. Advanced or metastatic solid tumors excluding primary central nervous system (CNS)
tumors
3. Have documented evidence of genetic alterations conferring homologous recombination
deficiency
4. Participant must have progressed on at least one prior line of therapy in the advanced
or metastatic setting that is considered an appropriate standard of care, or for which
the participant has documented intolerance
Exclusion Criteria:
1. Known primary CNS malignancy
2. Impairment of GI function or GI disease that may significantly alter the absorption of
IDE161
3. Have active, uncontrolled infection
4. Clinically significant cardiac abnormalities
5. Major surgery within 4 weeks prior to enrollment
6. Radiation therapy within 2 weeks prior to enrollment
7. Systemic cytotoxic chemotherapy within 4 weeks prior to enrollment
8. Radioimmunotherapy within 6 weeks of enrollment
9. Treatment with a therapeutic antibody within 4 weeks prior to enrollment
10. Treatment with an anti-cancer small molecule within 5 half-lives (t1/2), or 2 weeks,
whichever is shorter
Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Mycosis Fungoides, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Melanoma/Skin cancer, Sarcoma, Uterus, Advanced or Metastatic Solid Tumors, Breast Cancer, Ovarian Cancer, Pancreas Cancer, Prostate Cancer
Correlating Early FDG PET/CT and ctDNA in Immune Checkpoint Inhibitor (ICI)-Treated Melanoma Patients
The purpose of this research study is to determine if analysis of PET/CT scans and testing of
blood samples in people with melanoma that has spread in their body can help researchers
determine which patients are more or less likely to respond to immunotherapy and are more or
less likely to have side effects. 24 participants will be enrolled and be on study until
approximately 4 weeks after their first dose of Immune Checkpoint Inhibitor therapy.
Vincent Ma, MD
All
18 Years and over
IV
This study is NOT accepting healthy volunteers
NCT06199713
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Inclusion Criteria:
• Willing to provide informed consent.
• Must have a metastatic melanoma diagnosis (stage IV) for which treatment with
ipilimumab, nivolumab, and/or pembrolizumab, either alone or in combination with other
ICI therapy, is planned.
• Must be planning to participate in Signatera™ (ctDNA level) monitoring with standard
of care laboratory testing routinely obtained for treatment with ICI therapy.
• Individuals at least 18 years of age.
• Women of childbearing potential must be willing to use effective contraception as
discussed with their oncologist while participating in this study.
• Willing to comply with all study procedures and be available for the duration of the
study.
Exclusion Criteria:
• Not able to receive treatment with ICI therapy
• Use of investigational drugs, biologics, or devices within 30 days prior to
enrollment.
• Women who are pregnant, lactating, or planning on becoming pregnant during the study.
• Not suitable for study participation due to other reasons at the discretion of the
investigators.
Melanoma, Melanoma Stage III, Melanoma Stage IV, Unresectable Melanoma, Melanoma, Skin, Other Skin, Melanoma/Skin cancer
Transversus Abdominis Plane Block Compared to Local Anesthetic Wound Infiltration in Gynecologic Oncology Surgery
This study is being done to see if preoperative transversus abdominis plane (TAP) analgesia
will provide similar postoperative pain control, hospital length of stay, and postoperative
outcomes compared to surgeon-initiated wound infiltration with local anesthetic in
participants undergoing laparotomy for gynecologic indications.
Sumer Wallace, M.D.
Female
18 Years and over
Phase 4
This study is NOT accepting healthy volunteers
NCT06213454
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Inclusion Criteria:
• Ability to understand and the willingness to sign a written informed consent document
• Patients undergoing exploratory laparotomy via midline vertical skin incision for
gynecologic indications at UW Hospital and Clinics
• Patients must be >18 years old
• English speaking (able to provide consent and complete questionnaires)
• Patients must have the ability to understand visual and verbal pain scales
• Patients must be eligible for TAP block placement. This will be confirmed during
preoperative visit with the primary surgeon. Patient's are not eligible if they have
allergies to the anesthetic medications or have had prior abdominal reconstructive
surgery that would alter their abdominal wall anatomy in a way where the block would
not be expected to be effective.
Exclusion Criteria:
• Known allergy to local anesthetics.
• Known history of chronic pain disorders and/or chronic opioid use defined as greater
than 10mg of PO morphine or equivalent used daily for at least 30 days prior to
enrollment.
• Patient has a history of opioid dependence requiring rehabilitation or the use of
opioid antagonists.
• Patients with a planned exploration with biopsies (no organs removed) will be excluded
from the study.
• Individuals who are pregnant, lactating or planning on becoming pregnant during the
study.
• Significant liver disease that would inhibit prescription of opioids.
• Significant kidney disease that would inhibit administration of gabapentin.
• Not suitable for study participation due to other reasons at the discretion of the
investigators.
Cervix, Corpus Uteri, Ovary, Other Female Genital, Uterus, Analgesia, Surgery
This pilot comparative effectiveness trial will compare two active smoking cessation
treatments in terms of effectiveness, equity across patient subpopulations, and efficiency
among adult patients diagnosed with cancer within the past 3 years. An enhanced treatment
comprising 12 weeks of varenicline treatment and 7 smoking cessation coaching calls with a
cancer focus will be compared against an active comparator modeled after standard quitline
treatments (2 weeks of nicotine patch therapy with 3 phone coaching calls). Approximately 50
participants will be recruited to generate estimates of the effects, acceptability, costs,
and equity of enhanced treatment (vs. standard treatment), with the primary outcome being
abstinence from smoking 26 weeks after trying to quit.
Danielle Mccarthy
All
18 Years and over
Phase 4
This study is NOT accepting healthy volunteers
NCT06218823
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Inclusion Criteria:
• Alive (per medical record)
• Diagnosed with cancer in the past 3 years
• Received care from a participating oncology clinic in the past year
• Has a current tobacco use status
• Does not have a preferred language other than English (missing language preference
will be included).
• Valid address that is not a correctional facility or residential treatment/care
facility.
• No flag for patient cognitive impairment, activated health care power of attorney, or
other health care agent (e.g., legally authorized representative) in the EHR.
The following additional inclusion criteria must be met for inclusion in the CET
• Smoked combustible cigarettes in the past month.
• Able to speak and understand English.
• Willing to set a date to quit smoking in the next 60 days.
• Willing to receive smoking treatment information.
• Willing to complete study activities.
Exclusion Criteria:
• No current suicidal ideation.
• Suicide attempt in the past year.
• Currently receiving treatment for bipolar disorder, schizophrenia, schizoaffective
disorder, or psychotic disorder.
• Incarceration.
• Unable to provide informed consent to treatment (i.e., cannot answer questions about
study procedures or risks after hearing about the study).
Smoking Cessation, Cancer, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Mycosis Fungoides, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Multiple Myeloma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Leukemia, Lymphoma, Melanoma/Skin cancer, Sarcoma, Uterus
A Study to Investigate the Safety and Efficacy of K-321 Eye Drops After Simultaneous Cataract Surgery and Descemetorhexis in Participants With Fuchs Endothelial Corneal Dystrophy (FECD)
A study to assess the safety and efficacy of K-321 in participants with FECD after
simultaneous cataract surgery and descemetorhexis.
Evan Warner
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05826353
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Inclusion Criteria:
• Is at least 18 years old at the screening visit (Visit 1)
• Has a diagnosis of FECD at Visit 1
• Meet all other inclusion criteria outlined in the Clinical Study Protocol.
Exclusion Criteria:
• Is a female subject of childbearing potential and any of the following is true:
1. is pregnant or lactating/breastfeeding, or
2. is not surgically sterile, not post-menopausal (no menses for the previous 12
months), or not practicing an effective method of birth control as determined by
the Investigator (eg, oral contraceptives, double barrier methods, hormonal
injectable or implanted contraceptives, tubal ligation, or partner with
vasectomy)
• Meet any other exclusion criteria outlined in the Clinical Study Protocol.
A Phase 1/2 Study of DCC-3116 in Patients With MAPK Pathway Mutant Solid Tumors
This is a Phase 1/2, multicenter, open label, first in human (FIH) study of DCC-3116 as
monotherapy, and in combination with trametinib, binimetinib, or sotorasib in patients with
advanced or metastatic solid tumors with RAS/MAPK pathway mutation. The study consists of 2
parts, a dose-escalation phase, and an expansion phase.
Nataliya Uboha, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04892017
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Inclusion Criteria:
1. Male or female participants ≥18 years of age
2. Dose Escalation Phase (Part 1):
1. Participants must have a pathologically confirmed diagnosis of an advanced or
metastatic solid tumor with a documented RAS, NF1, or RAF mutations. A molecular
pathology report documenting mutational status of RAS, NF1, or RAF must be
available.
2. Progressed despite standard therapies, and received at least 1 prior line of
anticancer therapy.
• Participants with a documented mutation in BRAF V600E or V600K must have
received approved treatments known to provide clinical benefit prior to
study entry.
3. Participants enrolled in the DCC-3116 and sotorasib cohort (Cohort D) must have a
KRAS G12C mutation.
3. Dose Expansion Phase (Part 2):
1. Cohort 1: Patients with Pancreatic Ductal Adenocarcinoma (PDAC).
• Pathologically confirmed PDAC with a documented mutation in KRAS.
• Received only 1 prior line of systemic therapy in the advanced or metastatic
setting.
2. Cohort 2: Patients with Non-Small Cell Lung Cancer (NSCLC)
• Pathologically confirmed NSCLC with a documented mutation in KRAS, NRAS,
NF1, or BRAF.
• Received at least 2 prior lines but no more than 4 prior lines of systemic
therapy in the advanced or metastatic setting.
3. Cohort 3: Patients with Colorectal Cancer (CRC)
• Pathologically confirmed CRC with a documented mutation in KRAS, NRAS, NF1,
or BRAF.
• Received at least 2 prior lines of systemic therapy in the advanced or
metastatic setting.
4. Cohort 4: Patients with Melanoma
• Pathologically confirmed melanoma with a documented mutation in NRAS.
• Received at least 1 but not more than 2 prior lines of systemic therapy in
the advanced or metastatic setting that included T-cell checkpoint
inhibitor-based therapy.
• Have not received prior MEK inhibitor therapy.
5. Cohort 5: Patients with KRAS G12C mutant NSCLC
• Pathologically confirmed NSCLC with a documented mutation in KRAS G12C.
• Received at least 1 prior line but no more than 3 prior lines of systemic
therapy in the advanced or metastatic setting.
• Have not received prior sotorasib or other KRAS G12C inhibitor therapy.
4. Must provide a fresh tumor biopsy from a primary or metastatic cancer lesion that can
be biopsied with acceptable risk as determined by the Investigator, and an archival
tumor tissue sample, if available. If a fresh tumor biopsy is not possible, then an
archival tumor tissue sample must be provided.
5. Eastern Cooperative Oncology Group (ECOG) score of 0 to 2 (Dose Escalation) or 0 to 1
(Dose Expansion) at Screening
6. Adequate organ function and bone marrow function.
7. If a female of childbearing potential must have a negative pregnancy test prior to
enrollment and agree to follow the contraception requirements.
8. Male participants must agree to follow contraception requirements.
9. Must provide signed consent to participate in the study and is willing to comply with
study-specific procedures.
Exclusion Criteria:
1. Must not have received the following within the specified time periods prior to the
first dose of study drug:
1. Prior therapies (anticancer or therapies given for other reasons) that are known
strong or moderate inhibitors or inducers of CYP3A4 or P-gp including certain
herbal medications (eg, St. John's Wort): 14 days or 5× the half-life of the
medication (whichever is longer)
2. All other prior anticancer therapies or any therapy that is investigational for
the participant's condition with a known safety and PK profile: 14 days or 5× the
half-life of the medication (whichever is shorter)
3. Investigational therapies with unknown safety and PK profile: 28 days. If there
is enough data on the investigational therapy to assess the risk for drug.-drug
interactions and late toxicities of prior therapy as low, the Sponsor's Medical
Monitor may approve a shorter washout of 14 days
4. Grapefruit or grapefruit juice: 14 days
2. Have not recovered from all toxicities from prior therapy according to National Cancer
Institute Common Terminology Criteria for Adverse Events (NCI CTCAE).
3. Presence or history of central nervous system (CNS) metastases or leptomeningeal
disease, with some exceptions
4. New York Heart Association Class III or IV heart disease, active ischemia, or any
other uncontrolled cardiac condition such as angina pectoris, clinically significant
cardiac arrhythmia requiring therapy, uncontrolled hypertension, congestive heart
failure, or myocardial infarction within 6 months prior to the first dose of study
drug.
5. Prolongation of the QT interval corrected by Fridericia's formula (QTcF) based on
repeated demonstration of QTcF >450 ms in males or >470 ms in females at screening, or
history of long QT syndrome.
6. Left ventricular ejection fraction (LVEF) <50% at Screening
7. Systemic arterial thrombotic or embolic events
8. Systemic venous thrombotic events
9. Malabsorption syndrome
10. Bone disease that requires ongoing treatment or has required treatment.
11. Major surgery within 4 weeks of the first dose of study drug. All surgical wounds must
be healed and free of infection or dehiscence before the first dose of the study drug.
12. Any other clinically significant comorbidities.
13. For participants receiving DCC-3116 and trametinib combination or DCC-3116 and
binimetinib combination: previous treatment with trametinib or binimetinib that
resulted in treatment discontinuation due to intolerability as a result of an adverse
event (AE) that was considered related to trametinib or binimetinib.
14. For participants receiving DCC-3116 and sotorasib combination in Dose Escalation Part
1: previous treatment with sotorasib that resulted in treatment discontinuation due to
intolerability as a result of an adverse event (AE) that was considered related to
sotorasib.
15. For participants receiving DCC-3116 and sotorasib combination: Use of proton pump
inhibitors (PPIs) and H2 receptor antagonists that cannot be discontinued 3 days prior
to the start of study drug administration.
16. Known allergy or hypersensitivity to any component of the investigational drug
products.
17. Known human immunodeficiency virus unless the following requirements are met:
1. CD4 count >350/µL
2. No AIDS-defining opportunistic infection in the last 12 months
3. Stable anti-retroviral regimen with medications that are not prohibited by the
protocol for at least 4 weeks with HIV viral load less than 400 copies/mL prior
to enrollment.
18. Known active hepatitis B, active hepatitis C infection or if the participant is taking
medications that are prohibited per protocol.
19. If female, the participant is pregnant or lactating.
20. Ongoing participation in an interventional study.
21. For participants receiving DCC-3116 and binimetinib combination: Known Gilbert's
syndrome
Pancreatic Ductal Adenocarcinoma, Non-Small Cell Lung Cancer, Colorectal Cancer, Melanoma, Advanced Solid Tumor, Metastatic Solid Tumor, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Melanoma/Skin cancer, Sarcoma, Uterus
A Study to Investigate the Safety and Tolerability of Ziftomenib in Combination With Venetoclax/Azacitidine, Venetoclax, or 7+3 in Patients With AML
This Phase 1 study will assess the safety, tolerability, and preliminary antileukemic
activity of ziftomenib in combination with venetoclax and azacitidine (ven/aza), ven, and 7+3
for two different molecularly-defined arms, NPM1-m and KMT2A-r.
Kalyan Nadiminti, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT05735184
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Key
Inclusion Criteria:
• Patients must have a documented NPM1 mutation or KMT2A rearrangement and have either
newly diagnosed or relapsed/refractory AML
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Adequate liver, renal, and cardiac function according to protocol defined criteria
• A female of childbearing potential must agree to use adequate contraception from the
time of screening through 180 days following the last dose of study intervention. A
male of childbearing potential must agree to use abstinence or adequate contraception
from the time of screening through 90 days following the last dose of study
intervention
Key
Exclusion Criteria:
• Diagnosis of either acute promyelocytic leukemia or blast chronic myelomonocytic
leukemia
• Known history of BCR-ABL alteration
• Advanced malignant hepatic tumor [for patients receiving ven/aza combination]
• Administration of live attenuated vaccines within 14 days prior to, during, or after
treatment until B-cell recovery
• Active central nervous system (CNS) involvement by AML.
• Clinical signs/symptoms of leukostasis or WBC > 25,000 / microliter. Hydroxyurea
and/or leukapheresis are permitted to meet this criterion
• Not recovered to Grade ≤1 (NCI-CTCAE v5.0) from all nonhematological toxicities except
for alopecia
• Known clinically active human immunodeficiency virus, active hepatitis B or active
hepatitis C infection
• For newly diagnosed cohorts: received prior chemotherapy for leukemia, except
hydroxyurea and/or leukapheresis to control leukocytosis, prior treatment with
all-transretinoic acid for initially suspected acute promyelocytic leukemia, or
non-HMA therapy for prior myelodysplastic syndrome
• For relapsed/refractory cohorts: received chemotherapy, immunotherapy, radiotherapy,
or any ancillary therapy that is considered to be investigational < 14 days prior to
the first dose of ziftomenib or within 5 drug half-lives prior to the first dose of
study drug
• Uncontrolled intercurrent illness including, but not limited to, cardiac illness as
defined in the protocol
• Mean corrected QT interval corrected for heart rate by Fredericia's formula (QTcF)
>480 ms on triplicate ECGs
• Uncontrolled infection
• Women who are pregnant or lactating
• An active malignancy and currently receiving chemotherapy for that malignancy or
disease that is uncontrolled/progressing
Evaluating the Addition of Adjuvant Chemotherapy to Ovarian Function Suppression Plus Endocrine Therapy in Premenopausal Patients With pN0-1, ER-Positive/HER2-Negative Breast Cancer and an Oncotype Recurrence Score Less Than or Equal to 25 (OFSET)
This Phase III Trial will determine whether adjuvant chemotherapy (ACT) added to ovarian
function suppression (OFS) plus endocrine therapy (ET) is superior to OFS plus ET in
improving invasive breast cancer-free survival (IBCFS) among premenopausal, early- stage
breast cancer (EBC) patients with estrogen receptor (ER)-positive, HER2-negative tumors and
21-gene recurrence score (RS) between 16-25 (for pN0 patients) and 0-25 (for pN1 patients).
Malinda West, MD
Female
18 Years to 60 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT05879926
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Inclusion Criteria:
• A patient cannot be considered eligible for this study unless ALL of the following
conditions are met.
• The patient or a legally authorized representative must provide study-specific
informed consent prior to pre-entry and, for patients treated in the U.S.,
authorization permitting release of personal health information.
• Female patients must be greater than or equal to 18 years of age.
• Patients must be premenopausal (evidence of functioning ovaries) at the time of
pre-entry. For study purposes, premenopausal is defined as:
• Age 50 years or under with spontaneous menses within 12 months; or
• Age greater than 50-60 years with spontaneous menses within 12 months plus
follicle-stimulating hormone (FSH) and estradiol levels in the premenopausal
range; or
• Patients with amenorrhea due to IUD or prior uterine ablation must have FSH and
estradiol levels in the premenopausal range; or
• Patients with prior hysterectomy must have FSH and estradiol levels in the
premenopausal range.
• The patient must have an ECOG performance status of less than or equal to 2 (or
Karnofsky greater than or equal to 60%).
• Patients may have ipsilateral or contralateral synchronous breast cancer if the
highest stage tumor meets entry criteria, and the other sites of disease would
not require chemotherapy or HER2-directed therapy.
• Patients may have multicentric or multifocal breast cancer if the highest stage
tumor meets entry criteria, and the other sites of disease would not require
chemotherapy or HER2-directed therapy.
• Patient may have undergone a total mastectomy, skin-sparing mastectomy,
nipple-sparing mastectomy, or a lumpectomy.
• For patients who undergo a lumpectomy, the margins of the resected specimen or
re-excision must be histologically free of invasive tumor and DCIS (ductal
carcinoma in situ) with no ink on tumor as determined by the local pathologist.
If pathologic examination demonstrates tumor at the line of resection, additional
excisions may be performed to obtain clear margins. Positive posterior margin is
allowed if surgeon deems no further resection possible. (Patients with margins
positive for LCIS (lobular carcinoma in situ) are eligible without additional
resection.)
• For patients who undergo mastectomy, the margins must be free of residual gross
tumor. (Patients with microscopic positive margins are eligible if
post-mastectomy RT (radiation therapy) of the chest wall will be administered.)
• Patient must have undergone axillary staging with sentinel node biopsy (SNB),
targeted axillary dissection (TAD), or axillary lymph node dissection (ALND).
• The following staging criteria must be met postoperatively according to AJCC 8th
edition criteria:
• By pathologic evaluation, primary tumor must be pT1-3. (If N0, must be T1c or
higher.)
• By pathologic evaluation, ipsilateral nodes must be pN0 or pN1 (pN1mi, pN1a,
pN1b, pN1c).
• Patients with positive isolated tumor cells (ITCs) in axillary nodes will be
considered N0 for eligibility purposes.
• Patients with micrometastatic nodal involvement (0.2-2 mm) will be considered N1.
• Oncotype DX RS (recurrence score) requirements*:
• If node-negative:
• Oncotype DX RS must be RS 21-25, or
• Oncotype DX RS must be 16-20 and disease must be high clinical risk, defined as:
low histologic grade with primary tumor size greater than 3 cm, intermediate
histologic grade with primary tumor size greater than 2 cm, or high histologic
grade with primary tumor size greater than 1 cm.
• If 1-3 nodes involved:
• Oncotype DX RS must be less than 26.
* Patients with a "Low Risk" or "MP1" MammaPrint (a genomic test that analyzes
the activity of certain genes in early-stage breast cancer) result must have
eligibility assessed with an Oncotype DX RS at pre-entry (see Section 3.1).
Blocks or unstained slides must be sent to the Genomic Health centralized
laboratory for testing at no cost to these patients. If MammaPrint High Risk or
MP2, these patients are not eligible.
• The tumor must be ER and/or PgR-positive (progesterone receptor) by current
ASCO/CAP guidelines based on local testing results. Patients with greater than or
equal to 1% ER and/or PgR staining by IHC will be classified as positive.
• The tumor must be HER2-negative by current ASCO/CAP (American Society of Clinical
Oncology/College of American Pathologists) guidelines based on local testing
results.
• The interval between the last surgery for breast cancer (including re-excision of
margins) and pre-entry must be no more than 16 weeks.
• Short course of endocrine therapy of less than 6 weeks duration before pre-entry
is acceptable either as neoadjuvant or adjuvant therapy. An Oncotype DX RS must
be performed on core biopsy specimen obtained prior to initiation of neoadjuvant
endocrine therapy if received.
• Patients with a prior or concurrent non-breast 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. This would
include prior cancers treated with curative intent.
• HIV-infected patients on effective anti-retroviral therapy with undetectable
viral load within 6 months are eligible for this trial.
• Radiation therapy should be used according to standard guidelines; the intended
radiation therapy should be declared prior to pre-entry.
Exclusion Criteria:
• • Definitive clinical or radiologic evidence of metastatic disease.
• pT4 (pathological state) tumors, including inflammatory breast cancer.
• History of ipsilateral or contralateral invasive breast cancer. (Patients with
synchronous and/or previous DCIS or LCIS are eligible.)
• If prior ipsilateral DCIS was treated with lumpectomy and XRT (ionizing radiation
therapy), a mastectomy must have been performed for the current cancer.
• Life expectancy of less than 10 years due to co-morbid conditions in the opinion
of the investigator.
Known results from most recent lab studies obtained as part of routine care prior to study
entry showing ANY of the following values:
• ANC (absolute neutrophil count) less than 1200/mm3;
• Platelet count less than 100,000/mm3;
• Hemoglobin less than 10 g/dL;
• Total bilirubin greater than ULN (upper limit of normal) for the lab or greater than
1.5 x ULN for patients who have a bilirubin elevation due to Gilbert's disease or
similar syndrome involving slow conjugation of bilirubin;
• AST(aspartate aminotransferase)(SGOT)/ALT (alanine transminase)(SGPT): greater than 3
× institutional ULN;
• Renal function of GFR (glomular filtration rate) less than 30 mL/min/1.73m2.
• Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, patients should be class 2B or better.
• Non-epithelial breast malignancies such as sarcoma or lymphoma.
• Any treatment with radiation therapy, chemotherapy, or biotherapy administered for the
currently diagnosed breast cancer prior to pre-entry. (Patients with prior ET of more
than 6 weeks duration for treatment of this cancer are not eligible.) Prior tamoxifen
given for breast cancer prevention is allowed. Prior AI or GnRH for fertility
preservation is allowed.
• Hormonally based contraceptive measures must be discontinued prior to pre-entry
(including progestin/progesterone IUDs).
• Patients with evidence of chronic hepatitis B virus (HBV) infection are ineligible
unless the HBV viral load is undetectable on suppressive therapy. Patients with a
history of hepatitis C virus (HCV) infection are ineligible unless they have been
treated and cured or have an undetectable HCV viral load if still on active therapy.
• Pregnancy or lactation at the time of pre-entry. (Note: Pregnancy testing according to
institutional standards for women of childbearing potential must be performed within 2
weeks prior to pre-entry.)
• Other conditions that, in the opinion of the investigator, would preclude the patient
from meeting the study requirements or interfere with interpretation of study results.
Testing the Addition of High Dose, Targeted Radiation to the Usual Treatment for Locally-Advanced Inoperable Non-small Cell Lung Cancer
This phase III trial compares the effect of adding stereotactic body radiation therapy (SBRT)
to standard treatment (image guided radiation therapy [IGRT] and chemotherapy followed by
immunotherapy with durvalumab) versus standard treatment alone in treating patients with
non-small cell lung cancer that cannot be treated by surgery (inoperable). SBRT uses special
equipment to position a patient and deliver radiation to tumors with high precision. This
method may kill tumor cells with fewer doses over a shorter period and cause less damage to
normal tissue. IGRT is a type of radiation that uses a computer to create picture of the
tumor, to help guide the radiation beam during therapy, making it more accurate and causing
less damage to healthy tissue. Standard chemotherapy used in this trial consists of
combinations of the following drugs: cisplatin, carboplatin, paclitaxel, pemetrexed, and
etoposide. Cisplatin is in a class of medications known as platinum-containing compounds. It
works by killing, stopping or slowing the growth of tumor cells. Carboplatin is in a class of
medications known as platinum-containing compounds. It works in a way similar to the
anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by
killing, stopping or slowing the growth of tumor cells. Paclitaxel is in a class of
medications called antimicrotubule agents. It works by stopping the growth and spread of
tumor cells. Pemetrexed is in a class of medications called antifolate antineoplastic agents.
It works by blocking the action of a certain substance in the body that may help tumor cells
multiply. Etoposide is in a class of medications known as podophyllotoxin derivatives. It
blocks a certain enzyme needed for cell division and DNA repair and may kill tumor cells.
Immunotherapy with durvalumab, may induce changes in body's immune system and may interfere
with the ability of tumor cells to grow and spread. Adding SBRT to the standard treatment of
IGRT with chemotherapy and immunotherapy may be more effective at treating patients with
inoperable non-small cell lung cancer than giving the standard treatment alone.
Andrew Baschnagel, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05624996
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Inclusion Criteria:
• Pathologically (histologically or cytologically) proven diagnosis of stage II or III
(American Joint Committee on Cancer [AJCC] eighth edition) non-small cell lung cancer
(NSCLC) with known PD-L1 status prior to registration
• Patients must have an identified primary tumor and at least one nodal metastasis
(peribronchial/hilar/intrapulmonary, mediastinal/subcarinal,
supraclavicular/scalene)
• Up to 4 cycles of systemic therapy received prior to registration for the current
study cancer is allowable; any prior chemotherapy for a different cancer is also
permissible
• The patient must be deemed clinically appropriate for curative intent definitive
combined modality therapy, based on the following staging assessments:
• History/physical examination prior to registration;
• Magnetic resonance imaging (MRI) scan of the brain (preferred) or CT scan of the
brain (if available, contrast is preferred for all neuroimaging) prior to
registration;
• CT chest with IV contrast (if contrast is available and unless contraindicated,
such as for abnormal kidney function) prior to registration. PET/CT may be used
if the CT portion is of identical diagnostic quality as achieved in a stand-alone
CT
• No evidence of distant metastases based on FDG PET/CT scan obtain within 60 days of
registration
• Primary tumor =< 7 cm
• Age >= 18
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Hematologic function (e.g. platelets, leukocytes, hemoglobin) amenable, at the
discretion of the treating physician, to allow for treatment with chemotherapy and
concurrent radiation therapy
• Creatinine clearance >= 25 mL/min by the Cockcroft-Gault (C-G) equation
• Subjects with non-malignant pleural effusion are eligible provided the effusion is not
known or demonstrated to be an exudative effusion
• If a pleural effusion is present, the following criteria must be met to exclude
malignant involvement:
• When pleural fluid is visible on both the CT scan and on a chest x-ray, a
pleuracentesis is required to confirm that the pleural fluid is
cytologically negative;
• Effusions that are minimal (i.e., not visible on chest x-ray) that are too
small to safely tap are eligible
• Medical history consistent with the patient being amenable, at the discretion of the
treating physician, to allow for treating with consolidation immunotherapy. Patients
with known EGFR/ALK mutation at the time of registration are eligible, and these
patients can be treated with consolidation durvalumab or chemotherapy at the
discretion of the treating physician
• 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
• Negative pregnancy test =< 14 days prior to registration for participants of
childbearing potential
• The patient or a legally authorized representative must provide study-specific
informed consent prior to study entry and, for patients treated in the United States
(U.S.), authorization permitting release of personal health information
Exclusion Criteria:
• Prior radiotherapy to the region of the study cancer that would result in overlap of
radiation therapy fields that is determined by the treating physician to impede the
treatment of the study malignancy
• Patients without identifiable primary tumor and at least 1 pathologically enlarged
lymph node are not eligible (T3-4N0 or T0N1-3 patients are not eligible). At least 1
radiographically-involved lymph node is required, but pathologic confirmation of
involvement is not mandated
• Centrally located primary tumor < 2 cm from involved nodal disease which would result
in significant overlap of the primary SBRT and nodal radiation fields. Centrally
located is defined as within or touching the zone of the proximal bronchial tree,
which is a volume 2 cm in all directions around the proximal bronchial tree (carina,
right and left main bronchi, right and left upper lobe bronchi, intermedius bronchus,
right middle lobe bronchus, lingular bronchus right and left lower lobe bronchi)
• Participants who are pregnant or unwilling to discontinue nursing
• Participants of childbearing potential (participants who may become pregnant or who
may impregnate a partner) unwilling to use highly effective contraceptives during
therapy and for the Food and Drug Administration (FDA)-labeled contraception timeframe
required after the final dose of the selected chemotherapy regimen, because the
treatment in this study may be significantly teratogenic
Lung, Locally Advanced Lung Non-Small Cell Carcinoma, Stage IIB Lung Cancer AJCC v8, Stage III Lung Cancer AJCC v8
A Study of Alpelisib and Fulvestrant to Treat Endometrial Cancer
This is a 2 stage multi-center study designed to evaluate the efficacy of the combination of
alpelisib and fulvestrant in patients with PIK3CA-mutated ER-positive endometrioid
endometrial cancers by estimating the objective response rate (ORR). Treatment will continue
until either unacceptable toxicity, progression of disease, or investigator/patient request
for withdrawal.
Janelle Sobecki, MD
Female
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05154487
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Inclusion Criteria:
1. Patient must have advanced (FIGO 2014 Stage III or IV), persistent, or recurrent
endometrial carcinoma, which is not likely to be curable by surgery or radiotherapy.
Histologic confirmation of recurrent disease is required. For cases of persistent
disease, histologic confirmation of the primary disease with radiologic evidence of
progression is required.
2. Patients must have endometrioid histology (all grades allowed) based on hysterectomy
or biopsy specimen and have positive expression of ER and oncogenic PIK3CA mutation
per criteria below.
a. PIK3CA mutations considered oncogenic include R88Q, N345K, C420R, E542K, E545X,
Q546X, M1043I, H1047X, or G1049R. The list of oncogenic mutations acceptable for
enrollment may be expanded as further information becomes available.
i. Oncogenic PIK3CA mutations identified on tests performed by the labs listed on
https://ecog-acrin.org/nci-match-eay131-designated-labs will be considered confirmed
for the purposes of this study ii. Oncogenic PIK3CA mutations identified by other
tests will need to be confirmed by the study prior to enrollment b. Estrogen receptor
(ER) status will be considered positive if ≥1% of tumor cells demonstrate positive
nuclear staining by immunohistochemistry. Pathology report documenting ER status must
be provided at enrollment.
Sites are required to report results of previous MMR and/or MSI status testing in
Medidata Rave if available.
3. All patients must have measurable disease. Measurable disease is defined by RECIST
version 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 greater than or equal to 10mm when measured by CT, MRI or caliper
measurement by clinical exam; or greater than or equal to 20mm when measured by chest
x-ray. Lymph nodes must be greater than or equal to 15mm in short axis when measured
by CT or MRI.
Patients must have at least one "target lesion" to be used to assess response on this
protocol as defined by RECIST 1.1. Tumors within a previously irradiated field will be
designated as "non-target" lesions unless progression is documented or a biopsy is
obtained to confirm persistence at least 90 days following completion of radiation
therapy.
4. Prior chemotherapy in the adjuvant setting for Stage I, II, or III is permitted. Prior
chemoradiotherapy for a pelvic recurrence is permitted.
Note: No prior chemotherapy in the setting of Stage IV disease is permitted unless the
patient was without evidence of disease at the completion of chemotherapy and had a
least six months of progression-free survival since the completion of chemotherapy.
Regardless of circumstances, no more than one prior chemotherapy regimen (including
chemo-radiotherapy) is permitted.
Patients who received prior chemotherapy must have recovered (Common Terminology
Criteria for Adverse Events [CTCAE] Grade ≤1) from the acute effects of chemotherapy
except for residual alopecia or Grade 2 peripheral neuropathy prior to enrollment. A
washout period of at least 21 days is required between last chemotherapy dose and
initiation of therapy.
Patients who received radiotherapy must have completed and fully recovered from the
acute effects of radiotherapy. A washout period of at least 14 days is required
between end of radiotherapy and initiation of therapy.
5. Patient must be able to swallow oral medications.
6. Patient must have an ECOG performance status of 0 to 1.
7. Patients must have adequate glucose control as defined by the following (both criteria
must be met):
• Fasting blood glucose (FBG) ≤140/dL (7.7mmol/L) AND
• Hemoglobin A1c (HbA1c) ≤6.4%
8. Patients must have adequate organ and marrow function as defined below NOTE:
Institutional/laboratory upper limit of normal = ULN Institutional/laboratory lower
limit of normal = LLN
Bone marrow function:
• Absolute neutrophil count (ANC) greater than or equal to 1500/mcl
• Platelets greater than or equal to 100,000 cells/mcl
• Hemoglobin greater than or equal to 8 g/dL (Patients may receive erythrocyte
transfusions to achieve this hemoglobin level at the discretion of the
investigator. Initial treatment must not begin earlier than the day after
erythrocyte transfusion).
Renal function:
• Creatinine Clearance ≥ 35 mL/min using Cockcroft-Gault formula
Pancreatic function:
• Fasting Serum amylase ≤ 2 × ULN
• Fasting Serum lipase ≤ ULN
Hepatic function:
• Bilirubin less than or equal to 1.5 x ULN (Patients with Gilbert's syndrome with
a total bilirubin ≤2 times ULN and direct bilirubin within normal limits are
permitted).
• ALT (alanine aminotransferase) and AST (aspartate aminotransferase) less than or
equal to 3 x ULN
• Alkaline phosphatase less than or equal to 2.5 x ULN
• Albumin greater than or equal to 2.8 g/dL
9. Patients must have signed an approved informed consent and authorization permitting
release of personal health information.
10. Patients must be at least 18 years of age.
11. Patients of childbearing potential must have a negative serum pregnancy test prior to
the study entry and be practicing a highly effective form of contraception during the
study treatment and for 8 weeks after stopping the treatment.
Highly effective contraception methods include combination of any of the following (oral,
injected, or implanted hormonal contraceptives are prohibited:
• Placement of an intrauterine device (IUD) or intrauterine system (IUS);
• Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault
caps) with spermicidal foam/gel/film/cream/vaginal suppository;
• Total abstinence or;
• Male/female sterilization. Women are considered post-menopausal and not of
child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea
with an appropriate clinical profile (e.g. age appropriate, history of vasomotor
symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy)
or tubal ligation at least six weeks prior to randomization. In the case of
oophorectomy alone, only when the reproductive status of the woman has been confirmed
by follow up hormone level assessment is she considered not of child-bearing
potential.
Exclusion Criteria:
1. Patients who have previously received any PIK3CA, PI3K, mTOR, or AKT inhibitor.
2. Patients with clear cell, serous, carcinosarcoma, mixed histology endometrial cancers,
or uterine sarcomas.
3. Known intolerance or hypersensitivity to alpelisib or fulvestrant, or any of their
excipients.
4. Patients who have previously received hormonal therapy for endometrial cancer.
5. Participant has had major surgery within 14 days prior to study treatment start and/or
has not recovered from major side effects.
6. Participant with an established diagnosis of diabetes mellitus type I or uncontrolled
type II (based on fasting blood glucose [FBG] and HemoglobinA1c [HbA1c], see INCLUSION
CRITERION 7)
7. Patients with concomitant invasive malignancy or a history of other invasive
malignancies, with the exception of non-melanoma skin cancer, are excluded if there is
any evidence of other malignancy being present within the past five years. Patients
are also excluded if their previous cancer treatment contraindicates this protocol.
8. Patients with active bacterial infection (requiring intravenous [IV] antibiotics at
time of initiating study treatment, fungal infection, or detectable viral infection
(such as known human immunodeficiency virus (HIV) positivity or with known active
hepatitis B or C [for example, hepatitis B surface antigen positive]). Screening is
not required for enrollment.
9. Patients with a serious pre-existing medical condition(s) that would preclude
participation in this study (for example: interstitial lung disease or pneumonitis,
severe dyspnea at rest or requiring oxygen therapy, severe renal impairment (i.e.
estimated creatinine clearance <30ml/min), history of major surgical resection
involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative
colitis or pre-existing chronic condition resulting in baseline grade 2 or higher
diarrhea).
10. Patients with a known history of cardiac disease. This includes:
• Uncontrolled hypertension, defined as systolic greater than 150mm Hg or diastolic
greater than 90mm Hg despite antihypertensive medications
• Myocardial infarction, unstable angina, symptomatic pericarditis, or coronary
artery bypass graft (CABG) within 6 months prior to registration.
• New York Heart Association (NYHA) Class II or greater congestive heart failure.
• History of clinically significant cardiac arrhythmias (i.e. ventricular
tachycardia or ventricular fibrillation, complete left bundle branch block, high
grade AV block (e.g. bifascicular block, Mobitz type II and third degree AV block
without pacemaker in place) or serious cardiac arrhythmia requiring medication.
This does not include asymptomatic atrial fibrillation with controlled
ventricular rate.
• Long QT syndrome, family history of idiopathic sudden death or congenital long QT
syndrome, or Fridericia QT correction formula (QTcF) > 470 msec at screening.
• Cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) within 6
months prior to the first date of study therapy.
• Syncope of cardiovascular etiology,
• Sudden cardiac arrest.
11. Participant is currently receiving any of the following medications and cannot be
discontinued 7 days prior to the start of the treatment:
• Strong CYP3A4 inducers
• Inhibitors of BCRP.
12. Patients who are pregnant or breast-feeding.
13. Patients with known central nervous system metastases which was not previously treated
and not fulfilling the following 3 criteria to be eligible for the study:
• Completed prior therapy (including radiation and/or surgery) for CNS metastases ≥
28 days prior to the start of study entry and
• CNS tumor is clinically stable at the time of screening and
• Participant is not receiving steroids and/or enzyme inducing anti-epileptic
medications for brain metastases.
14. Patients with an impairment of gastrointestinal function or gastrointestinal disease
that may significantly alter the absorption of the study drugs (i.e. ulcerative
disease; uncontrolled nausea, vomiting and/or diarrhea; malabsorption syndrome;
clinical signs and symptoms of gastrointestinal obstruction; and/or patients who
require parenteral hydration and/or nutrition).
15. Patients who plan to receive live attenuated vaccines within 1 week of start of
alpelisib and during the study. Patients should also avoid close contact with others
who have received live attenuated vaccines. Examples of live attenuated vaccines
include intranasal influenza, measles, mumps, rubella, oral polio, BCG< yellow fever,
varicella, and TY21a typhoid vaccines.
16. Patients with active bleeding or pathologic conditions that carry high risk of
bleeding such as known bleeding disorder or coagulopathy.
17. Patients who are currently part of or have participated in any clinical investigation
with an investigational drug within 30 days prior to dosing, or within 5 half-lives of
the investigational product, whichever is longer.
18. Patient is not able to understand and to comply with study instructions and
requirements, including oral administration of study treatment.
Endometroid Endometrial Cancer, Corpus Uteri, Uterus
A Study to Characterize the Safety, Tolerability, and Preliminary Efficacy of CFT1946 as Monotherapy and in Combination With Trametinib in Subjects With BRAF V600 Mutant Solid Tumors
The purpose of this study is to evaluate the safety and tolerability of CFT1946 as well as to
determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of
CFT1946 as monotherapy (Arm A) and in combination with trametinib (CFT1946 + trametinib; Arm
B).
Vincent Ma, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT05668585
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Inclusion Criteria:
1. Subject (or legally authorized representative, where applicable) is willing and able
to provide signed informed consent and can follow protocol requirements
2. Subject is ≥18 years of age at time of informed consent
3. Eastern Cooperative Oncology Group performance status of 0 or 1
4. Subject has documented evidence of a BRAF V600 mutation obtained from tumor tissue or
liquid biopsy: (other protocol conditions may apply)
5. Subject must have received ≥1 prior line of SoC therapy for their unresectable locally
advanced or metastatic disease with disease progression on or after last prior
treatment. Prior regimens for these subjects vary by indication and investigational
arm, but must have included the following:
1. Melanoma or NSCLC (Phase 1 and Phase 2 Arms A1 and B1): Prior receipt of a BRAF
inhibitor and an immune checkpoint inhibitor (any sequence or combination). Prior
(neo)adjuvant immunotherapy may be acceptable.
2. CRC: Receipt of a systemic chemotherapy-based regimen per SoC for unresectable
locally advanced or metastatic disease, and previous treatment with BRAF
inhibitor in combination with an EGFR monoclonal antibody. Subjects with
documented MSI-H or dMMR CRC must have received prior immunotherapy. Subjects
with MSS disease must have received at least 2 prior treatments. Subjects who
received neo(adjuvant) chemotherapy regimens may be eligible.
3. ATC: Subjects must have received SoC therapy options including BRAF inhibitor if
available and of benefit to the subject
4. Other BRAF V600 mutant solid tumors (non-CNS): Subjects must have received SoC
therapy options per their Investigator's best judgment, including BRAF inhibitor
if available and of benefit to the subject
6. Subject has measurable disease per RECIST v1.1
7. Adequate bone marrow, liver, renal, and cardiac function
8. A female subject may be eligible if not pregnant, planning a pregnancy, not breast
feeding, a women of non-child bearing potential or a WOCBP willing to comply with
protocol conditions relating to the use contraception, ova or blood donation and
pregnancy testing prior to the first dose
9. A male subject must agree to comply with protocol conditions relating to the use of
contraception, sperm and blood donation
10. Subject can safely swallow a tablet or pill
Other protocol defined exclusion criteria may apply
Exclusion Criteria:
1. Subject has had major surgery within 21 days prior to the planned first dose. Minor
surgery is permitted within 21 days prior to enrollment
2. Subject with CNS involvement (primary tumor or metastatic disease), except if
clinically stable, have no evidence of new or enlarging brain metastases and are on
stable or tapering doses of steroids for at least 7 days prior to first dose. Subjects
with untreated brain metastases may be eligible to enter without prior radiation
therapy.
3. Subject with known malignancy other than trial indication that is progressing or has
required treatment within the past 3 years, except for conditions that have undergone
potentially curative therapy
4. Subject with history of thromboembolic or cerebrovascular events ≤6 months as defined
in the protocol
5. Subject with impaired cardiac function or clinically significant cardiac disease, as
defined in the protocol
6. Subject with history of uncontrolled diabetes mellitus (only for subjects who will
receive CFT1946 + trametinib)
7. Subject with history or current evidence of retinal vein occlusion (RVO),
chorioretinopathy, or current risk factors for RVO (only for subjects who will receive
CFT1946 + trametinib)
8. Subject has received live, attenuated vaccine within 28 days prior to first dose
administration
9. Subject has history of pneumonitis or interstitial lung disease
10. Subject has history of uveitis
11. Subject has known human immunodeficiency virus (HIV) infection (with exceptions)
12. Subject has history of or known HBV or active HCV infection
13. Subject has concurrent administration of strong CYP3A4/5 inhibitors and inducers,
including any herbal medications/supplements
14. Subject has presence of Grade ≥2 toxicity due to prior cancer therapy, excepting
alopecia and hypothyroidism requiring thyroid replacement therapy
15. Subject has initiation or receipt of the following ≤7 days prior to first dose
administration: Hematopoietic colony-stimulating growth factors, transfusion of packed
red blood cells (pRBC), and transfusion of platelets
16. Subject is pregnant, breastfeeding, or expecting to conceive or father children any
time during the study
Other protocol defined exclusion criteria may apply
Solid Tumors, Melanoma, NSCLC, CRC, ATC, Colon, Rectum, Lung, Melanoma, Skin, Thyroid, Colon and Rectum, Melanoma/Skin cancer
A Study to Evaluate the Safety and Efficacy of K-321 Eye Drops After Descemetorhexis in Participants With Fuchs Endothelial Corneal Dystrophy (FECD)
A study to assess the safety and efficacy of K-321 in participants with FECD after
descemetorhexis.
Evan Warner
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05795699
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Inclusion Criteria:
• Is at least 18 years old at the screening visit (Visit 1)
• Has a diagnosis of FECD at Visit 1
• Meets all other inclusion criteria outlined in clinical study protocol
Exclusion Criteria:
• Is a female patient of childbearing potential and any of the following is true:
1. is pregnant or lactating/breastfeeding, or
2. is not surgically sterile, not post-menopausal (no menses for the previous 12
months), or not practicing an effective method of birth control as determined by
the Investigator (eg, oral contraceptives, double barrier methods, hormonal
injectable or implanted contraceptives, tubal ligation, or partner with
vasectomy)
• Has a study eye with a history of cataract surgery within 90 days of Visit 1
• Meet any other exclusion criteria outlined in clinical study protocol
Testing the Combination of New Anti-cancer Drug Peposertib With Avelumab and Radiation Therapy for Advanced/Metastatic Solid Tumors and Hepatobiliary Malignancies
This phase I/II trial studies the best dose and side effects of peposertib and to see how
well it works with avelumab and hypofractionated radiation therapy in treating patients with
solid tumors and hepatobiliary malignancies that have spread to other places in the body
(advanced/metastatic). Peposertib may stop the growth of tumor cells by blocking some of the
enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as avelumab,
may help the body's immune system attack the cancer, and may interfere with the ability of
tumor cells to grow and spread. Hypofractionated radiation therapy delivers higher doses of
radiation therapy over a shorter period of time and may kill more tumor cells and have fewer
side effects. Giving peposertib in combination with avelumab and hypofractionated radiation
therapy may work better than other standard chemotherapy, hormonal, targeted, or
immunotherapy medicines available in treating patients with solid tumors and hepatobiliary
malignancies.
Jeremy Kratz, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04068194
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Inclusion Criteria:
• PHASE 1: Patients must have a histologically confirmed metastatic or locally advanced
unresectable solid tumor that has progressed on or after available standard of care
therapy or for which no acceptable standard of care therapy exists, or in which the
patient declines standard of care therapy (each patient that declines standard of care
therapy will be documented in the case report form)
• PHASE 2: Patients must have a histologically confirmed metastatic or locally advanced
unresectable cholangiocarcinoma/gallbladder carcinoma that has progressed on at least
1 prior standard of care therapy or for which no acceptable standard of care therapy
exists, or in which the patient declines standard of care therapy (each patient that
declines standard of care therapy will be documented in the case report form)
• Age >= 18 years
• Because no dosing or adverse event data are currently available on the use of
M3814 in combination with avelumab in patients < 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Patients with at least 1 index lesion to irradiate for whom palliative radiation
treatment is indicated (including but not limited to pain and/or symptom control,
prevention of disease -related complications, and preservation of organ function).
Lung and liver lesions are preferred, though alternate lesions may be considered after
discussion with trial principal investigator (PI). Up to 2 lesions may be considered
for irradiation provided at least 1 lesion will receive the study treatment of total
of 60 Gy and all prescribed irradiation will be completed within the radiation window
• Patients with at least 1 Response Evaluation Criteria in Solid Tumors (RECIST)
measurable lesion (to be unirradiated) (defined as those accurately measured in at
least one dimension, with the longest diameter to be recorded for non-nodal lesions
and the shortest diameter for nodal lesions). Measurable is defined as at least 10 mm
in longest diameter for solid tumors, at least 15 mm in shortest diameter for lymph
nodes
• Patients must be willing to undergo fresh biopsies at baseline (as opposed to using
archival tissue), in the event their baseline tissue was obtained > 12 months prior to
study consent and/or they are randomized to the gamma H2AX pNBS1 multiplex IFA assay
• Absolute neutrophil count (ANC) >= 1,500/mcL
• Platelet count >= 100,000/mcL
• Hemoglobin >= 9.0 g/dL
• Serum creatinine =< 1.5 x upper limit of normal (ULN) OR calculated serum creatinine
clearance (glomerular filtration rate [GFR] can be used in place of creatinine or
creatinine clearance) >= 60 mL/min for participants with creatinine levels > 1.5 x
institutional ULN
• Calculate serum creatinine clearance using the standard Cockcroft-Gault formula
• Serum total bilirubin =< 1.5 x ULN or direct bilirubin =< ULN for participants with
total bilirubin > 1.5 x ULN
• Patients with known Gilbert disease with serum bilirubin level =< 3 x ULN are
eligible
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x
ULN or =< 5.0 x ULN for patients with hepatobiliary tumors/liver metastases
• Albumin >= 2.8 g/L
• International normalized ratio (INR) or prothrombin time (PT) or activated partial
thromboplastin time (aPTT) =< 1.5 x ULN
• This applies only to patients not receiving therapeutic anticoagulation; patients
receiving therapeutic anticoagulation should be on a stable dose
• Participants must have the ability to swallow and retain oral medication and not have
any clinically significant gastrointestinal abnormalities that might alter absorption
• Female patients of childbearing potential must have a negative urine or serum
pregnancy test within 72 hours prior to receiving the first dose of study medication.
If the urine test is positive or cannot be confirmed as negative, a serum pregnancy
test will be required. The effects of M3814 and avelumab on the developing human fetus
are unknown and there is the potential for teratogenic or abortifacient effects. For
this reason, women and men of child-bearing potential must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to study
entry, for the duration of study treatment, and for 6 months after completion of M3814
and avelumab administration. Should a woman become pregnant or suspect she is pregnant
while she or her partner is participating in this study, she should inform her
treating physician immediately. Because there is an unknown but potential risk for
adverse events in nursing infants secondary to treatment of the mother with M3814 and
avelumab, breastfeeding should be discontinued if the mother is treated with M3814 and
avelumab
• Ability to understand and the willingness to sign a written informed consent document.
Participants with impaired decision-making capacity (IDMC) who have a close caregiver
or legally authorized representative (LAR) and/or family member available will also be
eligible
Exclusion Criteria:
• PHASE I: Patients who have received prior anti-CTLA-4, anti-PD-1, anti-PD-L1 or other
immune checkpoint inhibitor therapeutic antibodies or pathway-targeting agents
• PHASE II: Patients who have received prior anti-CTLA-4, anti-PD-1, anti-PD-L1 or other
immune checkpoint inhibitor therapeutic antibodies or pathway-targeting agents with
the following exceptions:
• Patients who have only received previous durvalumab (anti-PD-L1) in combination
with gemcitabine +/- cisplatin as part of first line therapy (TOPAZ-1 regimen)
are eligible
• Patients who have only received previous pembrolizumab (anti-PD-1) in combination
with gemcitabine +/- cisplatin as part of first line therapy (KEYNOTE-966
regimen) are eligible
• Patients who have had chemotherapy, definitive radiation, biological cancer therapy,
or investigational agent/device within 21 days of first planned dose of study therapy
(within 14 days for palliative radiation). Previously irradiated lesions may be
re-irradiated provided there is disease progression in the irradiated lesion and the
prescribed radiation dosage can safely be re- administered
• Patients who have not recovered from adverse events due to prior anti-cancer therapy
(i.e., have residual toxicities > Common Terminology Criteria for Adverse Events
[CTCAE] grade 1) with the exception of alopecia
• Patients with untreated/uncontrolled central nervous system (CNS)/leptomeningeal
disease. Patients with asymptomatic, treated CNS disease are eligible if the treating
physician determines that immediate CNS specific treatment is not required and is
unlikely to be required during the first cycle of therapy and the following criteria
are met:
• Radiographic demonstration of clinical stability upon the completion of
CNS-directed therapy and no evidence of interim progression between the
completion of CNS-directed therapy and the screening radiographic study done >= 4
weeks from completion of radiotherapy and >= 2 weeks from discontinuation of
corticosteroids
• No stereotactic radiation or whole-brain radiation within 28 days prior to
randomization
• Patients with active autoimmune disease requiring systemic corticosteroids greater
than the equivalent of prednisone 10 mg daily including but not limited to: systemic
lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, colitis,
vascular thrombosis associated with antiphospholipid syndrome, Wegener's
granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple
sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis, with the
following exceptions:
• Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid
replacement hormone are eligible
• Patients with controlled type 1 diabetes mellitus on a stable insulin regimen are
eligible
• Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with
dermatologic manifestations only who require only low potency topical steroids
(e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%,
desonide 0.05%, alclometasone dipropionate 0.05%) are eligible
• Patients receiving treatment with systemic immunosuppressive medications (including,
but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate,
thalidomide, and anti-tumor necrosis factor [TNF] agents) within 6 weeks must
discontinue these medications prior to starting M3814 and avelumab on day 7, with the
exception of:
• Patients with active autoimmune disease managed with systemic corticosteroids
less than the equivalent of prednisone 10 mg daily
• Patients who have received acute, low dose, systemic immunosuppressant
medications (e.g., a one-time dose of dexamethasone for nausea)
• The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone)
for patients with orthostatic hypotension and adrenocortical insufficiency
• Patients who have undergone prior solid organ or bone marrow transplant with the
exception of patients with prior renal transplant for whom dialysis may be employed in
the event of graft rejection
• Patients with uncontrolled intercurrent illness (e.g., including but not limited to
uncontrolled hypertension [HTN] [systolic blood pressure (BP) > 150, diastolic BP >
100], symptomatic congestive heart failure [CHF], unstable angina pectoris, ischemic
myocardial infarction [MI] within 6 months, cardiac arrhythmia, recent transient
ischemic attack [TIA or cerebrovascular accident (CVA)]) within 6 months
• Patients with serious active infection (e.g. requiring hospitalization and/or
intravenous [IV] antibiotics) within 4 weeks prior to starting M3814 and avelumab, or
signs/symptoms of infection or receiving oral or IV antibiotics for the treatment of
active systemic infection within 2 weeks prior to starting M3814 and avelumab.
Patients receiving prophylactic antibiotics are eligible
• Patients with known chronic hepatitis B virus (HBV) infection must have an
undetectable viral load on suppressive therapy if indicated. Patients with known
chronic hepatitis C (HCV) infection must have been treated and cured. Patients who are
currently on curative treatment are eligible if they have an undetectable HCV viral
load
• Patients with known human immunodeficiency virus (HIV) are allowed on study provided
they have:
• A stable regimen of highly active anti-retroviral therapy (HAART)
• No requirement for concurrent antibiotics or antifungal agents for the prevention
of opportunistic infection
• A CD4 count above 250 cells/mcL
• An undetectable HIV viral load on standard polymerase chain reaction (PCR)-based
testing
• Patients with history of idiopathic pulmonary fibrosis, pneumonitis (including drug
induced), organizing pneumonia (e.g., bronchiolitis obliterans, cryptogenic organizing
pneumonia), or evidence of active pneumonitis on screening chest computed tomography
(CT) scan
• Patients with known concurrent malignancy that is expected to require active treatment
within two years, or may interfere with the interpretation of the efficacy and safety
outcomes of this study in the opinion of the treating investigator. Superficial
bladder cancer, nonmelanoma skin cancers, and low-grade prostate cancer not requiring
cytotoxic therapy should not exclude participation in this trial. Patients with
chronic lymphocytic leukemia (CLL) may be enrolled if they do not require active
chemotherapy and their hematologic, renal and hepatic function meets criteria
previously mentioned
• Patients with psychiatric illness/social situations that would limit compliance with
study requirements
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to M3814 or avelumab
• Patients unable to discontinue medications or substances that are potent inhibitors,
inducers or sensitive substrates of CYP3A4/5 or CYP2C19 prior to starting M3814 and
avelumab are ineligible. Medications or substances that are strong inhibitors of
CYP3A4/5 or CYP2C19 must be discontinued at least 1 week prior to first M3814 dose.
Strong inducers of CYP3A4/5 or CYP2C19 must be stopped at least 3 weeks prior to the
first dose. Drugs mainly metabolized by CYP3A with a narrow therapeutic index as
judged by the investigator must stop at least 1 day prior to first M3814 dose. Because
the lists of these agents are constantly changing, it is important to regularly
consult a frequently-updated medical reference. As part of the enrollment/informed
consent procedures, the patient will be counseled on the risk of interactions with
other agents, and what to do if new medications need to be prescribed or if the
patient is considering a new over-the-counter medicine or herbal product. The primary
elimination mechanism of avelumab is proteolytic degradation, thus there are no
contraindicated medications with respect to avelumab
• Patients who cannot discontinue concomitant proton-pump inhibitors (PPIs) prior to
starting M3814 and avelumab. These must be discontinued >= 5 days prior to starting
M3814 and avelumab. Patients do not need to discontinue calcium carbonate. H2 blockers
are allowed provided they are taken at least 2 hours after M3814 dose
• Patients receiving sorivudine or any chemically related analogues (such as brivudine)
and not able to discontinue prior to starting M3814 and avelumab are excluded
• Pregnant and lactating women are excluded from this study because M3814 and avelumab
are agents with the potential for teratogenic or abortifacient effects. Because there
is an unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with M3814 and avelumab, breastfeeding should be discontinued
if the mother is treated with M3814 and avelumab
• Patients who have received live vaccination within 30 days before starting M3814 and
avelumab
Cholangiocarcinoma, Gallbladder Carcinoma, Malignant Solid Neoplasm, Stage III Gallbladder Cancer AJCC v8, Stage III Hilar Cholangiocarcinoma AJCC v8, Stage III Intrahepatic Cholangiocarcinoma AJCC v8, Stage IV Gallbladder Cancer AJCC v8, Stage IV Hilar Cholangiocarcinoma AJCC v8, Stage IV Intrahepatic Cholangiocarcinoma AJCC v8, Liver, Other Digestive Organ, Gastrointestinal cancers, other
Outcomes and Cosmesis With Whole Breast Irradiation and Boost
This study is being done to evaluate cosmetic, patient-reported outcome measures (PROMs), and
toxicities for women undergoing ultra-short whole breast irradiation (WBI) therapy with
simultaneous integrated boost (SIB). 50 participants will be on study for up to 60 months.
Jessica Schuster, MD
Female
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT06295744
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Inclusion Criteria:
• Ability to understand and the willingness to sign a written informed consent document
• Histologically confirmed early stage (stage T1-T2) invasive carcinoma of the breast or
DCIS
• Breast conserving surgery with negative margins and negative nodes (surgical axillary
staging not mandatory), stage N0 or Nx
• Treatment plan should include breast conserving surgery and adjuvant whole breast
irradiation (WBI) therapy delivered with 3D-CRT or IMRT techniques
• Treatment plan includes breast tumor bed boost
• Willingness to comply with all study procedures and be available for the duration of
the study
Exclusion Criteria:
• Mastectomy of ipsilateral breast
• Lack of histologic diagnosis
• Histologic involvement of the axillary or regional nodes or metastatic disease
• Accelerated partial breast irradiation treatment plan
• Previous history of non-breast malignancy diagnosed in the past 5 years except for
basal or squamous cell cancer of the skin
• Previous history of chest radiation therapy
• Previous history of ipsilateral breast cancer
• Concurrent cytotoxic chemotherapy
• Active connective tissue disease including scleroderma
• Inability or unwillingness to return for required follow up visit
Comparison of Microglial Activation in Severe Asthma and Healthy Controls (MAIA-SC)
The goal of this clinical trial is to learn about how asthma influences brain function. The
main questions it aims to answer are:
- How airway inflammation in asthma affects the brain; and,
- Whether airway inflammation in asthma is related to symptoms of depression and anxiety
Over the course of 3 visits, participants will:
- Complete questionnaires
- Complete computer tasks
- Undergo allergy skin test and breathing tests
- Give two blood samples
- Give a sputum sample
- Complete brain imaging scans
Researchers will compare results between participants with asthma, and participants who do
not have asthma.
Melissa Rosenkranz, PhD
All
18 Years to 75 Years old
N/A
This study is also accepting healthy volunteers
NCT06299592
Show full eligibility criteria
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Inclusion Criteria:
• Ability to understand and the willingness to sign a written informed consent document
• Individuals with no health concerns that might affect the outcome of the study
• Age 18-75 years of age
• Ability to tolerate a simulated MRI brain scanning session
• In the opinion of the investigator, capable and willing to grant written informed
consent and cooperate with study procedures and requirements
• High-affinity TSPO-binding genotype. Mixed (high/low) binding-affinity genotype may be
included at PIs discretion
• For participants with severe asthma:
• Physician diagnosis of asthma for at least six months prior to screening (can be
determined at the discretion of an asthma/allergy physician member of the study team)
• Severe asthmatics must meet the ATS definition of severe asthma and/or be currently
receiving a GINA 5 therapy (or greater), which may include ongoing use of currently
approved biologic immunomodulators
Exclusion Criteria:
• Current smoker (defined as more than 0.5 pack per week for the past 6 months and any
smoking within two weeks of study procedures) or has a smoking history exceeding 5
pack years within the last 10 years
• Currently receiving immunotherapy
• Use of psychotropic medication that might affect function of neurocircuitry implicated
in our hypotheses (at the discretion of the PI/Co-I)
• Inability to hold medications detailed in the medication hold schedule
• Needle phobia or claustrophobia
• Major health problems such as autoimmune disease, history of carotid stenosis, heart
disease, uncontrolled hypertension, or lung diseases other than asthma, history of
significant arrhythmias, and any of the following in the last 6 months: stroke/TIA,
myocardial infarction, stent placement, or acute coronary syndrome. The listed health
problems are definitively exclusionary, but decisions regarding major health problems
not listed will be based upon the judgment of the investigator
• Use of biologic medication that might affect signaling pathways under investigation
(at the discretion of the PI/Co-I)
• Pre-existing chronic infectious disease
• Scheduled use of non-selective beta-blockers prior to each study visit.
• Use of an investigational drug within 30 days of entering the study. This criterion
will be reviewed on a case by case basis by the PI/Co-I to determine appropriate
washout period. Appropriate wash out period may be greater than 30 days depending on
the half-life of the investigational drug. Participants may be eligible for study
participation after completing the washout period designated by the PI or Co-I
(physician only).
• Any MRI incompatibility as determined by most current MRI screening form
• History of a diagnosed bipolar disorder, schizophrenia, or schizoaffective disorder
• History of serious head trauma or seizure disorder (can be included at the discretion
of the PI or Co-I)
• Unable, in the judgement of the investigator, to comply with directions and/or
tolerate the procedures required for participation in this study
• Pregnant or breast-feeding or has a planned pregnancy during the course of the study
• Any other medical condition or disease that would impact participant safety or data
integrity in the opinion of the PI/CO-I
Asthma, Other, Infections, Immune System & Allergies, Healthy Volunteers
A Prospective, Multi-center, Randomized Controlled Blinded Trial Demonstrating the Safety and Effectiveness of VNS Therapy® System as Adjunctive Therapy Versus a No Stimulation Control in Subjects With Treatment-Resistant Depression (RECOVER)
Objectives of this study are to determine whether active VNS Therapy treatment is superior to
a no stimulation control in producing a reduction in baseline depressive symptom severity,
based on multiple depression scale assessment tools at 12 months from randomization.
Steven Garlow, MD, PhD
All
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT03887715
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Inclusion Criteria:
The patient must be in a major depressive disorder (MDD) episode for ≥ two years or have
had at least four episodes of MDD, including the current episode.
The patient's depressive illness meets a minimum criterion of four prior failed treatments
of adequate dose and duration as measured by a tool designed for this purpose.
The patient is experiencing a major depressive episode (MDE) as measured by a guideline
recommended depression scale assessment tool on two visits, within a 45-day span prior to
implantation of the VNS device.
Patients must maintain a stable medication regimen for at least four weeks before device
implantation.
Exclusion Criteria:
Current or lifetime history of psychotic features in any MDE;
Current or lifetime history of schizophrenia or schizoaffective disorder;
Current or lifetime history of any other psychotic disorder;
Current or lifetime history of rapid cycling bipolar disorder;
Current secondary diagnosis of delirium, dementia, amnesia, or other cognitive disorder;
Current suicidal intent; or
Treatment with another investigational device or investigational drugs.
Treatment Resistant Depression, Bipolar disorder, Major depressive disorder, recurrent, Other
A Clinical Trial to Evaluate Efficacy and Safety of TransCon CNP Compared With Placebo in Infants (0 to <2 Years of Age) With Achondroplasia
This trial is a Phase 2, multicenter, double-blind, randomized (ratio 2:1 TransCon CNP vs.
placebo), placebo-controlled trial, designed to evaluate the safety, tolerability, and
efficacy of 100 μg CNP/kg of Navepegritide (TransCon CNP) administered SC once-weekly for 52
weeks in infants with genetically verified heterozygous ACH, aged 0 to < 2 years at the time
of randomization.
Janet Legare
All
0 Years to 2 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT06079398
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Inclusion Criteria:
• Written, signed informed consent by the parent(s)/caregiver(s) of the participant, and
as required by the institutional review board/human research ethics
committee/independent ethics committee (IRB/HREC/IEC).
• Male or female younger than 2 years of age at the time of randomization; or for open
label sentinel participants, at the time of first administration of IMP.
• Clinical diagnosis of achondroplasia (ACH) with genetic confirmation of heterozygous
genotype present during screening.
• Parent(s)/caregiver(s) willing to follow the protocol and instructions provided,
including being able to administer weekly subcutaneous injections of trial treatment.
• Compliance to daily Vitamin D supplementation for infants aged 14 days to 1 year. All
participants older than 1 year of age with serum 25-hydroxyvitamin D (25OHD) measured
below lower limit of reference range at screening should start daily Vitamin D
supplementation prior to randomization.
• Considered eligible based on the medical history, physical examination, and the
results of vital signs, ECG, imaging, and clinical laboratory tests performed during
the screening period.
Exclusion Criteria:
• Known or suspected hypersensitivity to the investigational product or related products
(trehalose, tris[hydroxymethyl]aminomethane, succinate, and polyethylene glycol
[PEG]).
• Genetic confirmation of ACH homozygous genotype.
• Premature birth with gestational age < 32 weeks.
• Premature birth with gestational age 32 to 37 weeks, unless time from birth is > 6
months at the time of screening and the child is in good nutritional status, defined
as gain in body weight expected for age and diagnosis of ACH, as determined by the
Investigator and confirmed with the Medical Monitor.
• Anticipated, as assessed by Investigator and confirmed with Medical Monitor, to
undergo surgical intervention during trial participation, including cervicomedullary
decompression. Evaluation of immediate risk of requiring cervicomedullary
decompression surgery will rely on the following assessments:
• Physical examination (e.g., neurologic findings of clonus, opisthotonus,
exaggerated reflexes, dilated facial veins)
• Evidence of uncontrolled sleep apnea as confirmed by local standard of care
assessment (e.g. polysomnography or simple sleep test) performed within 6 months
prior to screening.
• MRI performed at screening indicating presence of severe cervicomedullary
compression (CMC) or spinal cord damage. Presence of abnormal MRI T2 signal
intensity at and immediately above and below the cervicomedullary junction should
be considered high risk for requiring surgery and the participant is not eligible
for trial participation.
Common surgeries, such as insertion of grommets, adenoidectomy, tonsillectomy, or
myringotomy tube placement are permitted during trial participation.
• Have a growth disorder or medical condition, other than ACH, resulting in short
stature or abnormal growth as determined by the Investigator and confirmed with the
Medical Monitor.
• Have received any dose of prescription medications and/or investigational medicinal
product or device intended to affect stature, growth, or body proportionality
(including human growth hormone or vosoritide) at any time.
• Requires or anticipated to require chronic (> 4 weeks) or repeated treatment (more
than twice/year) with oral corticosteroids, or high-dose inhaled corticosteroids
during trial participation.
• History or presence of injury or disease of the growth plate(s), other than ACH,
affecting growth potential of long bones, including Salter-Harris fracture and recent
bone-related surgery, as determined by Investigator and confirmed with the Medical
Monitor.
• Have a clinically significant finding indicating abnormal cardiac function, including
but not limited to:
• Repaired or unrepaired coarctation.
• Moderate or greater complexity congenital heart disease including tetralogy of
Fallot, atrioventricular septal defects, truncus arteriosus, total anomalous
pulmonary venous return, double outlet right ventricle, or single ventricle heart
disease.
• QTcF ≥ 450 msec on screening 12-lead ECG.
• History or presence of a condition impacting hemodynamic stability (such as autonomic
dysfunction and orthostatic intolerance).
• History or presence of the following:
• Chronic anemia.
• Chronic renal insufficiency.
• Chronic or recurrent illness that can affect hydration or volume status,
including conditions associated with decreased nutritional intake or increased
volume loss.
• History or presence of malignant disease.
• Any disease or condition that, in the opinion of the Investigator, may make the
participant unlikely to fully complete the trial, not adhering to trial procedures,
may confound interpretation of trial results, or may present undue risk from receiving
trial treatment. This could include family situations, comorbid conditions, or
medications that might impact safety or be considered confounding.
Testing the Anti-cancer Drug Erdafitinib for Brain Cancers That Have Returned or Progressed Following Treatment
This phase II trial tests how well erdafitinib works in controlling IDH-wild type (WT)
gliomas with FGFR-TACC gene fusion that have returned or that have grown, spread, or gotten
worse (progressed). Erdafitinib is in a class of medications called kinase inhibitors. It
works by blocking the action of an abnormal FGFR protein that signals tumor cells to
multiply. This may help keep tumor cells from growing and may kill them. Giving erdafitinib
may help to slow the growth of or to shrink tumor cells in patients with recurrent or
progressive IDH-wild type gliomas with FGFR-TACC gene fusion.
Ankush Bhatia, M.D.
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05859334
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Inclusion Criteria:
• Patient must be >= 18 years of age
• Patient must have histologically confirmed IDH-WT gliomas (grade 2-4) as per World
Health Organization (WHO) 2016 or 2021 classification
• Tumor tissue should be positive for FGFR-TACC gene fusion as per any local next
generation sequencing (NGS) (Clinical Laboratory Improvement Act [CLIA]-approved)
assay described in background section
• The disease should be recurrent or progressive glioma after initial anti-tumor
treatment with at least 1 line of treatment including surgical resection, radiation
therapy and/or chemotherapy.
• For patients with WHO grade 3 or 4 glioma and progressive disease < 12 weeks after
completion of chemoradiotherapy, progression can be defined by the following set of
criteria:
• New enhancement outside of the radiation field (beyond the high-dose region or
80% isodose line)
• If there is unequivocal evidence of viable tumor on histopathologic sampling
(e.g., solid tumor areas. i.e., > 70% tumor cell nuclei in areas), high or
progressive increase in Ki-67 proliferation index compared with prior biopsy, or
evidence for histologic progression or increased anaplasia in tumor).
• For patients with WHO grade 3 or 4 glioma and progressive disease >= 12 weeks after
completion of chemoradiotherapy, progression can be defined by the following set of
criteria:
• New contrast-enhancing lesion outside of radiation field on decreasing, stable,
or increasing doses of corticosteroids
• Increase by >= 25% in the sum of the products of perpendicular diameters between
the first post-radiotherapy scan, or a subsequent scan with smaller tumor size,
and the scan at 12 weeks or later on stable or increasing doses of
corticosteroids
• For patients receiving antiangiogenic therapy, significant increase in T2/FLAIR
non-enhancing lesion may also be considered progressive disease. The increased
T2/FLAIR must have occurred with the patient on stable or increasing doses of
corticosteroids compared with baseline scan or best response after initiation of
therapy and not be a result of comorbid events (e.g., effects of radiation
therapy, demyelination, ischemic injury, infection, seizures, postoperative
changes, or other treatment effects).
• For patients with WHO grade 2 glioma progression is defined by any one of the
following:
• Development of new lesions or increase of enhancement (radiological evidence of
malignant transformation)
• A 25% increase of the T2 or FLAIR non-enhancing lesion on stable or increasing
doses of corticosteroids compared with baseline scan or best response after
initiation of therapy, not attributable to radiation effect or to comorbid events
• There must be measurable disease (enhancing or non-enhancing as per Response
Assessment in Neuro-Oncology [RANO] or RANO-low-grade glioma [LGG] criteria), as
evaluated on pre-treatment MRI
• Patient understands the procedures and investigational nature of the study drug and
agrees to comply with study requirements by providing written informed consent
• Patient must have Eastern Cooperative Oncology Group (ECOG) performance status =< 2
(or Karnofsky >= 60%)
• Absolute neutrophil count >= 1000/uL
• Hemoglobin > 8 g/dL (Patients are allowed to be transfused to this level)
• Platelets >= 100 x 10^9/L
• Serum total bilirubin =< 1.5 x upper limit of normal (ULN), unless considered due to
Gilbert's disease or disease involvement following approval by the medical monitor
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =<
3 x institutional ULN
• Creatinine clearance > 30 mL/min (patients with mild or moderate renal impairment)
based on the Cockroft-Gault glomerular filtration rate (GFR) estimation
• Patient must have normal serum phosphate level as per local laboratory parameters.
(Medical management allowed)
• Patient must be recovered from any clinically relevant toxic effects of any prior
surgery, radiotherapy, or chemotherapy treatment with temozolomide
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load
• Patients should be New York Heart Association Functional Classification class 2B or
better
• The effects of erdafitinib on the developing human fetus are unknown. For this reason
and because FGFR inhibitors are known to be teratogenic, women of child-bearing
potential and men must agree to use adequate contraception (hormonal or barrier method
of birth control; abstinence) prior to study entry, for the duration of study
participation, and one month after completion of erdafitinib administration. Should a
woman become pregnant or suspect she is pregnant while she or her partner is
participating in this study, she should inform her treating physician immediately. Men
treated or enrolled on this protocol must also agree to use adequate contraception
prior to the study, for the duration of study participation, and one month after
completion of erdafitinib administration
• Ability to understand and the willingness to sign a written informed consent document.
Legally authorized representatives may sign and give informed consent on behalf of
study participants
Exclusion Criteria:
• Patients who are receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to erdafitinib
• Patients requiring any medications or substances that are moderate CYP2C9 inducers and
strong CYP3A4 inducers are ineligible. Because the lists of these agents are
constantly changing, it is important to regularly consult a frequently-updated medical
reference. As part of the enrollment/informed consent procedures, the patient will be
counseled on the risk of interactions with other agents, and what to do if new
medications need to be prescribed or if the patient is considering a new
over-the-counter medicine or herbal product
• Patients with uncontrolled intercurrent illness
• Pregnant women are excluded from this study because erdafitinib is an FGFR inhibitor
agent with the potential for teratogenic or abortifacient effects. Because there is an
unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with erdafitinib, breastfeeding should be discontinued if the
mother is treated with erdafitinib
• Current central serous retinopathy (CSR) or retinal pigment epithelial detachment of
any grade
• Corrected QT interval (QTc) prolongation as confirmed by electrocardiography (ECG) at
screening (Fridericia; QTc > 480 milliseconds)
• Patients who have previously received FGFR inhibitors
Recurrent Glioblastoma, IDH-Wildtype, Recurrent WHO Grade 2 Glioma, Recurrent WHO Grade 3 Glioma, Brain and Nervous System, Brain/Central Nervous System
A Study Evaluating Atezolizumab and Bevacizumab, With or Without Tiragolumab, in Participants With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma (IMbrave152) (SKYSCRAPER-14)
The purpose of this study is to assess the efficacy and safety of tiragolumab, an anti-TIGIT
monoclonal antibody, when administered in combination with atezolizumab and bevacizumab as
first-line treatment, in participants with unresectable, locally advanced or metastatic
hepatocellular carcinoma (HCC).
Jeremy Kratz, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05904886
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Inclusion Criteria:
• Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by
histology/cytology or clinically by American Association for the Study of Liver
Diseases (AASLD) criteria in cirrhotic participants
• Disease that is not amenable to curative surgical and/or locoregional therapies
• No prior systemic treatment for locally advanced or metastatic and/or unresectable HCC
• Measurable disease according to RECIST v1.1
• ECOG Performance Status of 0 or 1 within 7 days prior to randomization
• Child-Pugh Class A within 7 days prior to randomization
• Adequate hematologic and end-organ function
• Female participants of childbearing potential must be willing to avoid pregnancy
within 5 months after the final dose of atezolizumab, within 6 months after the final
dose of bevacizumab, and within 90 days after the final dose of tiragolumab/placebo
• Male participants with a female partner of childbearing potential or pregnant female
partner must remain abstinent or use a condom during the treatment period and for 6
months after the final dose of bevacizumab and for 90 days after the final dose of
tiragolumab/placebo to avoid exposing the embryo.
Exclusion Criteria:
• Pregnancy or breastfeeding within 5 months after the final dose of atezolizumab,
within 6 months after the final dose of bevacizumab, and within 90 days after the
final dose of tiragolumab/placebo
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies
• Treatment with investigational therapy within 28 days prior to initiation of study
treatment
• Treatment with locoregional therapy to liver within 28 days prior to initiation of
study treatment, or non-recovery from side effects of any such procedure
• Treatment with systemic immunostimulatory agents
• Treatment with systemic immunosuppressive medication
• Untreated or incompletely treated esophageal and/or gastric varices with bleeding or
that are at high risk for bleeding
• A prior bleeding event due to esophageal and/or gastric varices within 6 months prior
to initiation of study treatment
• Active or history of autoimmune disease or immune deficiency
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening
chest computed tomography (CT) scan
• History of malignancy other than HCC within 5 years prior to screening, with the
exception of malignancies with a negligible risk of metastasis or death
• Mixed histology or other subtypes/variants of HCC, including, but not limited to,
known liver adenocarcinoma, fibrolamellar HCC, sarcomatoid HCC, other rare HCC
variant, or mixed cholangiocarcinoma and HCC
• Co-infection with hepatitis B virus (HBV) and hepatitis C virus (HCV)
• Acute Epstein-Barr virus (EBV) infection or known or suspected chronic active EBV
infection
• Symptomatic, untreated, or actively progressing central nervous system (CNS)
metastases.
A Study of Nemtabrutinib (MK-1026) Versus Comparator (Investigator's Choice of Ibrutinib or Acalabrutinib) in First Line (1L) Chronic Lymphocytic Leukemia (CLL)/ Small Lymphocytic Lymphoma (SLL) (MK-1026-011/BELLWAVE-011)
The goal of this study is to evaluate nemtabrutinib compared with investigator's choice of
ibrutinib or acalabrutinib in participants with chronic lymphocytic leukemia (CLL)/small
lymphocytic lymphoma (SLL) who have not received any prior therapy. The primary hypotheses
are that (1) nemtabrutinib is non-inferior to ibrutinib or acalabrutinib with respect to
objective response rate (ORR) per International Workshop on Chronic Lymphocytic Leukemia
(iwCLL) Criteria 2018 by blinded independent central review (BICR) and (2) nemtabrutinib is
superior to ibrutinib or acalabrutinib with respect to progression free survival (PFS) per
iwCLL Criteria 2018 by BICR.
Christopher Fletcher, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT06136559
Show full eligibility criteria
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Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
• Confirmed diagnosis of CLL/SLL and active disease clearly documented to have a need to
initiate therapy.
• Has at least 1 marker of disease burden.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 within 7
days before randomization.
• Has the ability to swallow and retain oral medication.
• Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they
have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have
undetectable HBV deoxyribonucleic acid (DNA) viral load before randomization.
• Participants with history of hepatitis C virus (HCV) infection are eligible if HCV
ribonucleic acid (RNA) viral load is undetectable at screening.
• Participants with human immunodeficiency virus (HIV) who meet ALL eligibility
criteria.
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
• Has an active hepatitis B virus/ hepatitis C virus (HBV/HCV) infection.
• Has gastrointestinal (GI) dysfunction that may affect drug absorption.
• Has diagnosis of Richter Transformation or active central nervous system (CNS)
involvement by CLL/SLL.
• Has had acquired immune deficiency syndrome (AIDS)-defining opportunistic infection in
the past 12 months before screening.
• Has clinically significant cardiovascular disease.
• Has hypersensitivity to nemtabrutinib or contraindication to ibrutinib or
acalabrutinib, or any of the excipients.
• Has history of severe bleeding disorder.
• Has history of second malignancy, unless potentially curative treatment has been
completed with no evidence of malignancy for 2 years.
• Has received any systemic anticancer therapy for CLL/SLL.
• Is currently being treated with p-glycoprotein (P-gp) substrates with a narrow
therapeutic index, cytochrome P450 3A (CYP3A) strong or moderate inducers or CYP3A
strong inhibitors.
• Received prior radiotherapy within 2 weeks of start of study intervention, or
radiation-related toxicities, requiring corticosteroids.
• Received a live or live-attenuated vaccine within 30 days before the first dose of
study intervention. Administration of killed vaccines are allowed.
• Has received an investigational agent or has used an investigational device within 4
weeks before study intervention administration.
• Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in
dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior the first dose of study medication.
• Has active autoimmune disease that has required systemic treatment in the past 2
years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is
allowed.
• Has active infection requiring systemic therapy.
• Participants who have not adequately recovered from major surgery or have ongoing
surgical complications.
Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Non-Hodgkin's Lymphoma, Lymphoma
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