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New treatment option for Recurrent Endometrial Carcinoma
Official title Testing Different Amounts of the Combination of Drugs M1774 and ZEN-3694 for the Treatment of Recurrent Ovarian and Endometrial Cancer
ClinicalTrials.gov ID: NCT05950464
What this study is testing
What is BET Bromodomain Inhibitor ZEN-3694?
BET Bromodomain Inhibitor ZEN-3694 is an investigational medicine, given as an once-daily infusion into a vein, being studied as a potential treatment for recurrent endometrial carcinoma.
Also referred to as BETi ZEN-3694, ZEN 3694.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- This phase Ib trial tests the safety, side effects, and best dose of M1774 when given with ZEN-3694 in treating patients with ovarian and endometrial cancer that has come back (recurrent). M1774 and ZEN-3694 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
- Phase 1: an early, usually small safety study
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older, women only
You may be able to join if
- Patients must have pathologically confirmed:
- PART I: Recurrent clear cell or endometrioid ovarian carcinoma (at least 50% morphology of clear cell and endometrioid required), recurrent clear...
- NOTE: platinum-resistant disease is defined as progression within \< 6 months from completion of platinum-based therapy. The date should be...
- NOTE: Institutional pathology reports must be provided indicating at least 50% endometrioid or clear cell morphology for ovarian cancer.
- NOTE: Patients with recurrent endometrial carcinoma must not be eligible for or decline treatment with curative intent.
You likely can't join if
- Patients who are receiving any other investigational agents.
- Patients who have received prior ATR, ATM, CHK, BET, EZH2, and/or PI3K inhibitors.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ZEN003694 or M1774 used in study.
- Patients taking proton pump inhibitors given decreased solubility of M1774 with increased pH. Proton pump inhibitors must be discontinued 7 days...
- Patients with corrected QT (QTc) over 450msec that does not correct with correction of electrolyte abnormalities or family history of long QT...
- Patients with severe, active co-morbidity defined as follows:
See the full eligibility criteria
Who can join
- Patients must have pathologically confirmed:
- PART I: Recurrent clear cell or endometrioid ovarian carcinoma (at least 50% morphology of clear cell and endometrioid required), recurrent clear cell and low grade endometrioid endometrial carcinoma (The International...
- NOTE: platinum-resistant disease is defined as progression within \< 6 months from completion of platinum-based therapy. The date should be calculated from the last administered dose of platinum therapy
- NOTE: Institutional pathology reports must be provided indicating at least 50% endometrioid or clear cell morphology for ovarian cancer.
- NOTE: Patients with recurrent endometrial carcinoma must not be eligible for or decline treatment with curative intent.
- PART II: Recurrent clear cell or endometrioid ovarian carcinoma (at least 50% tumor morphology of clear cell and endometrioid required). Recurrent clear cell or FIGO Grade 1 endometrioid endometrial carcinoma. Next...
- Age \>= 18
- Eastern Cooperative Oncology Group (ECOG) Performance Status of =\< 2
- Prior Treatment
- 1-3 prior cytotoxic therapies
- NOTE: For platinum-resistant HGSOC (PART 1) may have received up to 3 prior cytotoxic therapies after developing platinum resistant disease.
- people with microsatellite instability- high (MSI-H) and/or mismatch repair protein deficient (dMMR) endometrioid endometrial cancer must have previously received an immune checkpoint inhibitor.
- Unlimited prior hormonal therapy, targeted therapy (including immunotherapy), and/or antiangiogenic therapy will be permitted.
- Washout periods (due to risk of myelosuppression):
- Cytotoxic chemotherapy - 3 weeks.
- Radiation therapy - 2 weeks (NOTE: patients with radiation to \> 25% of the bone marrow are NOT eligible).
- Disease status:
- For PART I, evaluable disease or measurable disease required. NOTE: evaluable disease: defined as disease related abnormalities on radiographic imaging that do not meet RECIST 1.1 definitions for target lesions.
- For PART II, measurable disease by RECIST 1.1 is required. Patients will be required to undergo biopsy, which may be a non-target lesion but should not be the only RECIST measurable lesion. NOTE: Patients for PART II...
- Hemoglobin \>= 9 g/dL (in the absence of transfusion within 28 days prior to dosing)
- Absolute neutrophil count \>= 1,500 cells/mm\^3
- Platelet count \>= 100,000 cells/mm\^3
- Calculated creatinine clearance (CrCL) of \>= 50 mL/min by the Cockcroft-Gault formula
- Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level =\< 3 x ULN may be enrolled)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 x institutional ULN
- Patients with known history or current symptoms of cardiac disease or history of treatment with cardiotoxic agents should be New York Heart Association (NYHA) Functional Classification of class I or II.
- The effects of M1774 and ZEN003694 on the developing human fetus are unknown. For this reason and because BETi agents are known to be teratogenic, women of child-bearing potential must agree to use adequate...
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or how well it works assessment of the investigational regimen are eligible for...
- Patients with treated brain metastases are eligible if follow up brain imaging after central nervous system (CNS) directed therapy shows no evidence of progression, are off steroids, and are stable for at least 1 month.
- 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...
- PART II only: Participants must have known mutational status (wild-type or pathogenic or likely pathogenic alteration) for ARID1A by Next-Generation Sequencing. This can be determined according to local testing...
- Patients must be able to swallow oral medications (capsules and tablets) without chewing, breaking, crushing, opening, or otherwise altering the product formulation.
- Patients with co-morbidities:
- 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...
- Resolution of all toxicities of prior therapy or surgical procedures to baseline or grade 1 (except for hypothyroidism requiring medication, which must have resolved to Grade =\< 2), alopecia, and other toxicities...
What rules you out
- Patients who are receiving any other investigational agents.
- Patients who have received prior ATR, ATM, CHK, BET, EZH2, and/or PI3K inhibitors.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ZEN003694 or M1774 used in study.
- Patients taking proton pump inhibitors given decreased solubility of M1774 with increased pH. Proton pump inhibitors must be discontinued 7 days prior to initiating the trial.
- Patients with corrected QT (QTc) over 450msec that does not correct with correction of electrolyte abnormalities or family history of long QT syndrome.
- Patients with severe, active co-morbidity defined as follows:
- No active infection requiring parenteral antibiotics.
- Known hereditary diseases characterized by genetic defects of DNA repair mechanisms, including ataxia telangiectasia, Nijmegen breakage syndrome, Werner syndrome, Bloom Syndrome, Fanconi anemia, xeroderma pigmentosum...
- Pregnant and breastfeeding women are excluded from this study because ZEN003694 has the potential for teratogenic or abortifacient effects and M1774 is genotoxic in in vivo nonclinical studies. Patients who discontinue...
- Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible. Strong inhibitors or inducers of CYP3A4 must be discontinued at least 7 days prior to the first dose of...
- Patients receiving any medications or substances that are Factor Xa inhibitors are discouraged given concerns for thrombocytopenia (i.e., rivaroxaban, apixaban, betrixaban, edoxaban otamixaban, letaxaban, eribaxaban)...
- Serious gastrointestinal bleeding within 3 months, refractory nausea and vomiting, uncontrolled diarrhea, known malabsorption, significant small bowel resection or gastric bypass surgery, use of feeding tubes, presence...
- M1774 restrictions:
- Patients who cannot discontinue drugs that are strong inhibitors of CYP3A4 or CYP1A2.
- Patients who cannot discontinue drugs that use hMATE1 or hMATE2-K substrates.
The study team makes the final eligibility decision.
Where it's taking place
- Augusta, Georgia, United States
- Chicago, Illinois, United States
- Iowa City, Iowa, United States
- Detroit, Michigan, United States
- Albuquerque, New Mexico, United States
- Cleveland, Ohio, United States
- Columbus, Ohio, United States
- Oklahoma City, Oklahoma, United States
- Philadelphia, Pennsylvania, United States
- Providence, Rhode Island, United States
- Milwaukee, Wisconsin, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling female, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Augusta, Georgia, United States; Chicago, Illinois, United States; Iowa City, Iowa, United States; Detroit, Michigan, United States; Albuquerque, New Mexico, United States; Cleveland, Ohio, United States and 5 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.