Testing the Combination of Drugs M1774 and ZEN-3694 for the Treatment of Recurrent Ovarian and Endometrial Cancer

About the Study 

This study is for patients with clear cell or endometrioid ovarian or endometrial cancer which has returned or spread after other treatments. Patients with platinum-resistant high-grade serous ovarian cancer are also allowed to enroll in Part I of this study. This Phase I trial will test a new combination of two medications, M1774 and ZEN003694, that has been shown to significantly kill cancer cells and tumors in animal studies. 

What the Study Involves

The study is divided into two groups.

Group I: different drug combination doses are tested to identify the safe dose for patients.

• Patients receive the study drug, M1774 orally once daily, either on days 2-14 of cycle 1 and days 1-14 of subsequent cycles or
• Patients receive the study drug, M1774 orally once daily on days 1-14 of each cycle, and they study drug, ZEN-3694 orally once daily on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
• Patients also undergo collection of blood samples on study and X-ray, computed tomography (CT), or magnetic resonance imaging (MRI) throughout the trial.

Group 2: patients will be evaluated on the safety of the treatment, and also the activity of the treatment in two groups of patients: those with and without a mutation in the gene ARID1A.

• Patients in group 2 also undergo biopsies during screening and on-study, and X-ray, CT, or MRI, and collection of blood samples throughout the trial.

After study completion, patients are followed every 3 months for 2 years and then every 6 months for 3 years, or until the study has ended.

The ultimate goal of this study is to identify a new treatment for patients with hard-to-treat ovarian and endometrial cancers. 

This study is open to people:

• who have clear cell ovarian or endometrial cancer or endometrioid ovarian or endometrial cancer that has returned or spread after other treatments
• with platinum-resistant high-grade serous ovarian carcinoma may join group 1 of this study 
• 18 years of age or older
• 1-3 prior chemotherapies

This study is not open to people:

• who are receiving any other investigational agents
• who have received prior ATR, ATM, CHK, BET, EZH2, and/or PI3K inhibitors
• have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to ZEN003694 or M1774 used in the study
• taking proton pump inhibitor. Proton pump inhibitors must be discontinued 7 days prior to initiating the trial.
• with corrected QT or family history of long QT syndrome (a heart rhythm disorder)
• with known hereditary diseases characterized by genetic defects of DNA repair mechanisms
• pregnant or breastfeeding. Patients who discontinue breastfeeding are eligible for enrollment and may not resume breastfeeding until 1 month off treatment.
• receiving any medications or substances that are Factor Xa inhibitors ( a type of blood thinner) are discouraged, given concerns for low platelet counts and Factor IIa inhibitors
• with serious gastrointestinal bleeding within the past 3 months, nausea and vomiting, uncontrolled diarrhea, significant small bowel resection or gastric bypass surgery