Rucaparib vs Placebo Maintenance Therapy in Metastatic and Recurrent Endometrial Cancer

Study Overview
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Brief Summary
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This study seeks to determine the effectiveness of Rucaparib as maintenance therapy for metastatic and recurrent endometrial cancer, after 1-2 prior lines of therapy.

Detailed Description
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This is a phase II clinical trial, that administers a maintenance treatment after first line chemotherapy is complete. It is designed to have a 1:1 randomization technique. Half the participants who enter the study will receive the active ingredient, Rucaparib, while the other half will receive a placebo. Treatment will be until progression with follow up until death.

Official Title
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A Phase II, Randomized, Double-Blind Study of the Use of Rucaparib vs. Placebo Maintenance Therapy in Metastatic and Recurrent Endometrial Cancer

Conditions
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Metastatic Endometrial Cancer

Intervention / Treatment
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* Drug: Rucaparib
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In order to be eligible to participate in this study, an individual must meet all of the following criteria: Provision to sign and date the consent form. Stated willingness to comply with all study procedures and be available for the duration of the study. Be a female aged 18-89. Patients with a primary Stage III/IV or recurrent endometrial cancer. Patients have received at least one prior chemotherapy regimen and no more than two prior cytotoxic regimens (including hormonal therapy). Primary chemotherapy regimen must have consisted of at least 4 completed cycles and no more than 8 completed cycles. Previous cytotoxic regimen at least 4 weeks before initiation and no more than 8 weeks from initiation after last dose of previous therapy. Patients who receive radiation to the whole pelvis or at least 50% of the spine must complete radiation therapy and have at least 4 weeks' time elapse prior to initiation of drug. ECOG performance status of 0, 1 or 2. ANC > or = 1500 cells/microliters Platelet count > 100,000 microliters Hemoglobin > or = 9.0 g/dL Serum albumin > or = 2.5 g/dL Total bilirubin ≤ 1.5 x ULN AST and ALT ≤ 3.0 x ULN Serum Creatinine ≤ 1.5x ULN Exclusion Criteria: An individual who meets any of the following criteria will be excluded from participation in this study: Inability to comply with study and follow-up procedures Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the past 3 months, unstable arrhythmias, or unstable angina Known clinically significant liver disease defined as AST and ALT > 3.0 x ULN and/or Total bilirubin > or = 1.5 x ULN, or documented history of active viral, alcoholic, or other hepatitis, cirrhosis, and inherited liver disease Participation in investigational clinical trial within last 30 days History of significant chronic disease including HIV/AIDS or hepatitis C Inability to provide informed consent Known CNS malignancy or CNS metastases Patients with previous malignancy, other than endometrial, within the past 2 years from cycle 1, day 1, with the exception of those with negligible risk of metastasis or death, such as adequately controlled basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the breast. History of stroke or transient ischemic attack (TIA) within 3 months prior to cycle 1 day 1(C1D1) Women with prognosis for survival less than 6 months Patients who have progressed or have stable disease (SD) through most recent chemotherapy regimen Patients deemed otherwise clinically unfit for clinical trial per Investigator's discretion Patients with duodenal stent or other GI disorder/defect that would interfere with absorption of oral medication Female patients who maintain fertility potential and refuse to comply to use contraception and be followed for pregnancy by pregnancy testing Minor surgical procedure < or = 14 days or major surgeries < or = 28 days prior to first dose of treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Active ingredient vs placebo
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Ingredient<br>1:1 Randomization. Participants in this arm receive the active ingredient medication. | Drug: Rucaparib<br>* Participants allocated to the active ingredient arm will receive Rucaparib twice daily, 600mg, to be take by mouth. Patients will take the medication continuously over a 28 day cycle, until disease progression or other indication of discontinuation. Medication should be taken around the same time every day, with 8 or more ounces of water.<br>|
| Placebo Comparator: Placebo<br>1:1 Randomization. Participants in this arm receive the placebo medication. (Placebos do not contain active ingredients). | Drug: Placebo Oral Tablet<br>* Participants allocated to the placebo arm will receive a placebo tablet (that looks identical to the active ingredient tablet) twice daily, 600mg, to be take by mouth. Patients will take the medication continuously over a 28 day cycle, until disease progression or other indication of discontinuation. Tablet should be taken around the same time every day, with 8 or more ounces of water.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | Progression free survival is defined as cycle 1 day 1 (C1D1) till the time of progression as determined by RECIST 1.1 criteria or death. | Start of study to end of study, or death, whichever comes first, up to 48 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Overall survival is defined as cycle 1 day 1 (C1D1) till the time of death. | Start of study to death, up to 48 months. | 
| Overall Response Rate (ORR) | ORR is defined as how well the tumor responds to the medication based on RECIST 1.1 evaluation. | Start of study to end of study, or death, whichever comes first, up to 48 months. | 
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Safety and tolerability analysis of Rucaparib will be summarized by dose and severity as assessed by the Common Toxicity Criteria for Adverse Events (CTCAE) version 5 and relationship to study drug. | Start of study to end of study, or death, whichever comes first, up to 48 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rucaparib, Placebo, Randomized, Double Blind, Stage III/IV