Metastatic Endometrial Cancer
Conditions
Keywords
Rucaparib, Placebo, Randomized, Double Blind, Stage III/IV
Brief summary
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
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.
Interventions
DRUGRucaparib
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.
DRUGPlacebo Oral Tablet
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.
Sponsors
University of Colorado, Denver
Clovis Oncology, Inc.
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Active ingredient vs placebo
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 89 Years
Healthy volunteers
No
Inclusion criteria
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 1. Provision to sign and date the consent form. 2. Stated willingness to comply with all study procedures and be available for the duration of the study. 3. Be a female aged 18-89. 4. Patients with a primary Stage III/IV or recurrent endometrial cancer. 5. Patients have received at least one prior chemotherapy regimen and no more than two prior cytotoxic regimens (including hormonal therapy). 6. Primary chemotherapy regimen must have consisted of at least 4 completed cycles and no more than 8 completed cycles. 7. Previous cytotoxic regimen at least 4 weeks before initiation and no more than 8 weeks from initiation after last dose of previous therapy. 8. 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. 9. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2. 10. Absolute neutrophil count (ANC) \> or = 1500 cells/microliters 11. Platelet count \> 100,000 microliters 12. Hemoglobin \> or = 9.0 g/dL 13. Serum albumin \> or = 2.5 g/dL 14. Total bilirubin ≤ 1.5 x ULN (uppler limit of normal) 15. AST and ALT ≤ 3.0 x ULN 16. Serum Creatinine ≤ 1.5x ULN
Exclusion criteria
An individual who meets any of the following criteria will be excluded from participation in this study: 1. Inability to comply with study and follow-up procedures 2. 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 3. 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 4. Participation in investigational clinical trial within last 30 days 5. History of significant chronic disease including HIV/AIDS or hepatitis C 6. Inability to provide informed consent 7. Known central nervous system (CNS) malignancy or CNS metastases 8. 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. 9. History of stroke or transient ischemic attack (TIA) within 3 months prior to cycle 1 day 1(C1D1) 10. Women with prognosis for survival less than 6 months 11. Patients who have progressed or have stable disease (SD) through most recent chemotherapy regimen 12. Patients deemed otherwise clinically unfit for clinical trial per Investigator's discretion 13. Patients with duodenal stent or other GI disorder/defect that would interfere with absorption of oral medication 14. Female patients who maintain fertility potential and refuse to comply to use contraception and be followed for pregnancy by pregnancy testing 15. Minor surgical procedure \< or = 14 days or major surgeries \< or = 28 days prior to first dose of treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Up to 48 months. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to 48 months. | Overall survival is defined as cycle 1 day 1 (C1D1) till the time of death. |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Up to 48 months. | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORBradley Corr, MD
University of Colorado, Denver
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Ingredient 1:1 Randomization. Participants in this arm receive the active ingredient medication.
Rucaparib: 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. | 39 |
| Placebo 1:1 Randomization. Participants in this arm receive the placebo medication. (Placebos do not contain active ingredients).
Placebo Oral Tablet: 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. | 40 |
| Total | 79 |
Baseline characteristics
| Characteristic | Active Ingredient | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 21 Participants | 23 Participants | 44 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 17 Participants | 35 Participants |
| Age, Continuous | 66 years | 67 years | 66 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 2 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 35 Participants | 38 Participants | 73 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 33 Participants | 34 Participants | 67 Participants |
| Region of Enrollment United States | 39 participants | 40 participants | 79 participants |
| Sex: Female, Male Female | 39 Participants | 40 Participants | 79 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 39 | 1 / 40 |
| other Total, other adverse events | 37 / 39 | 27 / 40 |
| serious Total, serious adverse events | 3 / 39 | 1 / 40 |
Outcome results
Primary
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.
Time frame: Up to 48 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Active Ingredient | Progression Free Survival (PFS) | 28.1 months |
| Placebo | Progression Free Survival (PFS) | 8.7 months |
Secondary
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.
Time frame: Up to 48 months.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Ingredient | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | 37 Participants |
| Placebo | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | 27 Participants |
Secondary
Overall Survival (OS)
Overall survival is defined as cycle 1 day 1 (C1D1) till the time of death.
Time frame: Up to 48 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Active Ingredient | Overall Survival (OS) | NA months |
| Placebo | Overall Survival (OS) | 28.4 months |