Cervical Cancer, Endometrial Cancer
Conditions
Brief summary
This is a phase II study of rucaparib, a small molecule inhibitor poly (adenosine diphosphate \[ADP\]-ribose) polymerase (PARP), being tested in combination with bevacizumab in patients with recurrent cervical or endometrial cancer. The objective of this study is to determine the proportion of these patients who survive progression-free for at least 6 months while receiving this drug combination.
Detailed description
Patients who consent to participate in this study will receive treatment with rucaparib and bevacizumab until unacceptable toxicity or tumor progression. Subjects will take one rucaparib pill will be taken twice daily, and bevacizumab will be adimistered via IV onDay 1 of each 21 day cycle. Subjects will receive tests and procedures that are part of regular cancer care as well as those required for the purposes of this study. If there is no cancer found in scans after 6 cycles of treatment, patients may continue with study treatment for 1 year. Follow up visits will occur every 3 months for the first 2 years after treatment is completed and every 6 months for 3 additional years.
Interventions
DRUGRucaparib
Rucaparib 600mg PO BID daily
DRUGBevacizumab
Bevacizumab 15mg/kg IV on day 1 of each cycle
Sponsors
Clovis Oncology, Inc.
University of Oklahoma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. Patients with histologically-documented carcinoma of the cervix or endometrium. 2. Patients with measurable and/or evaluable lesions as defined by RECIST 1.1. 3. Women at least 18 years of age 4. Patients with persistent or recurrent squamous cell or adenocarcinoma of the cervix, or any carcinoma or carcinosarcoma of the endometrium who has undergone at least one prior line of systemic therapy. Prior bevacizumab is allowed. (Note: previous cisplatin during radiation therapy should NOT count as a prior line of systemic therapy). 5. ECOG performance status of 0, 1, or 2. 6. Patients should agree to have tumor biopsy for correlative studies.If the patients are unable to be safely biopsied and desire enrollment, they may be enrolled per principal investigator discretion. 7. Adequate organ function should be confirmed by the following laboratory values obtained ≤ 14 days prior to first dose of rucaparib. 8. Patients must have a life expectancy of at least 3 months ((to be able to complete one cycle of study treatment). 9. Patients should have no major existing co-morbidities or medical conditions that will preclude therapy in the view of the principal investigator. 10. Prior bevacizumab is allowed if off drug ≥ 28 days prior to study enrollment. 11. Women of childbearing potential must not be considering getting pregnant and must avoid pregnancy during the study and for at least six months after the last dose of rucaparib or longer if requested by local authorities.
Exclusion criteria
1. Have active second malignancy, i.e., patient known to have potentially fatal cancer present for which she may be (but not necessarily) currently receiving treatment; However patients with a history of malignancy that has been completely treated, with no evidence of that cancer currently, are permitted to enroll in the trial provided all chemotherapy was completed \>6 months prior and/or bone marrow transplant (BMT) \>2 years prior to first dose of rucaparib. 2. Prior treatment with any PARP inhibitor. 3. Untreated or symptomatic central nervous system (CNS) metastases.Patients with asymptomatic CNS metastases are eligible provided they have been clinically stable for at least 4 weeks. 4. Patients who have received treatment with chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C); or radiation, biologic/targeted agents, experimental drugs within 3 weeks prior to first dose of rucaparib; and/or ongoing adverse effects from such treatment \> NCI CTCAE Grade 1 (Grade 2 non-hematologic toxicity to most recent treatment may be permitted with prior advanced approval from Sponsor). 5. Hospitalization for bowel obstruction within 3 months prior to enrollment. 6. Patients must have no history of gross hemoptysis (defined as bright red blood of a ½ teaspoon or more) or coagulopathy. Patients with history of major tumor-related bleeding that is not controlled despite locoregional treatment or at high risk of recurrent tumor-related bleeding will be excluded. 7. Patients with history of hypertension must be well-controlled (≤150/100) on a stable regimen of anti-hypertensive therapy. 8. Patients with tumors that invaded major vessels (e.g. the carotid) as shown unequivocally by imaging studies will be excluded due to the possibility of increased risk for tumor bleeding with bevacizumab therapy. 9. Patients should not have a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment, or anticipation of need for major surgical procedure during the course of the study. No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to registration. No serious non-healing wound, ulcer, or bone fracture. 10. Patients should not have unstable angina or myocardial infarction within the previous 6 months; no uncontrolled hypertension; no symptomatic congestive heart failure; no serious cardiac arrhythmia requiring medication; no clinically significant peripheral vascular disease; no history of any CNS cerebrovascular ischemia or stroke within the last 6 months; no active serious infection. 11. Patients should not have other coexisting medical condition that would preclude full compliance with the study. 12. Patients may not be receiving any other investigational agents. 13. Patients should not have a history of prior severe infusion reaction to a monoclonal antibody. Patients with known hypersensitivity of Chinese hamster ovary cell products or other recombinant human antibodies. 14. Pregnant women are excluded from this study because rucaparib and bevacizumab have 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 rucaparib and bevacizumab, breastfeeding should be discontinued if the mother is treated with rucaparib and bevacizumab. Should a woman become pregnant or suspect she is pregnant while in this study, she should inform her treating physician immediately. 15. HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible drug interactions with rucaparib and bevacizumab.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Who Are Progression-free at 6 Months | 6 months | To estimate the proportion of pts treated w/bevacizumab who are progression-free. Progression for measurable disease per RECIST v1.1. Progression for pts with non-measurable disease at baseline is defined as increasing clinical, radiological, or histological evidence of disease since study entry. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Who Had Objective Tumor Response | up to 2 years | To estimate the proportion of patients treated with bevacizumab and rucaparib who have objective tumor response (complete or partial) |
| Number of Patients Who Experience Toxicity | up to 2 year | To determine the nature and degree of toxicity in combination of rucaparib and bevacizumab (Adverse Event Grade 3 and higher). |
| Median Overall Survival | up to 2 years | To estimate the median overall survival of patients treated with combination rucaparib and bevacizumab. |
| Median Progression-free Survival Time | up to 2 years | To estimate the progression-free survival (PFS) of patients with persistent or recurrent cervical or endometrial cancer treated with combination rucaparib and bevacizumab Progression for measurable disease per RECIST v1.1 Progression for patients with non-measurable disease at baseline is defined as increasing clinical, radiological, or histological evidence of disease since study entry. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at 3 cancer centers from June 2018 to Nov 2019. The first patient was enrolled on July 2, 2018 and the last patient was enrolled on November 8, 2019
Pre-assignment details
Of 49 enrolled participants, 33 met inclusion criteria and assign to the single arm treatment. Among 33 participants started treatment, 28 were evaluable for statistical analysis.
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab + Rucaparib Rucaparib: Rucaparib 600mg PO BID daily
Bevacizumab: Bevacizumab 15mg/kg IV on day 1 of each cycle | 33 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Protocol Violation | 2 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Bevacizumab + Rucaparib |
|---|---|
| Age, Continuous | 60.4 years STANDARD_DEVIATION 12.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 27 Participants |
| Region of Enrollment United States | 33 Participants |
| Sex: Female, Male Female | 33 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 29 / 33 |
| other Total, other adverse events | 33 / 33 |
| serious Total, serious adverse events | 14 / 33 |
Outcome results
Primary
Proportion of Patients Who Are Progression-free at 6 Months
To estimate the proportion of pts treated w/bevacizumab who are progression-free. Progression for measurable disease per RECIST v1.1. Progression for pts with non-measurable disease at baseline is defined as increasing clinical, radiological, or histological evidence of disease since study entry.
Time frame: 6 months
Population: Patients who met criteria for evaluability: Evaluable patients will be defined as patients with measurable and/or evaluable lesions who received at least cycle 1 doses of study treatment (one dose of IV bevacizumab and 21 days of rucaprib, PO, BID) and complete the first post-treatment CT or MRI for tumor assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab + Rucaparib | Proportion of Patients Who Are Progression-free at 6 Months | 0.29 Proportion of patients |
Secondary
Median Overall Survival
To estimate the median overall survival of patients treated with combination rucaparib and bevacizumab.
Time frame: up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab + Rucaparib | Median Overall Survival | 10.12 Months |
Secondary
Median Progression-free Survival Time
To estimate the progression-free survival (PFS) of patients with persistent or recurrent cervical or endometrial cancer treated with combination rucaparib and bevacizumab Progression for measurable disease per RECIST v1.1 Progression for patients with non-measurable disease at baseline is defined as increasing clinical, radiological, or histological evidence of disease since study entry.
Time frame: up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab + Rucaparib | Median Progression-free Survival Time | 3.83 Months |
Secondary
Number of Patients Who Experience Toxicity
To determine the nature and degree of toxicity in combination of rucaparib and bevacizumab (Adverse Event Grade 3 and higher).
Time frame: up to 2 year
Population: All patients who received treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bevacizumab + Rucaparib | Number of Patients Who Experience Toxicity | 22 Participants |
Secondary
Proportion of Patients Who Had Objective Tumor Response
To estimate the proportion of patients treated with bevacizumab and rucaparib who have objective tumor response (complete or partial)
Time frame: up to 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab + Rucaparib | Proportion of Patients Who Had Objective Tumor Response | 0.14 Proportion of patients |