- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03476798
Bevacizumab and Rucaparib in Recurrent Carcinoma of the Cervix or Endometrium (Clovis-001)
February 13, 2024 updated by: University of Oklahoma
A Phase II Trial of Bevacizumab and Rucaparib in Recurrent Carcinoma of the Cervix or Endometrium
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
49
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Minnesota
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Minneapolis, Minnesota, United States, 55455
- University of Minnesota
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Oklahoma
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Oklahoma City, Oklahoma, United States, 73117
- Stephenson Cancer Center, University of Oklahoma Health Sciences Center
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Virginia
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Charlottesville, Virginia, United States, 22903
- University of Virginia Cancer Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 99 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Patients with histologically-documented carcinoma of the cervix or endometrium.
- Patients with measurable and/or evaluable lesions as defined by RECIST 1.1.
- Women at least 18 years of age
- 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).
- ECOG performance status of 0, 1, or 2.
- 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.
- Adequate organ function should be confirmed by the following laboratory values obtained ≤ 14 days prior to first dose of rucaparib.
- Patients must have a life expectancy of at least 3 months ((to be able to complete one cycle of study treatment).
- Patients should have no major existing co-morbidities or medical conditions that will preclude therapy in the view of the principal investigator.
- Prior bevacizumab is allowed if off drug ≥ 28 days prior to study enrollment.
- 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:
- 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.
- Prior treatment with any PARP inhibitor.
- 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.
- 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).
- Hospitalization for bowel obstruction within 3 months prior to enrollment.
- 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.
- Patients with history of hypertension must be well-controlled (≤150/100) on a stable regimen of anti-hypertensive therapy.
- 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.
- 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.
- 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.
- Patients should not have other coexisting medical condition that would preclude full compliance with the study.
- Patients may not be receiving any other investigational agents.
- 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.
- 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.
- HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible drug interactions with rucaparib and bevacizumab.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Bevacizumab + Rucaparib
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Rucaparib 600mg PO BID daily
Bevacizumab 15mg/kg IV on day 1 of each cycle
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of Patients Who Are Progression-free at 6 Months
Time Frame: 6 months
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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. |
6 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of Patients Who Had Objective Tumor Response
Time Frame: up to 2 years
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To estimate the proportion of patients treated with bevacizumab and rucaparib who have objective tumor response (complete or partial)
|
up to 2 years
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Number of Patients Who Experience Toxicity
Time Frame: up to 2 year
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To determine the nature and degree of toxicity in combination of rucaparib and bevacizumab (Adverse Event Grade 3 and higher).
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up to 2 year
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Median Overall Survival
Time Frame: up to 2 years
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To estimate the median overall survival of patients treated with combination rucaparib and bevacizumab.
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up to 2 years
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Median Progression-free Survival Time
Time Frame: up to 2 years
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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.
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up to 2 years
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Kathleen Moore, MD, Obstetrics and Gynecology
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 29, 2018
Primary Completion (Actual)
May 12, 2020
Study Completion (Actual)
September 29, 2023
Study Registration Dates
First Submitted
March 19, 2018
First Submitted That Met QC Criteria
March 19, 2018
First Posted (Actual)
March 26, 2018
Study Record Updates
Last Update Posted (Actual)
February 15, 2024
Last Update Submitted That Met QC Criteria
February 13, 2024
Last Verified
February 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Uterine Neoplasms
- Genital Neoplasms, Female
- Uterine Diseases
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Genital Diseases
- Genital Diseases, Female
- Endometrial Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Poly(ADP-ribose) Polymerase Inhibitors
- Bevacizumab
- Rucaparib
Other Study ID Numbers
- OU-SCC-CLOVIS-001
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cervical Cancer
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University of California, San DiegoWithdrawnCervical Cancer | Cervical Cancer Stage | Cervical Cancer Stage IB2 | Cervical Cancer Stage IB1 | Cervical Cancer Stage I | Cervical Cancer Stage IB | Cervical Cancer Stage II | Cervical Cancer Stage IIa | Cervical Cancer, Stage IIB | Cervical Cancer, Stage III | Cervical Cancer Stage IIIB | Cervical Cancer... and other conditionsUnited States
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M.D. Anderson Cancer CenterWithdrawnStage IB3 Cervical Cancer FIGO 2018 | Stage II Cervical Cancer FIGO 2018 | Stage IIA Cervical Cancer FIGO 2018 | Stage IIA1 Cervical Cancer FIGO 2018 | Stage IIA2 Cervical Cancer FIGO 2018 | Stage IIB Cervical Cancer FIGO 2018 | Stage III Cervical Cancer FIGO 2018 | Stage IIIA Cervical Cancer FIGO... and other conditions
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Abramson Cancer Center of the University of PennsylvaniaWithdrawnCervical Cancer | Stage IB Cervical Cancer | Stage IIA Cervical Cancer | Stage IIB Cervical Cancer | Stage III Cervical Cancer | Stage IVA Cervical Cancer
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National Cancer Institute (NCI)CompletedCervical Adenocarcinoma | Cervical Squamous Cell Carcinoma | Stage IB Cervical Cancer | Stage IIA Cervical Cancer | Stage IIB Cervical Cancer | Stage III Cervical Cancer | Stage IVA Cervical Cancer | Stage IVB Cervical CancerUnited States
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Mayo ClinicNational Cancer Institute (NCI)RecruitingCervical Adenosquamous Carcinoma | Cervical Squamous Cell Carcinoma, Not Otherwise Specified | Recurrent Cervical Carcinoma | Stage IB3 Cervical Cancer FIGO 2018 | Stage II Cervical Cancer FIGO 2018 | Stage IIA Cervical Cancer FIGO 2018 | Stage IIA1 Cervical Cancer FIGO 2018 | Stage IIA2 Cervical... and other conditionsUnited States
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M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingStage IA Cervical Cancer | Stage IB Cervical Cancer | Stage IA1 Cervical Cancer | Stage IA2 Cervical Cancer | Stage IB1 Cervical Cancer | Stage IB2 Cervical Cancer | Stage IB3 Cervical CancerUnited States
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Shanghai First Maternity and Infant HospitalNot yet recruitingCervical Cancer, Stage IIB | Cervical Cancer Stage IIIB | Cervical Cancer Stage IIIA | Cervical Cancer, Stage IVA
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University of Southern CaliforniaNational Cancer Institute (NCI)CompletedRecurrent Cervical Cancer | Stage IVA Cervical Cancer | Stage IVB Cervical Cancer | Stage IIIA Cervical Cancer | Stage IIIB Cervical CancerUnited States
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Gynecologic Oncology GroupNational Cancer Institute (NCI)CompletedCervical Adenocarcinoma | Cervical Squamous Cell Carcinoma | Stage IB Cervical Cancer | Stage IIA Cervical Cancer | Stage IIB Cervical Cancer | Stage III Cervical Cancer | Stage IVA Cervical CancerUnited States
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Institut de Cancérologie de LorraineCompletedCervical Adenocarcinoma | Stage IB Cervical Cancer | Stage III Cervical Cancer | Stage II Cervical CancerFrance
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