Brief Title
Bevacizumab and Rucaparib in Recurrent Carcinoma of the Cervix or Endometrium
Official Title
A Phase II Trial of Bevacizumab and Rucaparib in Recurrent Carcinoma of the Cervix or Endometrium
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Proportion of Patients Who Are Progression-free at 6 Months
Secondary Outcome
Proportion of Patients Who Had Objective Tumor Response
Condition
Cervical Cancer
Intervention
Rucaparib
Study Arms / Comparison Groups
Bevacizumab + Rucaparib
Description:
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
49
Start Date
June 29, 2018
Completion Date
April 2023
Primary Completion Date
May 12, 2020
Eligibility Criteria
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.
Gender
Female
Ages
18 Years - 99 Years
Accepts Healthy Volunteers
No
Contacts
Kathleen Moore, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT03476798
Organization ID
OU-SCC-Clovis-001
Responsible Party
Sponsor
Study Sponsor
University of Oklahoma
Collaborators
Clovis Oncology, Inc.
Study Sponsor
Kathleen Moore, MD, Principal Investigator, Obstetrics and Gynecology
Verification Date
March 2023