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Bevacizumab and Rucaparib in Recurrent Carcinoma of the Cervix or Endometrium (Clovis-001)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03476798
Recruitment Status : Active, not recruiting
First Posted : March 26, 2018
Results First Posted : May 28, 2021
Last Update Posted : July 2, 2021
Sponsor:
Collaborator:
Clovis Oncology, Inc.
Information provided by (Responsible Party):
University of Oklahoma

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.

Condition or disease Intervention/treatment Phase
Cervical Cancer Endometrial Cancer Drug: Rucaparib Drug: Bevacizumab Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 49 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of Bevacizumab and Rucaparib in Recurrent Carcinoma of the Cervix or Endometrium
Actual Study Start Date : June 29, 2018
Actual Primary Completion Date : May 12, 2020
Estimated Study Completion Date : February 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Bevacizumab + Rucaparib Drug: Rucaparib
Rucaparib 600mg PO BID daily

Drug: Bevacizumab
Bevacizumab 15mg/kg IV on day 1 of each cycle




Primary Outcome Measures :
  1. Proportion of Patients Who Are Progression-free at 6 Months [ Time Frame: 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 Outcome Measures :
  1. Proportion of Patients Who Had Objective Tumor Response [ Time Frame: up to 2 years ]
    To estimate the proportion of patients treated with bevacizumab and rucaparib who have objective tumor response (complete or partial)

  2. Number of Patients Who Experience Toxicity [ Time Frame: up to 2 year ]
    To determine the nature and degree of toxicity in combination of rucaparib and bevacizumab (Adverse Event Grade 3 and higher).

  3. Median Overall Survival [ Time Frame: up to 2 years ]
    To estimate the median overall survival of patients treated with combination rucaparib and bevacizumab.

  4. Median Progression-free Survival Time [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03476798


Locations
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United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Oklahoma
Stephenson Cancer Center, University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73117
United States, Virginia
University of Virginia Cancer Center
Charlottesville, Virginia, United States, 22903
Sponsors and Collaborators
University of Oklahoma
Clovis Oncology, Inc.
Investigators
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Principal Investigator: Kathleen Moore, MD Obstetrics and Gynecology
  Study Documents (Full-Text)

Documents provided by University of Oklahoma:
Study Protocol  [PDF] April 1, 2020
Statistical Analysis Plan  [PDF] May 3, 2021
Informed Consent Form  [PDF] February 19, 2020

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Responsible Party: University of Oklahoma
ClinicalTrials.gov Identifier: NCT03476798    
Other Study ID Numbers: OU-SCC-Clovis-001
First Posted: March 26, 2018    Key Record Dates
Results First Posted: May 28, 2021
Last Update Posted: July 2, 2021
Last Verified: June 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Endometrial Neoplasms
Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Diseases
Bevacizumab
Rucaparib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action