Clinical Trials /

Bevacizumab and Rucaparib in Recurrent Carcinoma of the Cervix or Endometrium

NCT03476798

Description:

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.

Related Conditions:
  • Cervical Adenocarcinoma
  • Cervical Squamous Cell Carcinoma
  • Endometrial Carcinoma
  • Uterine Corpus Carcinosarcoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: 8985
  • NCT ID: NCT03476798

Conditions

  • Cervical Cancer
  • Endometrial Cancer

Interventions

DrugSynonymsArms
RucaparibBevacizumab + Rucaparib
BevacizumabBevacizumab + Rucaparib

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Bevacizumab + RucaparibExperimental
  • Rucaparib
  • Bevacizumab

Eligibility Criteria

        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.

          -  Patients who have progressed tumor after first line treatment for Stage 4B, recurrent
             or persistent squamous cell or adenocarcinoma of the cervix, or adenocarcinoma of the
             endometrium.

          -  ECOG performance status of 0, 1, or 2.

          -  Patients must agree to have tumor biopsy for correlative studies.

          -  Patients must have acceptable organ and marrow function.

          -  Patients must have a life expectancy of at least 3 months.

          -  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.

          -  Female patients of reproductive potential and their male partners must agree to
             practice total abstinence or use a highly effective method of contraception prior to
             study entry, during treatment and for 6 months following the last dose of rucaparib.

          -  Negative serum pregnancy test result less than 3 days prior to administration of the
             first dose of rucaparib.

        Exclusion Criteria:

          -  Patients who 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.

          -  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 should not have a history of thrombosis (e.g. pulmonary embolism or deep
             venous thrombosis) and should not be on therapeutic anticoagulation (prophylactic use
             of warfarin 1 mg per day is allowed) and INR should be less than 1.5 at registration.

          -  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.

          -  Patients who are breast feeding should discontinue before going on study.

          -  HIV-positive patients receiving combination anti-retroviral therapy are excluded from
             the study because of possible drug interactions with rucaparib and bevacizumab.
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of patients who survive progression-free
Time Frame:6 months
Safety Issue:
Description:To estimate the proportion of patients treated with bevacizumab who are progression-free.

Secondary Outcome Measures

Measure:Number of patients who have objective tumor response
Time Frame:6 months
Safety Issue:
Description:To estimate the proportion of patients treated with bevacizumab and rucaparib who have objective tumor response (complete or partial)
Measure:Number of patients who experience toxicity
Time Frame:6 months
Safety Issue:
Description:To determine the nature and degree of toxicity in combination of rucaparib and bevacizumab.
Measure:Number of patients with overall survival
Time Frame:5 years
Safety Issue:
Description:To estimate the overall survival of patients treated with combination rucaparib and bevacizumab.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Oklahoma

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