Bevacizumab and Rucaparib in Recurrent Carcinoma of the Cervix or Endometrium
Condition: Cervical Cancer; Endometrial Cancer
MeSH terms: Endometrial Neoplasms
Intervention: Rucaparib; Bevacizumab
Intervention description: Rucaparib 600mg PO BID daily; Bevacizumab 15mg/kg IV on day 1 of each cycle
Intervention MeSH terms: Bevacizumab; Rucaparib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 49.0
Sex: Female
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No

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.
    

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.