Paclitaxel, Cisplatin, and Veliparib in Treating Patients With Advanced, Persistent, or Recurrent Cervical Cancer

Inclusion Criteria:

• Patients must have primary stage IVB, recurrent, or persistent squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix that is not amenable to curative treatment with surgery and/or radiotherapy

  • Histologic documentation of the original primary tumor is required via the pathology report
• All patients in the phase I portion must have received prior chemoradiation
• Measurable disease not required for patients in the phase I portion

• All patients in the phase II portion must have measurable disease as defined by RECIST 1.1

  • Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded)
  • Each lesion must be ≥ 10 mm when measured by CT scan, MRI, or caliper measurement by clinical exam; or ≥ 20 mm when measured by chest x-ray
  • Lymph nodes must be ≥ 15 mm in short axis when measured by CT scan or MRI

• Patients in the phase II portion must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1

  • Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiotherapy
• No patients with history or evidence, upon physical examination, of CNS disease, including primary brain tumor or brain metastases, within the past 6 months of the first date of treatment on this study
• GOG performance status 0-2
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9 g/dL
• Creatinine normal OR creatinine clearance ≥ 60 mL/min
• Calcium, magnesium, phosphate, and potassium normal
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 3 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Women of child-bearing potential must agree to use adequate contraception (hormonal, barrier method of birth control, or abstinence) prior to study entry and for the duration of study participation
• Able to swallow medication
• Free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection [UTI])
• Peripheral neuropathy (sensory and motor) ≤ grade 1
• No history of other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies, within the past 3 years.
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to veliparib or other agents used in study
• No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• No history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA), or subarachnoid hemorrhage within the past 6 months of the first date of treatment on this study
• No other concurrent investigational agents
• Recovered from effects of recent surgery, radiotherapy, or other therapy

• At least 1 week since prior hormonal therapy directed at the malignant tumor

  • Continuation of hormone replacement therapy is permitted
• At least 6 weeks since prior chemoradiotherapy
• At least 3 weeks since prior radiotherapy alone
• At least 6 weeks since prior major surgery
• No prior cancer treatment that contraindicates this protocol therapy
• No prior veliparib or other PARP inhibitors

• No prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of cervical cancer within the last 3 years

  • Prior radiotherapy for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than 3 years prior to registration and the patient remains free of recurrent or metastatic disease

• No prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of cervical cancer within the last 3 years

  • Prior adjuvant chemotherapy for localized breast cancer allowed, provided that it was completed more than 3 years prior to registration and the patient remains free of recurrent or metastatic disease

  • No prior chemotherapy for cervical cancer except when used concurrently with radiotherapy

    • No patients who have received concurrent paclitaxel with radiation therapy