Veliparib, Topotecan Hydrochloride, and Filgrastim or Pegfilgrastim in Treating Patients With Persistent or Recurrent Cervical Cancer
Condition: Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Recurrent Cervical Carcinoma; Stage III Cervical Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer
MeSH terms: Carcinoma; Uterine Cervical Neoplasms; Carcinoma, Small Cell; Small Cell Lung Carcinoma; Carcinoma, Adenosquamous; Recurrence
Intervention: Filgrastim; Laboratory Biomarker Analysis; Pegfilgrastim; Topotecan Hydrochloride; Veliparib
Intervention description: Given SC; Correlative studies; Given SC; Given IV; Given PO
Intervention MeSH terms: Topotecan; Veliparib; Lenograstim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 27.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II clinical trial is studying the how well veliparib, topotecan hydrochloride, and
      filgrastim or pegfilgrastim work in treating patients with persistent or recurrent cervical
      cancer. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed
      for cell growth. Drugs used in chemotherapy, such as topotecan hydrochloride, work in
      different ways to stop the growth of tumor cells, either by killing the cells or by blocking
      them from dividing. Giving veliparib with chemotherapy may kill more tumor cells. Filgrastim
      or pegfilgrastim may cause the body to make more blood cells and help it recover from the
      side effects of chemotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have persistent or recurrent squamous cell carcinoma, adenosquamous
             carcinoma, adenocarcinoma or non-squamous cell carcinoma of the cervix with documented
             disease progression; histological documentation of the original primary tumor is
             required via the pathology report

          -  All patients 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 diameter to be recorded); each lesion must be >= 10 mm when
             measured by computed tomography (CT), magnetic resonance imaging (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 or MRI

          -  Patient 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 radiation
             therapy

          -  Patients must not be eligible for a higher priority Gynecologic Oncology Group (GOG)
             protocol, if one exists; in general, this would refer to any active GOG Phase III
             protocol or Rare Tumor protocol for the same patient population

          -  Patients must have a GOG performance status of 0, 1, or 2

          -  Recovery from effects of recent surgery, radiotherapy, or chemotherapy

          -  Patients should be free of active infection requiring antibiotics

          -  Any hormonal therapy directed at the malignant tumor must be discontinued at least one
             week prior to registration; continuation of hormone replacement therapy is permitted

          -  Any other prior therapy directed at the malignant tumor, including chemotherapy,
             biologic/targeted (non-cytotoxic) therapy and immunologic agents must be discontinued
             at least three weeks prior to registration; all side effects must have resolved to =<
             grade 1 or stabilized, prior to enrolling on this study

          -  Any prior radiation therapy must be completed at least 4 weeks prior to registration

          -  Patients MUST have had one prior systemic chemotherapeutic regimen for management of
             advanced, metastatic, or recurrent squamous or non-squamous cell carcinoma of the
             cervix; chemotherapy administered concurrent with primary radiation is not counted as
             a systemic chemotherapy regimen (e.g.; weekly cisplatin); adjuvant chemotherapy given
             following the completion of radiation therapy (or concurrent chemotherapy and
             radiation therapy) is not counted as a systemic chemotherapy regimen (e.g.; paclitaxel
             and carboplatin for up to 4 cycles)

          -  Patients who are registered during the safety lead-in portion of this protocol are
             required to have prior pelvic radiation

          -  Patients must have NOT received more than one previous cytotoxic chemotherapy regimen
             (either with single or combination cytotoxic drug therapy)

          -  Patients are allowed to receive, but are not required to receive, biologic/targeted
             (non-cytotoxic) therapy as part of their one prior systemic chemotherapeutic regimen;
             patients are allowed to receive, but are not required to receive, biologic/targeted
             (non-cytotoxic) therapy for management of recurrent or persistent disease

          -  Patients MUST not be eligible for further curative intent surgical or pelvic radiation
             treatment for management of recurrent or persistent disease as determined by treating
             physicians

          -  Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl

          -  Platelets greater than or equal to 100,000/mcl

          -  Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN)

          -  Bilirubin less than or equal to 1.5 x ULN

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal
             to 3 x ULN

          -  Alkaline phosphatase less than or equal to 2.5 x ULN

          -  Neuropathy (sensory and motor) less than or equal to grade 1

          -  Patients must have signed an approved informed consent and authorization permitting
             release of personal health information

          -  Patients must meet pre-entry requirements

          -  Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for
             the duration of study participation; should a woman become pregnant or suspect she is
             pregnant while participating in this study, she should inform her treating physician
             immediately

          -  Patients must have the ability to swallow pills whole

        Exclusion Criteria:

          -  Patients are excluded who have had prior therapy with ABT-888 (veliparib), poly
             (ADP)-ribose polymerase inhibitors, or topotecan

          -  Patient with a history of other invasive malignancies, with the exception of
             non-melanoma skin cancer and other specific malignancies are excluded if there is any
             evidence of other malignancy being present within the last three years; patients are
             also excluded if their previous cancer treatment contraindicates this protocol therapy

          -  Patients who have received prior radiotherapy to any portion of the abdominal cavity
             or pelvis OTHER THAN for the treatment of cervical cancer within the last three years
             are excluded; prior radiation for localized cancer of the breast, head and neck, or
             skin is permitted, provided that it was completed more than three years prior to
             registration, and the patient remains free of recurrent or metastatic disease

          -  Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER
             THAN for the treatment of cervical cancer within the last three years are excluded;
             patients may have received prior adjuvant chemotherapy for cancer, provided that it
             was completed more than three years prior to registration, and that the patient
             remains free of recurrent or metastatic disease

          -  Patients with seizures or history of seizures are ineligible

          -  Patients with history or evidence upon physical examination of central nervous system
             (CNS) disease, including primary brain tumor, any CNS metastases, or history of
             cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or
             subarachnoid hemorrhage within six months of the first date of treatment on this
             study, are ineligible; patients with CNS metastases must be stable for > 3 months
             after treatment and off steroid treatment prior to study enrollment