Veliparib, Topotecan Hydrochloride, and Filgrastim or Pegfilgrastim in Treating Patients With Persistent or Recurrent Cervical Cancer
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
Other: Laboratory Biomarker Analysis
Drug: Topotecan Hydrochloride
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Evaluation of ABT-888 (NCI Supplied Agent: ABT-888, NSC #737664), Topotecan (NSC # 609699) and Filgrastim or Pegfilgrastim in the Treatment of Persistent or Recurrent Squamous or Non-squamous Cell Carcinoma of the Cervix|
- Tumor Response [ Time Frame: Every other cycle for first 6 months; then every 3 months thereafter until disease progression confirmed; and at any other time if clinically indicted based on symptoms or physical signs suggestive of progressive disease ]Complete and Partial Tumor Response as Assessed by RECIST 1.1
- Number of Patients With Dose-limiting Toxicities (in Safety lead-in) [ Time Frame: Up to 21 days ]A dose-limiting toxicity (DLT) is assessed by NCI CTCAE v4, occurring during cycle 1 of therapy.
- Adverse Events (Grade 3 or Higher) During Treatment Period [ Time Frame: During treatment period and up to 30 days after stopping the study treatment. ]Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v4.0.
- Progression-free Survival [ Time Frame: From study entry to disease progression, death or date of last contact, whichever occurs first, up to 5 years of follow-up. ]Progression-free survival is the period of time from study entry to time of disease progression, death or date of last contact, whichever occurs first
- Overall Survival [ Time Frame: From study entry to death or last contact, up to 5 years of follow-up. ]Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.
- Duration of Objective Response [ Time Frame: Every other cycle for first 6 months; then every 3 months thereafter until disease progression confirmed; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease. ]Duration of objective response is defined as the duration from the time measurement criteria is met for partial or complete response by RECIST 1.1, whichever is first recorded, until the first date the recurrent or progressive disease is objectively documented.
|Study Start Date:||February 2011|
|Study Completion Date:||January 2016|
|Primary Completion Date:||January 2016 (Final data collection date for primary outcome measure)|
Experimental: Treatment (veliparib, topotecan hydrochloride, filgrastim)
Patients receive veliparib PO twice daily and topotecan hydrochloride IV over 30 minutes once daily on days 1-5. Patients also receive, according to institutional standard, filgrastim SC beginning on day 6, 7, or 8 and continuing until hematopoietic recovery or pegfilgrastim SC on day 6, 7, or 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Other Names:Other: Laboratory Biomarker Analysis
Correlative studiesBiological: Pegfilgrastim
Other Names:Drug: Topotecan Hydrochloride
Other Names:Drug: Veliparib
I. To estimate the antitumor activity (objective response rate by RECIST 1.1) of ABT-888 (veliparib) 10 mg administered orally twice a day on days 1 to 5 with topotecan (topotecan hydrochloride) 0.6 mg/m^2 administered IV once daily on days 1 to 5 of each cycle in patients with persistent or recurrent carcinoma of the cervix.
II. To determine the nature and degree of toxicity of ABT-888 and topotecan in patients with persistent or recurrent carcinoma of the cervix.
I. To determine the duration of progression-free survival and overall survival.
I. To determine whether evidence of an interaction exists between study treatments and tumor expression of poly(ADP-ribos)ylation of E2 protein, E6/E7 proteins, and p53R2 in relation to progression-free and overall survival or metastasis. (Translational) II. To explore the association between methylation of FanCF and BRCA in pre-treatment tumor samples and pre- and post-treatment biopsy samples and response, progression-free and overall survival of patients, and/or metastasis. (Translational)
Patients receive veliparib orally (PO) twice daily and topotecan hydrochloride intravenously (IV) over 30 minutes once daily on days 1-5. Patients also receive, according to institutional standard, filgrastim subcutaneously (SC) beginning on day 6, 7, or 8 and continuing until hematopoietic recovery or pegfilgrastim SC on day 6, 7, or 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Tumor tissue samples may be collected periodically for translational studies.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01266447
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|Principal Investigator:||Charles Kunos||NRG Oncology|