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

Information source: National Cancer Institute (NCI)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Recurrent Cervical Carcinoma; Stage IVB Cervical Cancer

Intervention: Cisplatin (Drug); Laboratory Biomarker Analysis (Other); Paclitaxel (Drug); Veliparib (Drug)

Phase: Phase 1/Phase 2

Status: Active, not recruiting

Sponsored by: National Cancer Institute (NCI)

Official(s) and/or principal investigator(s):
Ritu Salani, Principal Investigator, Affiliation: NRG Oncology

Summary

This phase I/II clinical trial studies the side effects and best dose of veliparib when given together with paclitaxel and cisplatin and to see how well they work in treating patients with cervical cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment or that has come back. Drugs used in chemotherapy, such as paclitaxel and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving more than one drug (combination chemotherapy) and giving chemotherapy together with veliparib may kill more tumor cells.

Clinical Details

Official title: A Limited Access Phase I/II Trial of Paclitaxel, Cisplatin and CTEP Supplied Agent ABT-888 (Veliparib) (NSC#737664) in the Treatment of Advanced, Persistent, or Recurrent Carcinoma of the Cervix

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Dose-limiting toxicities in the first course of treatment (Phase I)

Frequency and severity of adverse effects as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events v. 4.0

Objective tumor response (complete or partial response) (Phase II)

Secondary outcome:

Overall survival (Phase II)

Progression-free survival (Phase II)

Detailed description: PRIMARY OBJECTIVES: I. To determine the maximum-tolerated dose (MTD) and dose-limiting toxicities of ABT-888 (veliparib) when combined with cisplatin and paclitaxel in women with advanced, persistent, or recurrent cervical cancer. II. To examine the safety of administering ABT-888 when combined with cisplatin and paclitaxel. III. Once the recommended phase II dose is established, to estimate the efficacy of cisplatin, paclitaxel, and ABT-888 with respect to objective tumor response in patients with advanced, persistent, or recurrent carcinoma of the cervix. SECONDARY OBJECTIVES: I. To examine the effects of this regimen on progression-free survival and overall survival. TERTIARY OBJECTIVES: I. To determine the proportion of patients with advanced, persistent, or recurrent cancer of the cervix whose tumors demonstrate loss of the Fanconi anemia group D2 (FancD2) foci formation. III. To determine the association between loss of FancD2 foci formation and progression-free survival, overall survival, and response in this patient population. OUTLINE: This is a phase I, dose-escalation study of veliparib followed by a phase II study. Patients receive paclitaxel intravenously (IV) over 3 hours on day 1, cisplatin IV over 1 hour on day 2, and veliparib orally (PO) on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Female.

Criteria:

Inclusion Criteria:

- Patients must have primary stage IVB, recurrent or persistent squamous cell

carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix which is not amenable to curative treatment with surgery and/or radiation therapy; histologic documentation of the original primary tumor is required via the pathology report

- All patients in the phase II portion must have measurable disease as defined by

Response Evaluation Criteria in Solid Tumors (RECIST) 1. 1; measureable 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 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; measurable disease is not required for participation in the phase I portion of this study

- 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 radiation therapy

- Patients must have a Gynecologic Oncology Group (GOG) Performance Status of 0, 1, or

2

- Recovery from effects of recent surgery, radiotherapy or other therapy

- Patients should be free of active infection requiring antibiotics (with the

exception of uncomplicated urinary tract infection [UTI])

- 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

- At least six weeks must have elapsed from the last administration of

chemoradiotherapy, and at least three weeks must have elapsed from the last administration of radiation therapy alone; at least six weeks must have elapsed from the time of any major surgical procedure prior to randomization

- Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl

- Platelets greater than or equal to100,000/mcl

- Hemoglobin >= 9 gm/dL

- Creatinine less than or equal to institutional upper limit normal (ULN) or calculated

creatinine clearance (Cockcroft-Gault) >= 60 ml/min

- Calcium, magnesium, phosphate, and potassium levels within institutional normal

limits

- 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 of childbearing potential must have a negative pregnancy test prior to the

study entry and be practicing an effective form of contraception; women of child-bearing potential 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

- PHASE I: All patients must have received prior chemoradiation

- PHASE I: Patients do not need to have measurable disease

Exclusion Criteria:

- Patients with prior treatment with ABT-888 or other poly adenosine phosphate (ADP)

ribose polymerase (PARP) inhibitors

- Patients 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 the 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 localized breast 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 previously treated with chemotherapy for cervical cancer except when used

concurrently with radiation therapy and/or as adjuvant therapy

- Chemotherapy administered concurrent with primary radiation (e. g., weekly

cisplatin) is allowed; adjuvant chemotherapy given following the completion of radiation therapy (or concurrent chemotherapy and radiation therapy) is allowed (e. g., paclitaxel and carboplatin for up to 4 cycles)

- Patients may not be receiving any other investigational agents

- Patients with a history of allergic reactions attributed to compounds of similar

chemical or biologic composition to ABT-888 or other agents used in study

- Patients with 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

- Pregnant women are excluded from this study; breastfeeding should be discontinued if

the mother is treated with ABT-888

- Patients with history or evidence upon physical examination of central nervous system

(CNS) disease, including primary brain tumor, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within 6 months of the first date of treatment on this study

- Patients who are unable to swallow medication

- Patients who are breast feeding should be excluded

Locations and Contacts

USC / Norris Comprehensive Cancer Center, Los Angeles, California 90033, United States

Georgia Regents University Medical Center, Augusta, Georgia 30912, United States

University of Chicago Comprehensive Cancer Center, Chicago, Illinois 60637, United States

University of Iowa/Holden Comprehensive Cancer Center, Iowa City, Iowa 52242, United States

Johns Hopkins University/Sidney Kimmel Cancer Center, Baltimore, Maryland 21287, United States

University of Mississippi Medical Center, Jackson, Mississippi 39216, United States

Singing River Hospital, Pascagoula, Mississippi 39581, United States

Washington University School of Medicine, Saint Louis, Missouri 63110, United States

Memorial Sloan-Kettering Cancer Center, New York, New York 10065, United States

MetroHealth Medical Center, Cleveland, Ohio 44109, United States

Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, United States

Riverside Methodist Hospital, Columbus, Ohio 43214, United States

Hillcrest Hospital Cancer Center, Mayfield Heights, Ohio 44124, United States

University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, United States

Tulsa Cancer Institute, Tulsa, Oklahoma 74146, United States

Thomas Jefferson University Hospital, Philadelphia, Pennsylvania 19107, United States

Women and Infants Hospital, Providence, Rhode Island 02905, United States

Medical University of South Carolina, Charleston, South Carolina 29425, United States

UT Southwestern/Simmons Cancer Center-Dallas, Dallas, Texas 75390, United States

Lyndon Baines Johnson General Hospital, Houston, Texas 77026-1967, United States

University of Virginia Cancer Center, Charlottesville, Virginia 22908, United States

Virginia Commonwealth University/Massey Cancer Center, Richmond, Virginia 23298, United States

Additional Information

Starting date: April 2011
Last updated: June 3, 2015

Page last updated: August 23, 2015

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