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

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT01281852

Collaborator

NRG Oncology (Other)

Enrollment

Locations

Arm

Actual Duration (Months)

1.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase I 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.

Condition or Disease	Intervention/Treatment	Phase
Cervical Adenocarcinoma Cervical Adenosquamous Carcinoma Cervical Squamous Cell Carcinoma, Not Otherwise Specified Recurrent Cervical Carcinoma Stage IVB Cervical Cancer AJCC v6 and v7	Drug: Cisplatin Other: Laboratory Biomarker Analysis Drug: Paclitaxel Drug: Veliparib	Phase 1

Detailed Description

PRIMARY OBJECTIVES:

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.
To examine the safety of administering ABT-888 when combined with cisplatin and paclitaxel.
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:

To examine the effects of this regimen on progression-free survival and overall survival.

TERTIARY OBJECTIVES:

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.
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.

Study Design

Study Type:

Interventional

Actual Enrollment :

37 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Limited Access Phase I 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

Actual Study Start Date :

Mar 14, 2011

Actual Primary Completion Date :

Feb 11, 2017

Actual Study Completion Date :

Feb 11, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (paclitaxel, cisplatin, veliparib) Patients receive paclitaxel IV over 3 hours on day 1, cisplatin IV over 1 hour on day 2, and veliparib PO on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Drug: Cisplatin Given IV Other Names: Abiplatin Blastolem Briplatin CDDP Cis-diammine-dichloroplatinum Cis-diamminedichloridoplatinum Cis-diamminedichloro Platinum (II) Cis-diamminedichloroplatinum Cis-dichloroammine Platinum (II) Cis-platinous Diamine Dichloride Cis-platinum Cis-platinum II Cis-platinum II Diamine Dichloride Cismaplat Cisplatina Cisplatinum Cisplatyl Citoplatino Citosin Cysplatyna DDP Lederplatin Metaplatin Neoplatin Peyrone''s Chloride Peyrone''s Salt Placis Plastistil Platamine Platiblastin Platiblastin-S Platinex Platinol Platinol- AQ Platinol-AQ Platinol-AQ VHA Plus Platinoxan Platinum Platinum Diamminodichloride Platiran Platistin Platosin Other: Laboratory Biomarker Analysis Correlative studies Drug: Paclitaxel Given IV Other Names: Anzatax Asotax Bristaxol Praxel Taxol Taxol Konzentrat Drug: Veliparib Given PO Other Names: ABT-888 PARP-1 inhibitor ABT-888

Arm

Intervention/Treatment

Experimental: Treatment (paclitaxel, cisplatin, veliparib)

Patients receive paclitaxel IV over 3 hours on day 1, cisplatin IV over 1 hour on day 2, and veliparib PO on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Cisplatin

Given IV

Other Names:

Abiplatin

Blastolem

Briplatin

CDDP

Cis-diammine-dichloroplatinum

Cis-diamminedichloridoplatinum

Cis-diamminedichloro Platinum (II)

Cis-diamminedichloroplatinum

Cis-dichloroammine Platinum (II)

Cis-platinous Diamine Dichloride

Cis-platinum

Cis-platinum II

Cis-platinum II Diamine Dichloride

Cismaplat

Cisplatina

Cisplatinum

Cisplatyl

Citoplatino

Citosin

Cysplatyna

DDP

Lederplatin

Metaplatin

Neoplatin

Peyrone''s Chloride

Peyrone''s Salt

Placis

Plastistil

Platamine

Platiblastin

Platiblastin-S

Platinex

Platinol

Platinol- AQ

Platinol-AQ

Platinol-AQ VHA Plus

Platinoxan

Platinum

Platinum Diamminodichloride

Platiran

Platistin

Platosin

Other: Laboratory Biomarker Analysis

Correlative studies

Drug: Paclitaxel

Given IV

Other Names:

Anzatax

Asotax

Bristaxol

Praxel

Taxol

Taxol Konzentrat

Drug: Veliparib

Given PO

Other Names:

ABT-888

PARP-1 inhibitor ABT-888

Outcome Measures

Primary Outcome Measures

Dose-limiting toxicities in the first course of treatment (Phase I) [21 days]
Frequency and severity of adverse effects as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events v. 4.0 [Within 30 days of last protocol treatment]
Objective tumor response (complete or partial response) (Phase II) [Up to 5 years]

Secondary Outcome Measures

Progression-free survival (Phase II) [From study entry to time of progression or death, whichever occurs first, assessed up to 5 years]
Overall survival (Phase II) [From study entry to time of death or the date of last contact, assessed up to 5 years]

Other Outcome Measures

Proportion of patients with tumors that demonstrate loss of the FancD2 foci formation [Baseline]
The loss of FancD2 foci formation is associated with progression-free survival, overall survival, and response.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	USC / Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
2	Augusta University Medical Center	Augusta	Georgia	United States	30912
3	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
4	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
5	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287
6	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
7	Singing River Hospital	Pascagoula	Mississippi	United States	39581
8	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
9	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
10	Case Western Reserve University	Cleveland	Ohio	United States	44106
11	MetroHealth Medical Center	Cleveland	Ohio	United States	44109
12	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
13	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
14	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
15	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio	United States	44124
16	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
17	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma	United States	74146
18	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
19	Women and Infants Hospital	Providence	Rhode Island	United States	02905
20	Medical University of South Carolina	Charleston	South Carolina	United States	29425
21	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
22	Lyndon Baines Johnson General Hospital	Houston	Texas	United States	77026-1967
23	M D Anderson Cancer Center	Houston	Texas	United States	77030
24	University of Virginia Cancer Center	Charlottesville	Virginia	United States	22908
25	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298