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

NCT ID: NCT01281852

Last Updated: 2019-07-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

37 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-03-14

Study Completion Date

2017-02-11

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Cervical Adenocarcinoma Cervical Adenosquamous Carcinoma Cervical Squamous Cell Carcinoma, Not Otherwise Specified Recurrent Cervical Carcinoma Stage IVB Cervical Cancer AJCC v6 and v7

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Cisplatin

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Paclitaxel

Intervention Type DRUG

Given IV

Veliparib

Intervention Type DRUG

Given PO

Interventions

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Cisplatin

Given IV

Intervention Type DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Paclitaxel

Given IV

Intervention Type DRUG

Veliparib

Given PO

Intervention Type DRUG

Other Intervention Names

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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 Anzatax Asotax Bristaxol Praxel Taxol Taxol Konzentrat ABT-888 PARP-1 inhibitor ABT-888

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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NRG Oncology

OTHER

Sponsor Role collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ritu Salani

Role: PRINCIPAL_INVESTIGATOR

NRG Oncology

Locations

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USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

Augusta University Medical Center

Augusta, Georgia, United States

Site Status

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

Site Status

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Singing River Hospital

Pascagoula, Mississippi, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Case Western Reserve University

Cleveland, Ohio, United States

Site Status

MetroHealth Medical Center

Cleveland, Ohio, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status

Riverside Methodist Hospital

Columbus, Ohio, United States

Site Status

Hillcrest Hospital Cancer Center

Mayfield Heights, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Oklahoma Cancer Specialists and Research Institute-Tulsa

Tulsa, Oklahoma, United States

Site Status

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Site Status

Women and Infants Hospital

Providence, Rhode Island, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States

Site Status

Lyndon Baines Johnson General Hospital

Houston, Texas, United States

Site Status

M D Anderson Cancer Center

Houston, Texas, United States

Site Status

University of Virginia Cancer Center

Charlottesville, Virginia, United States

Site Status

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, United States

Site Status

Countries

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United States

References

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Thaker PH, Salani R, Brady WE, Lankes HA, Cohn DE, Mutch DG, Mannel RS, Bell-McGuinn KM, Di Silvestro PA, Jelovac D, Carter JS, Duan W, Resnick KE, Dizon DS, Aghajanian C, Fracasso PM. A phase I trial of paclitaxel, cisplatin, and veliparib in the treatment of persistent or recurrent carcinoma of the cervix: an NRG Oncology Study (NCT#01281852). Ann Oncol. 2017 Mar 1;28(3):505-511. doi: 10.1093/annonc/mdw635.

Reference Type DERIVED
PMID: 27998970 (View on PubMed)

Other Identifiers

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NCI-2011-02661

Identifier Type: REGISTRY

Identifier Source: secondary_id

GOG-0076HH

Identifier Type: -

Identifier Source: secondary_id

CDR0000693745

Identifier Type: -

Identifier Source: secondary_id

GOG-0076HH

Identifier Type: OTHER

Identifier Source: secondary_id

GOG-0076HH

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA027469

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-02661

Identifier Type: -

Identifier Source: org_study_id

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