- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01281852
Paclitaxel, Cisplatin, and Veliparib in Treating Patients With Advanced, Persistent, or Recurrent Cervical Cancer
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
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
California
-
Los Angeles, California, United States, 90033
- USC / Norris Comprehensive Cancer Center
-
-
Georgia
-
Augusta, Georgia, United States, 30912
- Augusta University Medical Center
-
-
Illinois
-
Chicago, Illinois, United States, 60637
- University of Chicago Comprehensive Cancer Center
-
-
Iowa
-
Iowa City, Iowa, United States, 52242
- University of Iowa/Holden Comprehensive Cancer Center
-
-
Maryland
-
Baltimore, Maryland, United States, 21287
- Johns Hopkins University/Sidney Kimmel Cancer Center
-
-
Mississippi
-
Jackson, Mississippi, United States, 39216
- University of Mississippi Medical Center
-
Pascagoula, Mississippi, United States, 39581
- Singing River Hospital
-
-
Missouri
-
Saint Louis, Missouri, United States, 63110
- Washington University School of Medicine
-
-
New York
-
New York, New York, United States, 10065
- Memorial Sloan Kettering Cancer Center
-
-
Ohio
-
Cleveland, Ohio, United States, 44106
- Case Western Reserve University
-
Cleveland, Ohio, United States, 44109
- MetroHealth Medical Center
-
Cleveland, Ohio, United States, 44195
- Cleveland Clinic Foundation
-
Columbus, Ohio, United States, 43214
- Riverside Methodist Hospital
-
Columbus, Ohio, United States, 43210
- Ohio State University Comprehensive Cancer Center
-
Mayfield Heights, Ohio, United States, 44124
- Hillcrest Hospital Cancer Center
-
-
Oklahoma
-
Oklahoma City, Oklahoma, United States, 73104
- University of Oklahoma Health Sciences Center
-
Tulsa, Oklahoma, United States, 74146
- Oklahoma Cancer Specialists and Research Institute-Tulsa
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States, 19107
- Thomas Jefferson University Hospital
-
-
Rhode Island
-
Providence, Rhode Island, United States, 02905
- Women and Infants Hospital
-
-
South Carolina
-
Charleston, South Carolina, United States, 29425
- Medical University of South Carolina
-
-
Texas
-
Dallas, Texas, United States, 75390
- UT Southwestern/Simmons Cancer Center-Dallas
-
Houston, Texas, United States, 77030
- M D Anderson Cancer Center
-
Houston, Texas, United States, 77026-1967
- Lyndon Baines Johnson General Hospital
-
-
Virginia
-
Charlottesville, Virginia, United States, 22908
- University of Virginia Cancer Center
-
Richmond, Virginia, United States, 23298
- Virginia Commonwealth University/Massey Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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.
|
Correlative studies
Given IV
Other Names:
Given IV
Other Names:
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Dose-limiting toxicities in the first course of treatment (Phase I)
Time Frame: 21 days
|
21 days
|
Frequency and severity of adverse effects as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events v. 4.0
Time Frame: Within 30 days of last protocol treatment
|
Within 30 days of last protocol treatment
|
Objective tumor response (complete or partial response) (Phase II)
Time Frame: Up to 5 years
|
Up to 5 years
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Progression-free survival (Phase II)
Time Frame: From study entry to time of progression or death, whichever occurs first, assessed up to 5 years
|
From study entry to time of progression or death, whichever occurs first, assessed up to 5 years
|
Overall survival (Phase II)
Time Frame: From study entry to time of death or the date of last contact, assessed up to 5 years
|
From study entry to time of death or the date of last contact, assessed up to 5 years
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of patients with tumors that demonstrate loss of the FancD2 foci formation
Time Frame: Baseline
|
The loss of FancD2 foci formation is associated with progression-free survival, overall survival, and response.
|
Baseline
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Ritu Salani, NRG Oncology
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Uterine Neoplasms
- Genital Neoplasms, Female
- Uterine Cervical Diseases
- Uterine Diseases
- Disease Attributes
- Neoplasms, Complex and Mixed
- Neoplasms, Squamous Cell
- Uterine Cervical Neoplasms
- Carcinoma
- Recurrence
- Carcinoma, Squamous Cell
- Carcinoma, Adenosquamous
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Poly(ADP-ribose) Polymerase Inhibitors
- Paclitaxel
- Cisplatin
- Albumin-Bound Paclitaxel
- Veliparib
Other Study ID Numbers
- NCI-2011-02661 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- U10CA027469 (U.S. NIH Grant/Contract)
- GOG-0076HH (Other Identifier: CTEP)
- CDR0000693745
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cervical Adenocarcinoma
-
Catalysis SLCompletedCervical Carcinoma Stage II | Cervical Carcinoma Stage III | Cervical Carcinoma Stage IV | Endometrial Adenocarcinoma Stage II | Endometrial Adenocarcinoma Stage III | Endometrial Adenocarcinoma Stage IVCuba
-
Merck Sharp & Dohme LLCCompletedPrevention of HPV Types 16- and 18-related Cervical Cancer, Cervical Intraepithelial Neoplasia (CIN) 1/2/3, and Cervical Adenocarcinoma in SituChina
-
Institut de Cancérologie de LorraineCompletedCervical Adenocarcinoma | Stage IB Cervical Cancer | Stage III Cervical Cancer | Stage II Cervical CancerFrance
-
Tampere University HospitalKarolinska Institutet; Tampere University; European UnionEnrolling by invitationCervical Intraepithelial Neoplasia Grade 2/3 | Adenocarcinoma in SituFinland
-
Shanghai Gynecologic Oncology GroupFudan UniversityCompletedCervical Adenocarcinoma | Cervical Squamous Cell Carcinoma | Malignant Neoplasm of Cervix Stage IB1 | Stage IIA1 Cervical CancerChina
-
Merck Sharp & Dohme LLCCompletedCervical Cancer | Cervical Intraepithelial Neoplasia | Adenocarcinoma in Situ
-
National Cancer Institute (NCI)CompletedCervical Adenocarcinoma | Cervical Squamous Cell Carcinoma | Stage IB Cervical Cancer | Stage IIA Cervical Cancer | Stage IIB Cervical Cancer | Stage III Cervical Cancer | Stage IVA Cervical Cancer | Stage IVB Cervical CancerUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)CompletedCervical Adenocarcinoma | Cervical Squamous Cell Carcinoma | Stage IB Cervical Cancer | Stage IIA Cervical Cancer | Stage IIB Cervical Cancer | Stage III Cervical Cancer | Stage IVA Cervical CancerUnited States
-
National Cancer Institute (NCI)CompletedCervical Adenocarcinoma | Cervical Squamous Cell Carcinoma | Stage IVA Cervical Cancer AJCC v6 and v7 | Recurrent Cervical Carcinoma | Human Papillomavirus Infection | Stage IVB Cervical Cancer AJCC v6 and v7United States, Canada
-
National Cancer Institute (NCI)TerminatedCervical Adenocarcinoma | Cervical Adenosquamous Carcinoma | Cervical Carcinoma | Cervical Carcinoma, Non-SquamousTypeUnited States
Clinical Trials on Laboratory Biomarker Analysis
-
ECOG-ACRIN Cancer Research GroupNational Cancer Institute (NCI)CompletedProstate Cancer
-
Children's Oncology GroupNational Cancer Institute (NCI)Completed
-
National Cancer Institute (NCI)Recruiting
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)Not yet recruitingLynch Syndrome | Recurrent Uterine Corpus Carcinoma | Stage I Uterine Corpus Cancer | Stage II Uterine Corpus Cancer | Stage III Uterine Corpus Cancer | Stage IV Uterine Corpus CancerUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)Not yet recruitingRecurrent Uterine Corpus Carcinoma | Stage III Uterine Corpus Cancer | Stage IV Uterine Corpus CancerUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)RecruitingStage IIIA Ovarian Cancer | Stage IIIB Ovarian Cancer | Stage IIIC Ovarian Cancer | Stage IV Ovarian CancerUnited States
-
Ohio State University Comprehensive Cancer CenterActive, not recruitingLung Cancer | Radiation Toxicity | Adult Brain TumorUnited States
-
National Cancer Institute (NCI)Active, not recruitingMalignant NeoplasmUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor | Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor | Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor | Askin TumorUnited States, Canada, Puerto Rico, Australia, New Zealand, Switzerland
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed