Veliparib, Topotecan Hydrochloride, and Filgrastim or Pegfilgrastim in Treating Patients With Persistent or Recurrent Cervical Cancer

NCT ID: NCT01266447

Last Updated: 2019-08-08

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

27 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-02-28

Study Completion Date

2016-01-31

Brief Summary

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This phase II clinical trial is studying the how well veliparib, topotecan hydrochloride, and filgrastim or pegfilgrastim work in treating patients with persistent or recurrent cervical cancer. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as topotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by blocking them from dividing. Giving veliparib with chemotherapy may kill more tumor cells. Filgrastim or pegfilgrastim may cause the body to make more blood cells and help it recover from the side effects of chemotherapy.

Detailed Description

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PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

I. To determine the duration of progression-free survival and overall survival.

TERTIARY OBJECTIVES:

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)

OUTLINE:

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.

Conditions

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Cervical Adenocarcinoma 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

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 (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.

Group Type EXPERIMENTAL

Filgrastim

Intervention Type BIOLOGICAL

Given SC

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Pegfilgrastim

Intervention Type BIOLOGICAL

Given SC

Topotecan Hydrochloride

Intervention Type DRUG

Given IV

Veliparib

Intervention Type DRUG

Given PO

Interventions

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Filgrastim

Given SC

Intervention Type BIOLOGICAL

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Pegfilgrastim

Given SC

Intervention Type BIOLOGICAL

Topotecan Hydrochloride

Given IV

Intervention Type DRUG

Veliparib

Given PO

Intervention Type DRUG

Other Intervention Names

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Filgrastim XM02 G-CSF Neupogen r-metHuG-CSF Recombinant Methionyl Human Granulocyte Colony Stimulating Factor rG-CSF Tbo-filgrastim Tevagrastim Filgrastim SD-01 filgrastim-SD/01 HSP-130 Neulasta Pegfilgrastim Biosimilar HSP-130 SD-01 SD-01 sustained duration G-CSF Hycamptamine Hycamtin SKF S-104864-A Topotecan HCl topotecan hydrochloride (oral) ABT-888 PARP-1 inhibitor ABT-888

Eligibility Criteria

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Inclusion Criteria

* Patients must have persistent or recurrent squamous cell carcinoma, adenosquamous carcinoma, adenocarcinoma or non-squamous cell carcinoma of the cervix with documented disease progression; histological documentation of the original primary tumor is required via the pathology report
* All patients must have measurable disease as defined by RECIST 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter 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
* Patient 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 not be eligible for a higher priority Gynecologic Oncology Group (GOG) protocol, if one exists; in general, this would refer to any active GOG Phase III protocol or Rare Tumor protocol for the same patient population
* Patients must have a GOG performance status of 0, 1, or 2
* Recovery from effects of recent surgery, radiotherapy, or chemotherapy
* Patients should be free of active infection requiring antibiotics
* 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
* Any other prior therapy directed at the malignant tumor, including chemotherapy, biologic/targeted (non-cytotoxic) therapy and immunologic agents must be discontinued at least three weeks prior to registration; all side effects must have resolved to =\< grade 1 or stabilized, prior to enrolling on this study
* Any prior radiation therapy must be completed at least 4 weeks prior to registration
* Patients MUST have had one prior systemic chemotherapeutic regimen for management of advanced, metastatic, or recurrent squamous or non-squamous cell carcinoma of the cervix; chemotherapy administered concurrent with primary radiation is not counted as a systemic chemotherapy regimen (e.g.; weekly cisplatin); adjuvant chemotherapy given following the completion of radiation therapy (or concurrent chemotherapy and radiation therapy) is not counted as a systemic chemotherapy regimen (e.g.; paclitaxel and carboplatin for up to 4 cycles)
* Patients who are registered during the safety lead-in portion of this protocol are required to have prior pelvic radiation
* Patients must have NOT received more than one previous cytotoxic chemotherapy regimen (either with single or combination cytotoxic drug therapy)
* Patients are allowed to receive, but are not required to receive, biologic/targeted (non-cytotoxic) therapy as part of their one prior systemic chemotherapeutic regimen; patients are allowed to receive, but are not required to receive, biologic/targeted (non-cytotoxic) therapy for management of recurrent or persistent disease
* Patients MUST not be eligible for further curative intent surgical or pelvic radiation treatment for management of recurrent or persistent disease as determined by treating physicians
* Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl
* Platelets greater than or equal to 100,000/mcl
* Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN)
* 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 must meet pre-entry requirements
* Women of child-bearing potential and men 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
* Patients must have the ability to swallow pills whole

Exclusion Criteria

* Patients are excluded who have had prior therapy with ABT-888 (veliparib), poly (ADP)-ribose polymerase inhibitors, or topotecan
* Patient 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 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 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 with seizures or history of seizures are ineligible
* Patients with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, any CNS metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of treatment on this study, are ineligible; patients with CNS metastases must be stable for \> 3 months after treatment and off steroid treatment prior to study enrollment
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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Charles Kunos

Role: PRINCIPAL_INVESTIGATOR

NRG Oncology

Locations

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UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, United States

Site Status

University of Colorado Cancer Center - Anschutz Cancer Pavilion

Aurora, Colorado, United States

Site Status

Smilow Cancer Hospital Care Center at Saint Francis

Hartford, Connecticut, United States

Site Status

The Hospital of Central Connecticut

New Britain, Connecticut, United States

Site Status

Florida Hospital Orlando

Orlando, Florida, United States

Site Status

Memorial University Medical Center

Savannah, Georgia, United States

Site Status

Saint Alphonsus Cancer Care Center-Boise

Boise, Idaho, United States

Site Status

Decatur Memorial Hospital

Decatur, Illinois, United States

Site Status

Sudarshan K Sharma MD Limted-Gynecologic Oncology

Hinsdale, Illinois, United States

Site Status

Memorial Medical Center

Springfield, Illinois, United States

Site Status

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 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

Saint Joseph Mercy Hospital

Ann Arbor, Michigan, United States

Site Status

Michigan Cancer Research Consortium CCOP

Ann Arbor, Michigan, United States

Site Status

Oakwood Hospital and Medical Center

Dearborn, Michigan, United States

Site Status

Saint John Hospital and Medical Center

Detroit, Michigan, United States

Site Status

Hurley Medical Center

Flint, Michigan, United States

Site Status

Genesys Regional Medical Center

Grand Blanc, Michigan, United States

Site Status

Allegiance Health

Jackson, Michigan, United States

Site Status

Borgess Medical Center

Kalamazoo, Michigan, United States

Site Status

Bronson Methodist Hospital

Kalamazoo, Michigan, United States

Site Status

West Michigan Cancer Center

Kalamazoo, Michigan, United States

Site Status

Sparrow Hospital

Lansing, Michigan, United States

Site Status

Saint Mary Mercy Hospital

Livonia, Michigan, United States

Site Status

Saint Joseph Mercy Oakland

Pontiac, Michigan, United States

Site Status

Saint Joseph Mercy Port Huron

Port Huron, Michigan, United States

Site Status

Saint Mary's of Michigan

Saginaw, Michigan, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Cancer Research for the Ozarks NCORP

Springfield, Missouri, United States

Site Status

Mercy Hospital Springfield

Springfield, Missouri, United States

Site Status

CoxHealth South Hospital

Springfield, Missouri, United States

Site Status

Women's Cancer Center of Nevada

Las Vegas, Nevada, United States

Site Status

Cooper Hospital University Medical Center

Camden, New Jersey, United States

Site Status

Southwest Gynecologic Oncology Associates Inc

Albuquerque, New Mexico, United States

Site Status

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States

Site Status

State University of New York Downstate Medical Center

Brooklyn, New York, United States

Site Status

North Shore University Hospital

Manhasset, New York, United States

Site Status

Long Island Jewish Medical Center

New Hyde Park, New York, United States

Site Status

North Shore-LIJ Health System/Center for Advanced Medicine

New Hyde Park, New York, United States

Site Status

Case Western Reserve University

Cleveland, Ohio, United States

Site Status

Riverside Methodist Hospital

Columbus, Ohio, United States

Site Status

Lake University Ireland Cancer Center

Mentor, 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

Abington Memorial Hospital

Abington, Pennsylvania, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Women and Infants Hospital

Providence, Rhode Island, United States

Site Status

University Medical Center Brackenridge

Austin, Texas, United States

Site Status

Parkland Memorial Hospital

Dallas, Texas, United States

Site Status

Zale Lipshy University Hospital

Dallas, Texas, United States

Site Status

Clements University Hospital

Dallas, Texas, United States

Site Status

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States

Site Status

Scott and White Memorial Hospital

Temple, Texas, United States

Site Status

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, United States

Site Status

PeaceHealth Medical Group PC

Bellingham, Washington, United States

Site Status

Harrison HealthPartners Hematology and Oncology-Bremerton

Bremerton, Washington, United States

Site Status

Harrison Medical Center

Bremerton, Washington, United States

Site Status

Providence Regional Cancer Partnership

Everett, Washington, United States

Site Status

Skagit Valley Hospital Regional Cancer Care Center

Mount Vernon, Washington, United States

Site Status

Harrison HealthPartners Hematology and Oncology-Poulsbo

Poulsbo, Washington, United States

Site Status

Pacific Gynecology Specialists

Seattle, Washington, United States

Site Status

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Site Status

Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

Group Health Cooperative-Seattle

Seattle, Washington, United States

Site Status

Swedish Medical Center-First Hill

Seattle, Washington, United States

Site Status

Northwest Hospital

Seattle, Washington, United States

Site Status

University of Washington Medical Center

Seattle, Washington, United States

Site Status

Olympic Medical Cancer Care Center

Sequim, Washington, United States

Site Status

Cancer Care Northwest - Spokane South

Spokane, Washington, United States

Site Status

Rockwood Cancer Treatment Center-DHEC-Downtown

Spokane, Washington, United States

Site Status

MultiCare Tacoma General Hospital

Tacoma, Washington, United States

Site Status

Saint Joseph Medical Center

Tacoma, Washington, United States

Site Status

Providence Saint Mary Regional Cancer Center

Walla Walla, Washington, United States

Site Status

Wenatchee Valley Hospital and Clinics

Wenatchee, Washington, United States

Site Status

D N Greenwald Center

Mukwonago, Wisconsin, United States

Site Status

Oconomowoc Memorial Hospital-ProHealth Care Inc

Oconomowoc, Wisconsin, United States

Site Status

Waukesha Memorial Hospital

Waukesha, Wisconsin, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2011-02659

Identifier Type: REGISTRY

Identifier Source: secondary_id

GOG-0127W

Identifier Type: -

Identifier Source: secondary_id

CDR0000691281

Identifier Type: -

Identifier Source: secondary_id

GOG-0127W

Identifier Type: OTHER

Identifier Source: secondary_id

GOG-0127W

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180868

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10CA027469

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-02659

Identifier Type: -

Identifier Source: org_study_id

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