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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01266447
Other study ID # NCI-2011-02659
Secondary ID NCI-2011-02659GO
Status Completed
Phase Phase 2
First received
Last updated
Start date February 2011
Est. completion date January 2016

Study information

Verified date August 2019
Source National Cancer Institute (NCI)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Description:

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.


Recruitment information / eligibility

Status Completed
Enrollment 27
Est. completion date January 2016
Est. primary completion date January 2016
Accepts healthy volunteers No
Gender Female
Age group 18 Years and older
Eligibility 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

Study Design


Intervention

Biological:
Filgrastim
Given SC
Other:
Laboratory Biomarker Analysis
Correlative studies
Biological:
Pegfilgrastim
Given SC
Drug:
Topotecan Hydrochloride
Given IV
Veliparib
Given PO

Locations

Country Name City State
United States Abington Memorial Hospital Abington Pennsylvania
United States Southwest Gynecologic Oncology Associates Inc Albuquerque New Mexico
United States University of New Mexico Cancer Center Albuquerque New Mexico
United States Michigan Cancer Research Consortium CCOP Ann Arbor Michigan
United States Saint Joseph Mercy Hospital Ann Arbor Michigan
United States University of Colorado Cancer Center - Anschutz Cancer Pavilion Aurora Colorado
United States University Medical Center Brackenridge Austin Texas
United States Johns Hopkins University/Sidney Kimmel Cancer Center Baltimore Maryland
United States PeaceHealth Medical Group PC Bellingham Washington
United States Saint Alphonsus Cancer Care Center-Boise Boise Idaho
United States Harrison HealthPartners Hematology and Oncology-Bremerton Bremerton Washington
United States Harrison Medical Center Bremerton Washington
United States State University of New York Downstate Medical Center Brooklyn New York
United States Cooper Hospital University Medical Center Camden New Jersey
United States Case Western Reserve University Cleveland Ohio
United States Riverside Methodist Hospital Columbus Ohio
United States Clements University Hospital Dallas Texas
United States Parkland Memorial Hospital Dallas Texas
United States UT Southwestern/Simmons Cancer Center-Dallas Dallas Texas
United States Zale Lipshy University Hospital Dallas Texas
United States Oakwood Hospital and Medical Center Dearborn Michigan
United States Decatur Memorial Hospital Decatur Illinois
United States Saint John Hospital and Medical Center Detroit Michigan
United States Providence Regional Cancer Partnership Everett Washington
United States Hurley Medical Center Flint Michigan
United States Genesys Regional Medical Center Grand Blanc Michigan
United States Smilow Cancer Hospital Care Center at Saint Francis Hartford Connecticut
United States Sudarshan K Sharma MD Limted-Gynecologic Oncology Hinsdale Illinois
United States Indiana University/Melvin and Bren Simon Cancer Center Indianapolis Indiana
United States University of Iowa/Holden Comprehensive Cancer Center Iowa City Iowa
United States Allegiance Health Jackson Michigan
United States University of Mississippi Medical Center Jackson Mississippi
United States Borgess Medical Center Kalamazoo Michigan
United States Bronson Methodist Hospital Kalamazoo Michigan
United States West Michigan Cancer Center Kalamazoo Michigan
United States Sparrow Hospital Lansing Michigan
United States Women's Cancer Center of Nevada Las Vegas Nevada
United States Saint Mary Mercy Hospital Livonia Michigan
United States North Shore University Hospital Manhasset New York
United States Lake University Ireland Cancer Center Mentor Ohio
United States Skagit Valley Hospital Regional Cancer Care Center Mount Vernon Washington
United States D N Greenwald Center Mukwonago Wisconsin
United States The Hospital of Central Connecticut New Britain Connecticut
United States Long Island Jewish Medical Center New Hyde Park New York
United States North Shore-LIJ Health System/Center for Advanced Medicine New Hyde Park New York
United States Oconomowoc Memorial Hospital-ProHealth Care Inc Oconomowoc Wisconsin
United States University of Oklahoma Health Sciences Center Oklahoma City Oklahoma
United States UC Irvine Health/Chao Family Comprehensive Cancer Center Orange California
United States Florida Hospital Orlando Orlando Florida
United States Fox Chase Cancer Center Philadelphia Pennsylvania
United States Saint Joseph Mercy Oakland Pontiac Michigan
United States Saint Joseph Mercy Port Huron Port Huron Michigan
United States Harrison HealthPartners Hematology and Oncology-Poulsbo Poulsbo Washington
United States Women and Infants Hospital Providence Rhode Island
United States Virginia Commonwealth University/Massey Cancer Center Richmond Virginia
United States Saint Mary's of Michigan Saginaw Michigan
United States Memorial University Medical Center Savannah Georgia
United States Fred Hutchinson Cancer Research Center Seattle Washington
United States Group Health Cooperative-Seattle Seattle Washington
United States Northwest Hospital Seattle Washington
United States Pacific Gynecology Specialists Seattle Washington
United States Seattle Cancer Care Alliance Seattle Washington
United States Swedish Medical Center-First Hill Seattle Washington
United States University of Washington Medical Center Seattle Washington
United States Olympic Medical Cancer Care Center Sequim Washington
United States Cancer Care Northwest - Spokane South Spokane Washington
United States Rockwood Cancer Treatment Center-DHEC-Downtown Spokane Washington
United States Cancer Research for the Ozarks NCORP Springfield Missouri
United States CoxHealth South Hospital Springfield Missouri
United States Memorial Medical Center Springfield Illinois
United States Mercy Hospital Springfield Springfield Missouri
United States MultiCare Tacoma General Hospital Tacoma Washington
United States Saint Joseph Medical Center Tacoma Washington
United States Scott and White Memorial Hospital Temple Texas
United States Oklahoma Cancer Specialists and Research Institute-Tulsa Tulsa Oklahoma
United States Providence Saint Mary Regional Cancer Center Walla Walla Washington
United States Waukesha Memorial Hospital Waukesha Wisconsin
United States Wenatchee Valley Hospital and Clinics Wenatchee Washington

Sponsors (2)

Lead Sponsor Collaborator
National Cancer Institute (NCI) NRG Oncology

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Tumor Response Complete and Partial Tumor Response as Assessed by RECIST 1.1. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), Complete Response (CR), disappearance of all target and non-target lesions without evidence of new lesion; Partial Response (PR), at least 30% decrease in the sum of the longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD with no unequivocal progression of non-target lesions and no evidence of new lesion. Complete or partial response requires confirmation at greater than or equal to 4 weeks from initial documentation. Every other cycle for first 6 months; then every 3 months thereafter until disease progression confirmed; and at any other time if clinically indicted based on symptoms or physical signs suggestive of progressive disease. The average time was 2.3 months
Primary Number of Patients With Dose-limiting Toxicities (in Safety lead-in) A dose-limiting toxicity (DLT) is assessed by NCI CTCAE v4, occurring during cycle 1 of therapy.: A dose-limiting toxicity (DLT) is defined as either hematologic or non-hematologic toxicity assessed by NCI CTCAE v4, occurring during cycle 1 of therapy, which cause any of the following: For hematologic toxicity - dose delay of greater than 2 weeks due to failure to recover counts, Treatment related febrile neutropenia, grade 4 neutropenia lasting >7 days, treatment related grade 4 thrombocytopenia or clinically significant bleeding with grade 3 thrombocytopenia. For non-hematologic toxicity; study treatment related grade 3 or 4 non-hematological toxicity (excluding anorexia, constipation, fatigue, hypersensitivity/allergic reaction to one of the study drugs, nausea & vomiting, and grade 3 dehydration), grade 4 nausea and vomiting for >48 hours despite maximum medical management, electrolyte imbalance of > or equal to grade 3 that can be replaced within 48 hours; any drug related death Up to 21 days
Primary Adverse Events (Grade 3 or Higher) During Treatment Period Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v4.0. During treatment period and up to 30 days after stopping the study treatment.The average of study treatment time was 2.3 months.
Secondary Progression-free Survival Progression-free survival is the period of time from study entry to time of disease progression, death or date of last contact, whichever occurs first. Progression is defined as at least a 20% increase in the sum of the longest dimensions (LD) of target lesions taking as reference the smallest sum LD recorded since study entry, or unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions, or global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or death due to disease without prior objective documentation of progression. From study entry to disease progression, death or date of last contact, whichever occurs first, up to 5 years of follow-up.
Secondary Overall Survival Overall survival is defined as the duration of time from study entry to time of death or the date of last contact. From study entry to death or last contact, up to 5 years of follow-up.
Secondary Duration of Objective Response Duration of objective response is defined as the duration from the time measurement criteria is met for partial or complete response by RECIST 1.1, whichever is first recorded, until the first date the recurrent or progressive disease is objectively documented. Per Response Evaluation Criteria in Solid Tumors (RECIST) criteria Complete Response (CR), disappearance of all target and non-target lesions without evidence of new lesion; Partial Response (PR), at least 30% decrease in the sum of the longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD with no unequivocal progression of non-target lesions and no evidence of new lesion. Complete or partial response requires confirmation at greater than or equal to 4 weeks from initial documentation. Every other cycle for first 6 months; then every 3 months until disease progression confirmed; and at any other time if clinically indicated based on symptoms or signs suggestive of progressive disease.The average of study treatment time was 2.3 months.
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