Clinical trial NCT01266447: Veliparib, Topotecan Hydrochloride, and Filgrastim or Pegfilgrastim in Treating Patients With Persistent or Recurrent Cervical Cancer
Official title: A Phase II Evaluation of ABT-888 (NCI Supplied Agent: ABT-888, NSC #737664), Topotecan (NSC # 609699) and Filgrastim or Pegfilgrastim in the Treatment of Persistent or Recurrent Squamous or Non-squamous Cell Carcinoma of the Cervix
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: NRG Oncology
First posted: 2010-12-24
Enrollment: 27
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Tumor Response
timeFrame: 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
measure: Number of Patients With Dose-limiting Toxicities (in Safety lead-in)
timeFrame: Up to 21 days
measure: Adverse Events (Grade 3 or Higher) During Treatment Period
timeFrame: During treatment period and up to 30 days after stopping the study treatment.The average of study treatment time was 2.3 months.
Secondary outcomes:
measure: Progression-free Survival
timeFrame: From study entry to disease progression, death or date of last contact, whichever occurs first, up to 5 years of follow-up.
measure: Overall Survival
timeFrame: From study entry to death or last contact, up to 5 years of follow-up.
measure: Duration of Objective Response
timeFrame: 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.
Other outcomes:
Locations:
city: Orange
country: United States
facility: UC Irvine Health/Chao Family Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center - Anschutz Cancer Pavilion
state: Colorado
city: Hartford
country: United States
facility: Smilow Cancer Hospital Care Center at Saint Francis
state: Connecticut
city: New Britain
country: United States
facility: The Hospital of Central Connecticut
state: Connecticut
city: Orlando
country: United States
facility: Florida Hospital Orlando
state: Florida
city: Savannah
country: United States
facility: Memorial University Medical Center
state: Georgia
city: Boise
country: United States
facility: Saint Alphonsus Cancer Care Center-Boise
state: Idaho
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Hinsdale
country: United States
facility: Sudarshan K Sharma MD Limted-Gynecologic Oncology
state: Illinois
city: Springfield
country: United States
facility: Memorial Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University/Melvin and Bren Simon Cancer Center
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa/Holden Comprehensive Cancer Center
state: Iowa
city: Baltimore
country: United States
facility: Johns Hopkins University/Sidney Kimmel Cancer Center
state: Maryland
city: Ann Arbor
country: United States
facility: Saint Joseph Mercy Hospital
state: Michigan
city: Ann Arbor
country: United States
facility: Michigan Cancer Research Consortium CCOP
state: Michigan
city: Dearborn
country: United States
facility: Oakwood Hospital and Medical Center
state: Michigan
city: Detroit
country: United States
facility: Saint John Hospital and Medical Center
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Grand Blanc
country: United States
facility: Genesys Regional Medical Center
state: Michigan
city: Jackson
country: United States
facility: Allegiance Health
state: Michigan
city: Kalamazoo
country: United States
facility: Borgess Medical Center
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Lansing
country: United States
facility: Sparrow Hospital
state: Michigan
city: Livonia
country: United States
facility: Saint Mary Mercy Hospital
state: Michigan
city: Pontiac
country: United States
facility: Saint Joseph Mercy Oakland
state: Michigan
city: Port Huron
country: United States
facility: Saint Joseph Mercy Port Huron
state: Michigan
city: Saginaw
country: United States
facility: Saint Mary's of Michigan
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Springfield
country: United States
facility: Cancer Research for the Ozarks NCORP
state: Missouri
city: Springfield
country: United States
facility: Mercy Hospital Springfield
state: Missouri
city: Springfield
country: United States
facility: CoxHealth South Hospital
state: Missouri
city: Las Vegas
country: United States
facility: Women's Cancer Center of Nevada
state: Nevada
city: Camden
country: United States
facility: Cooper Hospital University Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: Southwest Gynecologic Oncology Associates Inc
state: New Mexico
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Brooklyn
country: United States
facility: State University of New York Downstate Medical Center
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New Hyde Park
country: United States
facility: Long Island Jewish Medical Center
state: New York
city: New Hyde Park
country: United States
facility: North Shore-LIJ Health System/Center for Advanced Medicine
state: New York
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Columbus
country: United States
facility: Riverside Methodist Hospital
state: Ohio
city: Mentor
country: United States
facility: Lake University Ireland Cancer Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Tulsa
country: United States
facility: Oklahoma Cancer Specialists and Research Institute-Tulsa
state: Oklahoma
city: Abington
country: United States
facility: Abington Memorial Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Providence
country: United States
facility: Women and Infants Hospital
state: Rhode Island
city: Austin
country: United States
facility: University Medical Center Brackenridge
state: Texas
city: Dallas
country: United States
facility: Parkland Memorial Hospital
state: Texas
city: Dallas
country: United States
facility: Zale Lipshy University Hospital
state: Texas
city: Dallas
country: United States
facility: Clements University Hospital
state: Texas
city: Dallas
country: United States
facility: UT Southwestern/Simmons Cancer Center-Dallas
state: Texas
city: Temple
country: United States
facility: Scott and White Memorial Hospital
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University/Massey Cancer Center
state: Virginia
city: Bellingham
country: United States
facility: PeaceHealth Medical Group PC
state: Washington
city: Bremerton
country: United States
facility: Harrison HealthPartners Hematology and Oncology-Bremerton
state: Washington
city: Bremerton
country: United States
facility: Harrison Medical Center
state: Washington
city: Everett
country: United States
facility: Providence Regional Cancer Partnership
state: Washington
city: Mount Vernon
country: United States
facility: Skagit Valley Hospital Regional Cancer Care Center
state: Washington
city: Poulsbo
country: United States
facility: Harrison HealthPartners Hematology and Oncology-Poulsbo
state: Washington
city: Seattle
country: United States
facility: Pacific Gynecology Specialists
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Seattle
country: United States
facility: Group Health Cooperative-Seattle
state: Washington
city: Seattle
country: United States
facility: Swedish Medical Center-First Hill
state: Washington
city: Seattle
country: United States
facility: Northwest Hospital
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Sequim
country: United States
facility: Olympic Medical Cancer Care Center
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest - Spokane South
state: Washington
city: Spokane
country: United States
facility: Rockwood Cancer Treatment Center-DHEC-Downtown
state: Washington
city: Tacoma
country: United States
facility: MultiCare Tacoma General Hospital
state: Washington
city: Tacoma
country: United States
facility: Saint Joseph Medical Center
state: Washington
city: Walla Walla
country: United States
facility: Providence Saint Mary Regional Cancer Center
state: Washington
city: Wenatchee
country: United States
facility: Wenatchee Valley Hospital and Clinics
state: Washington
city: Mukwonago
country: United States
facility: D N Greenwald Center
state: Wisconsin
city: Oconomowoc
country: United States
facility: Oconomowoc Memorial Hospital-ProHealth Care Inc
state: Wisconsin
city: Waukesha
country: United States
facility: Waukesha Memorial Hospital
state: Wisconsin
Study officials:
affiliation: NRG Oncology
name: Charles Kunos
role: PRINCIPAL_INVESTIGATOR
References: