Veliparib in Treating Patients With Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Recurrent Ovarian Carcinoma Clinical Trial

Official title:

A Phase II Evaluation of the Poly (ADP-Ribose) Polymerase (PARP)-1 and -2 Inhibitor Veliparib (ABT-888) (NSC#737664) in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients Who Carry a Germline BRCA1 or BRCA2 Mutation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01540565
• Other study ID #: NCI-2012-00684
• Secondary ID: NCI-2012-00684S1
• Status: Completed
• Phase: Phase 2
• Start date: April 9, 2012
• Est. completion date: January 27, 2018

Study information

• Verified date: July 2019
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial studies how well veliparib works in treating patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer that has come back or does not respond to treatment. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Description:

PRIMARY OBJECTIVES:

I. To estimate the proportion of patients who have objective tumor response (complete or partial).

II. To determine the frequency and severity of adverse events associated with treatment with veliparib (ABT-888) as assessed by the Active Version of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

SECONDARY OBJECTIVES:

I. To determine the duration of progression-free survival (PFS) and overall survival (OS).

II. To determine the proportion of patients who survive progression-free for at least 6 months.

TERTIARY OBJECTIVES:

I. To explore the association between single nucleotide polymorphisms (SNPs) in deoxyribonucleic acid (DNA) repair genes (e.g., breast cancer [BRCA]1, Fanconi) and clinical characteristics, response, and patient outcome (PFS and OS).

OUTLINE:

Patients receive veliparib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: January 27, 2018
• Est. primary completion date: January 27, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma AND carry a germline mutation in BRCA1 or BRCA2 (confirmation required via Myriad test report); histologic documentation of the original primary tumor is required via the pathology report

• All patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors(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; 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 who have received one prior cytotoxic regimen must have a Gynecological Oncology Group (GOG) performance status of 0, 1, or 2

• Patients who have received two or three prior cytotoxic regimens must have a GOG performance status of 0 or 1

• Recovery from effects of recent surgery, radiotherapy, or chemotherapy

• 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

• Any other prior therapy directed at the malignant tumor, including chemotherapy, biologic/targeted (non-cytotoxic) agents and immunologic agents, must be discontinued at least three weeks prior to registration; patients receiving nitrosoureas or mitomycin C must discontinue 6 weeks prior to registration

• Any prior radiation therapy must be discontinued at least four weeks prior to registration

• Prior therapy

• Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound; this initial treatment may have included intraperitoneal therapy, consolidation, biologic/targeted (non-cytotoxic) agents or extended therapy administered after surgical or non-surgical assessment

• Patients are allowed to receive, but are not required to receive, two additional cytotoxic regimens for management of recurrent or persistent disease

• Patients are allowed to receive, but are not required to receive, biologic/targeted (non-cytotoxic) therapy for management of recurrent or persistent disease; patients are allowed to receive, but are not required to receive, biologic/targeted (non-cytotoxic) therapy as part of their primary treatment regimen

• Patients with both platinum-sensitive and platinum-resistant disease are eligible; patients with platinum-refractory disease are NOT eligible

• Definitions:

• Platinum sensitive ovarian cancer is defined as patients who respond to platinum-based therapy (complete or partial) and then progress/recur more than 6 months after their last platinum dose (i.e., platinum-free interval is > 6 months)

• Platinum resistant ovarian cancer is defined as patients who respond to platinum-based therapy (complete or partial) and then progress/recur within 6 months of their last platinum dose (i.e., platinum-free interval is =< 6 months)

• Platinum refractory ovarian cancer is defined as patients who have progression of disease while receiving platinum-based chemotherapy or who fail to achieve at least a partial response to platinum-based chemotherapy (i.e., best response to platinum-based chemotherapy is stable disease)

• 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

• 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

Exclusion Criteria:

• Patients who have had previous treatment with veliparib (ABT-888) or any other poly (adenosine diphosphate [ADP]-ribose) polymerase 1 (PARP) inhibitor (including olaparib); note: Iniparib (BSI-201) cannot inhibit PARP1 at pharmacologically achievable concentrations, therefore prior iniparib therapy is allowed

• 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 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 ovarian, fallopian tube, or primary peritoneal 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 ovarian, fallopian tube, or primary peritoneal 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 with seizures or history or 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

• Inability or unwillingness to swallow pills

• Patients with clinical symptoms or signs of gastrointestinal obstruction and/or who require parenteral hydration or nutrition

• Patients who are pregnant or nursing

Related Conditions & MeSH terms

• BRCA1 Mutation Carrier
• BRCA2 Mutation Carrier
• Carcinoma
• Carcinoma, Ovarian Epithelial
• Fallopian Tube Neoplasms
• Ovarian Epithelial Tumor
• Ovarian Neoplasms
• Recurrent Fallopian Tube Carcinoma
• Recurrent Ovarian Carcinoma
• Recurrent Primary Peritoneal Carcinoma

Intervention

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Veliparib
Given PO

Locations

Country	Name	City	State
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	Summa Akron City Hospital/Cooper Cancer Center	Akron	Ohio
United States	McFarland Clinic PC - Ames	Ames	Iowa
United States	AnMed Health Cancer Center	Anderson	South Carolina
United States	Hope Women's Cancer Centers-Asheville	Asheville	North Carolina
United States	Northside Hospital	Atlanta	Georgia
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	PeaceHealth Medical Group PC	Bellingham	Washington
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Harrison Medical Center	Bremerton	Washington
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	University of Vermont Medical Center	Burlington	Vermont
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	John Muir Medical Center-Concord Campus	Concord	California
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Henry Ford Hospital	Detroit	Michigan
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	Duke University Medical Center	Durham	North Carolina
United States	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin
United States	Fairview-Southdale Hospital	Edina	Minnesota
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Union Hospital of Cecil County	Elkton	Maryland
United States	Rocky Mountain Gynecologic Oncology PC	Englewood	Colorado
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Baylor All Saints Medical Center at Fort Worth	Fort Worth	Texas
United States	Unity Hospital	Fridley	Minnesota
United States	Northeast Georgia Medical Center-Gainesville	Gainesville	Georgia
United States	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	Greenville Health System Cancer Institute-Eastside	Greenville	South Carolina
United States	Greenville Health System Cancer Institute-Faris	Greenville	South Carolina
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Sudarshan K Sharma MD Limted-Gynecologic Oncology	Hinsdale	Illinois
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	M D Anderson Cancer Center	Houston	Texas
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Saint Vincent Hospital and Health Care Center	Indianapolis	Indiana
United States	Cancer Center of Kansas-Kingman	Kingman	Kansas
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Women's Cancer Center of Nevada	Las Vegas	Nevada
United States	Beebe Medical Center	Lewes	Delaware
United States	Cancer Center of Kansas-Liberal	Liberal	Kansas
United States	Norton Hospital Pavilion and Medical Campus	Louisville	Kentucky
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Holy Family Memorial Hospital	Manitowoc	Wisconsin
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Bay Area Medical Center	Marinette	Wisconsin
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	Loyola University Medical Center	Maywood	Illinois
United States	Lake University Ireland Cancer Center	Mentor	Ohio
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Skagit Valley Hospital Regional Cancer Care Center	Mount Vernon	Washington
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	Yale University	New Haven	Connecticut
United States	New Ulm Medical Center	New Ulm	Minnesota
United States	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Gynecologic Oncology Associates-Newport Beach	Newport Beach	California
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	Florida Hospital Orlando	Orlando	Florida
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Saint Joseph's Hospital and Medical Center	Phoenix	Arizona
United States	Maine Medical Center-Bramhall Campus	Portland	Maine
United States	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington
United States	Cancer Center of Kansas - Pratt	Pratt	Kansas
United States	Women and Infants Hospital	Providence	Rhode Island
United States	Ascension Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Marshfield Clinic-Rice Lake Center	Rice Lake	Wisconsin
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Rutherford Hospital	Rutherfordton	North Carolina
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	UCSF Medical Center-Mount Zion	San Francisco	California
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Kaiser Permanente Washington	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	Greenville Health System Cancer Institute-Seneca	Seneca	South Carolina
United States	Olympic Medical Cancer Care Center	Sequim	Washington
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Greenville Health System Cancer Institute-Spartanburg	Spartanburg	South Carolina
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	Ascension Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Lakeview Hospital	Stillwater	Minnesota
United States	MultiCare Tacoma General Hospital	Tacoma	Washington
United States	Saint Joseph Medical Center	Tacoma	Washington
United States	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington
United States	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington
United States	Aurora West Allis Medical Center	West Allis	Wisconsin
United States	Marshfield Clinic - Weston Center	Weston	Wisconsin
United States	Associates In Womens Health	Wichita	Kansas
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Via Christi Regional Medical Center	Wichita	Kansas
United States	Wichita NCI Community Oncology Research Program	Wichita	Kansas
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Southeast Clinical Oncology Research (SCOR) Consortium NCORP	Winston-Salem	North Carolina
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Lankenau Medical Center	Wynnewood	Pennsylvania
United States	Main Line Health NCORP	Wynnewood	Pennsylvania

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
Other	SNPs With DNA Repair Genes, Tumor Response, PFS, OS, and Patient Demographics (e.g. Age, Race, Tumor Grade)	If the clinical trial goes to the second stage and there is sufficient variability in the SNPs, then patients can be categorized by the nature of their SNPs and assessed for prognostic value through survival analysis (e.g. log-rank tests and Cox proportional hazards modeling). If the variability in SNPs is relatively low, assessment of prognostic value can be conducted with odds ratios of patients responding or surviving progression-free for at least 6 months. These techniques will use exact methods such as Fisher's exact test.	Baseline
Other	BRCA Mutation in Primary Tumor Tissue	BRCA mutational status will be tabulated against the germline mutation to see what proportion of patients have a mutation reversal within the tumor and whether such reversals can explain resistance to the regimen under study.	Baseline
Primary	Proportion of Patients With Complete and Partial Tumor Response	Patients with complete and partial tumor response by RECIST V1.1 (per response evaluation criteria in Solid Tumors Criteria (RECIST V1.1) for target lesions and assessed by MRI (CT scan): Complete Response (CR), disappearance of all target lesions (confirmed at >= 4 weeks); Partial Response (PR) >= 30% decrease in the sum of the longest diameter of target lesions (confirmed at >= 4 weeks); Overall Response = CR + PR.	CT scan/MRI if used to follow lesion for measurable disease every other cycle for the first 6 months, then every 3 months until progression. Repeat at other times if clinically indicated.Responses require confirmation at >= 4 wks from first documentation.
Primary	Proportion of Patients With Adverse Events as Assessed by CTCAE v4.0	Patients with grade 3 or greater Adverse Events (AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported.	After every cycle while on study therapy. Followed for late adverse events up to 30 days after completing therapy.
Secondary	Duration of PFS	The time from randomization until disease progression, death, or date of last contact. Endpoints are progression or death. Patients who are not observed with an endpoint are censored. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions (and >= 5 mm increase of target lesions), or a measurable increase in a non-target lesion, or the appearance of new lesions.	CT scan/MRI if used to follow lesion for measurable disease every other cycle for the first 6 months, then every 3 months until progression. Patients who begin subsequent therapy without progression will be monitored for PFS for 5 years.
Secondary	Duration of OS	Overall survival	Every cycle while patient is receiving protocol therapy. Patients will be monitored for survival after going off therapy for a 5 year period, every 3 months for the first 2 years, then every 6 months for the last 3 years.
Secondary	The Proportion of Patients Who Survive Progression-free for at Least 6 Months	This outcome captures whether or not the patient survived progression-free for at least 6 months, and is displayed as a proportion.	6 months