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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01540565
First received: February 22, 2012
Last updated: December 6, 2013
Last verified: December 2013
  Purpose

Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This phase II trial studies how well veliparib works in treating patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.


Condition Intervention Phase
BRCA1 Mutation Carrier
BRCA2 Mutation Carrier
Recurrent Fallopian Tube Cancer
Recurrent Ovarian Epithelial Cancer
Recurrent Primary Peritoneal Cavity Cancer
Drug: veliparib
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A PHASE II EVALUATION OF THE POLY (ADP-RIBOSE) POLYMERASE (PARP) -1 AND -2 INHIBITOR VELIPARIB (ABT-888) (IND #77840) (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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • The frequency of patients who have objective tumor response [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Frequency and severity of adverse effects as assessed by CTCAE v 4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Duration of PFS [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Will be characterized with Kaplan-Meier plots and estimates of the median time until death or progression.

  • Duration of OS [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Will be characterized with Kaplan-Meier plots and estimates of the median time until death or progression.

  • The proportion of patients who survive progression-free for at least 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Will be characterized with Kaplan-Meier plots and estimates of the median time until death or progression.


Estimated Enrollment: 51
Study Start Date: April 2012
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (veliparib)
Patients receive veliparib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: veliparib
Given PO
Other Name: ABT-888
Other: laboratory biomarker analysis
Correlative studies

Detailed 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).

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 DNA repair genes (e.g., BRCA1, Fanconi) and clinical characteristics, response, and patient outcome (PFS and OS).

OUTLINE: This is a multicenter study.

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.

Patients may undergo blood and tumor tissue sample collection for single nucleotide polymorphisms in DNA analysis.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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); 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 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 with both platinum-sensitive and platinum-resistant disease are eligible

    • Platinum-sensitive ovarian cancer is defined as patients who respond to platinum-based therapy (complete [CR]or partial response [PR]) 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 (CR or PR) and then progress/recur within 6 months of their last platinum dose (i.e., platinum-free interval is ≤ 6 months)
    • No patients with platinum-refractory disease

      • 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 PR to platinum-based chemotherapy (i.e., best response to platinum-based chemotherapy is stable disease)
  • No patients with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy, or any brain metastases
  • Patients who have received one prior cytotoxic regimen must have a Gynecologic Oncology Group (GOG) Performance Status of 0, 1, or 2; patients who have received two or three prior regimens must have a GOG Performance Status of 0 or 1
  • Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinaty tract infection [UTI])
  • 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 times institutional upper limit of normal (ULN)
  • Bilirubin less than or equal to 1.5 times ULN
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3 times ULN
  • Alkaline phosphatase less than or equal to 2.5 times 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
  • 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
  • No ability or unwillingness to swallow pills
  • No patients with clinical symptoms or signs of gastrointestinal obstruction and/or who require parenteral hydration or nutrition
  • No patients who are pregnant or nursing
  • Patients with seizures or history or seizures are ineligible
  • Patients with history or evidence upon physical examination of 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
  • See Disease Characteristics
  • Recovered from effects of recent surgery, radiotherapy, or chemotherapy
  • 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 the initiation of study treatment
  • Any prior radiation therapy must be discontinued at least four weeks prior to registration
  • 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
  • No patients who have had previous treatment with veliparib (ABT-888) or any other poly (ADP-ribose) polymerase (PARP) inhibitor (including olaparib)

    • Iniparib (BSI-201) cannot inhibit PARP1 at pharmacologically achievable concentrations, therefore prior iniparib therapy is allowed
  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01540565

  Show 154 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Robert Coleman Gynecologic Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01540565     History of Changes
Other Study ID Numbers: NCI-2012-00684, NCI-2012-00684, GOG-0280, CDR0000726699, GOG-0280, GOG-0280, U10CA027469
Study First Received: February 22, 2012
Last Updated: December 6, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Peritoneal Neoplasms
Fallopian Tube Neoplasms
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Abdominal Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Fallopian Tube Diseases
Adnexal Diseases
Genital Diseases, Female
Neoplasms by Histologic Type
Endocrine Gland Neoplasms
Ovarian Diseases
Endocrine System Diseases
Gonadal Disorders

ClinicalTrials.gov processed this record on April 15, 2014