Trial record 1 of 1 for:    NCT00892736
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Veliparib in Treating Patients With Malignant Solid Tumors That Did Not Respond to Previous Therapy

This study is currently recruiting participants.
Verified April 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00892736
First received: May 1, 2009
Last updated: April 9, 2014
Last verified: April 2014
  Purpose

This phase I trial studies the side effects and best dose of veliparib in treating patients with malignant solid tumors that did not respond to previous therapy. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.


Condition Intervention Phase
BRCA1 Mutation Carrier
BRCA2 Mutation Carrier
Estrogen Receptor-negative Breast Cancer
HER2-negative Breast Cancer
Hereditary Breast/Ovarian Cancer (BRCA1, BRCA2)
Male Breast Cancer
Progesterone Receptor-negative Breast Cancer
Recurrent Breast Cancer
Recurrent Fallopian Tube Cancer
Recurrent Ovarian Epithelial Cancer
Recurrent Pancreatic Cancer
Recurrent Primary Peritoneal Cavity Cancer
Recurrent Prostate Cancer
Triple-negative Breast Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: veliparib
Other: diagnostic laboratory biomarker analysis
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study of Chronically-Dosed, Single-Agent ABT-888 in Patients With Either BRCA 1/2 -Mutated Cancer; Platinum-Refractory Ovarian, Fallopian Tube, or Primary Peritoneal Cancer; or Basal-Like Breast Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • MTD, DLT, recommended phase II dose of chronically dosed single-agent veliparib in patients with either a refractory BRCA 1/2- mutated solid cancer; platinum- refractory ovarian, fallopian tube, or primary peritoneal cancer; or basal-like breast cancer [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Toxicity as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 [ Time Frame: Up to 30 days post-treatment ] [ Designated as safety issue: Yes ]
    The maximum grade of toxicity for each category of interest will be recorded for each patient and the summary results will be tabulated by category and grade. All DLTs and other serious (Grade 3 or greater) will be described on a patient-by-patient basis; descriptions will include dose level and any relevant baseline data. Statistics on the number of cycles received by patients and any dose reductions will be tabulated.

  • Response (complete response, partial response, stable disease) evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to 4 weeks post-treatment ] [ Designated as safety issue: No ]
    Will be tabulated by disease diagnosis and by dose level.

  • Pharmacokinetics [ Time Frame: Prior to taking veliparib on day 1, 4, and 15 then 30 minutes, 1 hour, 1½, 2, 3, 4, 6, and 8 hours after taking veliparib on day 1 and 15, and 24 hours after taking day 1and day 15 doses of veliparib ] [ Designated as safety issue: No ]
  • Changes in PAR and γ-H2AX in peripheral blood mononuclear cells [ Time Frame: Baseline to 4 weeks post-treatment ] [ Designated as safety issue: No ]
    Will be assessed with Wilcoxon signed rank tests. There will also be measurements of BRCA 1/2 expression in tumor blocks from patients with and without documented BRCA 1/2 mutations (i.e. platinum-refractory ovarian, fallopian tube, or primary peritoneal cancer and basal-like breast cancer); comparisons of the expression levels in the two groups of patients will be made with Wilcoxon tests.


Estimated Enrollment: 120
Study Start Date: April 2009
Estimated Primary Completion Date: June 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.

NOTE: *Patients receive veliparib once on day 1 of course 1 for pharmacokinetic and pharmacodynamic studies.

Blood samples are collected periodically for pharmacokinetic and pharmacodynamic studies. Samples are analyzed for plasma concentrations of veliparib by LC-MS; PARP inhibition levels; and γ-H2AX. Skin and hair samples may also be collected.

Drug: veliparib
Given PO
Other Name: ABT-888
Other: diagnostic laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To establish the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), and recommended phase II dose of chronically dosed single-agent ABT-888 (veliparib) in patients with either a refractory BRCA 1/2- mutated solid cancer; platinum- refractory ovarian, fallopian tube, or primary peritoneal cancer; or basal-like breast cancer

SECONDARY OBJECTIVES:

I. To establish the safety and tolerability of single-agent ABT-888 in the above patient population. A dose expansion at the recommended phase II dose will be performed in 6-12 evaluable patients with germline BRCA mutations.

II. To determine the effects of ABT-888 treatment on the level of poly ADP-ribose polymerase (PARP) inhibition and deoxyribonucleic acid (DNA) damage in peripheral blood mononuclear cells (PBMCs) and tumor samples or cells in malignant ascitic fluid III. To determine the pharmacokinetics (PK) of chronically dosed ABT-888. IV. To document any evidence of anti-tumor response.

OUTLINE: This is a multicenter study. This is a dose-escalation 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.

NOTE: *Patients receive veliparib once on day 1 of course 1 for pharmacokinetic and pharmacodynamic studies.

Blood samples are collected periodically for pharmacokinetic and pharmacodynamic studies. Samples are analyzed for plasma concentrations of veliparib by Liquid chromatography-mass spectrometry (LC-MS); PARP inhibition levels; and γ-H2AX. Skin and hair samples may also be collected.

After completion of study therapy, patients are followed for 4 weeks.

  Eligibility

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

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed solid tumors that fulfill at least one of the following 3 criteria:

    • Have a documented BRCA1/2 mutation and a BRCA related malignancy (primarily breast or ovarian cancers, but also may include prostate or pancreatic cancers); NOTE: Patients enrolled under the Dose Expansion Phase must have a documented BRCA 1/2 mutation; or
    • Platinum-refractory ovarian, fallopian tube, or primary peritoneal cancer or
    • Basal-like breast cancer
    • Whose disease has progressed following standard therapy or who have no acceptable standard treatment options
  • All patients without a known, documented BRCA mutation from Myriad Genetic Laboratories must have a probability of harboring a BRCA gene mutation assessed by BRCAPRO computer program

    • All patients in whom the probability of having a genetic mutation is >= 20% must have formal BRCA testing done through Myriad Genetic Laboratories in order to participate in the study
    • Although various research based tests have been developed to detect BRCA mutations, due to the fact that these are not Food and Drug Administration (FDA) or Clinical Laboratory Improvement Amendments (CLIA) approved and therefore not reportable to patients, if a patient has diagnosis of a BRAC mutation based on a non-Myriad test, then they must undergo Myriad BRCA gene sequencing to be eligible
    • Patients are eligible whether they have a known deleterious BRCA 1 or 2 mutation or a mutation of uncertain significance
    • If a patient refuses BRCA testing, then they are ineligible for the study
  • Platinum-refractory is defined as progression or recurrence within 6 months of initial platinum response; platinum-resistant is defined as having no prior response to platinum (i.e. evidence of progression within 2-3 cycles of beginning initial platinum-based treatment) and platinum-resistant patients are excluded; the only platinum-sensitive patients that are eligible are those with known BRCA mutations
  • Basal-like breast cancer will be defined as estrogen and progesterone receptor negative, human epidermal growth factor receptor 2 (HER2) negative, and/or having expression profile of epidermal growth factor receptor (EGFR) and cytokeratins 5/6, consistent with basal phenotype; breast cancer patients with "triple-negative" phenotype (negative hormone and HER2 receptors) are eligible to participate in this trial; patients who are only known to be "triple-negative" but unknown basal phenotype will have their tumor blocks assessed for basal markers
  • For subjects enrolled under the Dose Escalation Phase: Enrolled patients without a known BRCA mutation must have archived tumor tissue available for assessment of BRCA 1/2 protein expression by immunohistochemistry, as well as other correlative studies; it is optional for patients with a known BRCA mutation to provide archived tissue for correlative studies
  • For subjects enrolled under the Dose Expansion Phase: All patients enrolled during the Dose Expansion Phase (for which a tissue biopsy is mandatory) must have a known BRCA mutation and must agree to collection or archival tumor tissue, if available
  • There are no limitations on the amount of prior therapies received; however, no major surgery, radiation or chemotherapy within four weeks prior to study enrollment except for mitomycin C and nitrosoureas, in which case it is 6 weeks; patients must be recovered from toxicities of prior therapies to at least eligibility levels
  • Eastern Cooperative Oncology Group (ECOG) performance status < 2 (Karnofsky > 60%)
  • Life expectancy of greater than 3 months
  • Transaminases =< 2.5 times upper limit of normal (ULN)
  • Bilirubin =< 2.0 mg/dL
  • Creatinine =< ULN or a creatinine clearance > 50 ml/minute (calculated by Cockroft-Gault formula) if creatinine > ULN
  • Neutrophils >= 1500/ µL
  • Platelets >= 100,000/µL
  • 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
  • Ability to understand and the willingness to sign a written informed consent document
  • Ability to swallow pills
  • Patients with central nervous system (CNS) metastases must be stable after therapy for CNS metastases (such as surgery, radiotherapy or stereotactic radiosurgery) for > 3 months and must be off steroid treatment prior to study enrollment and must have a life expectancy of 3 months or greater to be eligible
  • Patients with BRCA mutations who are enrolled in the 6-12 patient expansion group at dose level VIII (400 mg BID) must agree to tumor biopsies; therefore patients enrolled in this cohort should have tumors easily accessible for biopsies with low likelihood of complication and these patients should not be on therapeutic doses of anticoagulation
  • Patients with BRCA mutations who are enrolled in the 6-12 patient expansion group at dose level VIII (400 mg BID) must agree to collection of archival tissue, if available. If not available, patient may still be enrolled as long as the patient consents to the mandatory fresh tumor tissue biopsies

Exclusion Criteria:

  • Patients who have had chemotherapy, hormone therapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients may not be receiving any other investigational agents

    • Patients with prostate cancer must continue ongoing luteinizing-hormone-releasing hormone (LhRH) agonist therapy and discontinue antiandrogens at least 6 weeks (for bicalutamide) or 4 weeks (flutamide) prior to study entry; patients with bone metastases or hypercalcemia who began intravenous bisphosphonate treatment prior to study entry may continue this treatment
  • Patients with CNS metastases must be stable after therapy for CNS metastases (such as surgery, radiotherapy or stereotactic radiosurgery) for > 3 months and must be off steroid treatment prior to study enrollment and must have a life expectancy secondary to that of 3 months or greater to be eligible
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Human immunodeficiency virus (HIV) infected patients on protease inhibitors are ineligible due to potential for drug-drug interactions and increased drug effects; HIV infected patients with adequate CD4 counts (> 500) and not on protease inhibitors are eligible
  • Pregnant women are excluded
  • Active seizure or history of seizure disorder
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00892736

Locations
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Robert J. Morgan    626-256-4673    rmorgan@coh.org   
Principal Investigator: Robert J. Morgan         
University of Southern California/Norris Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Agustin A. Garcia    323-865-0832    aagarcia@usc.edu   
Principal Investigator: Agustin A. Garcia         
University of California at Davis Cancer Center Recruiting
Sacramento, California, United States, 95817
Contact: David R. Gandara    916-734-3772    david.gandara@ucdmc.ucdavis.edu   
Principal Investigator: David R. Gandara         
City of Hope South Pasadena Recruiting
South Pasadena, California, United States, 91030
Contact: Stephen C. Koehler    626-396-2900    Skoehler@cohmg.com   
Principal Investigator: Stephen C. Koehler         
United States, New Jersey
Cancer Institute of New Jersey Recruiting
New Brunswick, New Jersey, United States, 08903
Contact: Antoinette R. Tan    732-235-6777    tanan@umdnj.edu   
Principal Investigator: Antoinette R. Tan         
United States, Pennsylvania
Penn State Milton S Hershey Medical Center Recruiting
Hershey, Pennsylvania, United States, 17033-0850
Contact: Chandra P. Belani    717-531-1078    cbelani@psu.edu   
Principal Investigator: Chandra P. Belani         
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Shannon L. Puhalla    412-641-5792    puhallasl@upmc.edu   
Principal Investigator: Shannon L. Puhalla         
Sponsors and Collaborators
Investigators
Principal Investigator: Shannon Puhalla University of Pittsburgh
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00892736     History of Changes
Other Study ID Numbers: NCI-2011-01472, NCI-2011-01472, CINJ-050810, CDR0000641433, U01CA062505, UPCI 08-121, U01CA099168, 08-121, 8282, U01CA062505, P30CA047904, U01CA099168
Study First Received: May 1, 2009
Last Updated: April 9, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on April 16, 2014