Know Cancer

or
forgot password

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


Phase 1
18 Years
N/A
Open (Enrolling)
Both
BRCA1 Mutation Carrier, BRCA2 Mutation Carrier, Estrogen Receptor-negative Breast Cancer, Fallopian Tube Cancer, HER2-negative Breast Cancer, Hereditary Breast/Ovarian Cancer (BRCA1, BRCA2), Male Breast Cancer, Primary Peritoneal Cavity Cancer, Progesterone Receptor-negative Breast Cancer, Recurrent Breast Cancer, Recurrent Ovarian Epithelial Cancer, Recurrent Pancreatic Cancer, Recurrent Prostate Cancer, Triple-negative Breast Cancer, Unspecified Adult Solid Tumor, Protocol Specific

Thank you

Trial Information

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


PRIMARY OBJECTIVES:

I. To establish the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) 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
patients with germline BRCA mutations.

II. To determine the effects of ABT-888 treatment on the level of PARP inhibition and DNA
damage in 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.

Patients receive veliparib* orally (PO) daily 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.

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


Inclusion Criteria:



- Histologically or cytologically confirmed malignant solid tumor meeting ≥ 1 of the
following criteria:

- Documented BRCA1/2 mutation AND a BRCA-related malignancy (e.g., primarily
breast or ovarian cancer, but may include prostate or pancreatic cancer)

- Platinum-refractory ovarian, fallopian tube, or primary peritoneal cancer

- Platinum-refractory is defined as progression or recurrence within 6 months
of initial platinum response

- No platinum-resistant disease, defined as no prior response to
platinum-based therapy (i.e., evidence of progression within 2-3 courses of
beginning initial platinum-based therapy)

- Patients with platinum-sensitive disease must have known BRCA mutations

- Basal-like breast cancer, defined as estrogen and progesterone
receptor-negative, HER2-negative, and/or expression profile of EGFR and
cytokeratins 5/6 consistent with basal phenotype

- "Triple-negative" phenotype (i.e., negative hormone and HER2 receptors)
allowed

- Patients with known "triple-negative" phenotype but unknown basal
phenotype will have their tumor blocks assessed for basal markers

- Progressive disease after standard therapy OR no acceptable standard treatment
options available

- Patients without a known BRCA mutation must have archived tumor tissue samples
available for assessment of BRCA1/2 protein expression by immunohistochemistry

- Patients without a known, documented BRCA mutation from Myriad Genetic
Laboratories must have a probability of harboring a BRCA gene mutation as
assessed by BRCAPRO computer program

- Patients with a probability of harboring a BRCA gene mutation of ≥ 20% must
undergo formal BRCA testing by Myriad Genetic Laboratories

- Patients with a diagnosis of a BRCA mutation based on a non-Myriad test
must undergo Myriad BRCA gene sequencing

- Known deleterious BRCA1 or 2 mutation or a mutation of uncertain significance
allowed

- Patients enrolled on dose levels VI-IX must be willing to undergo skin biopsies and
hair sample collection before starting treatment and on day 4

- Patients who are receiving therapeutic doses of anticoagulation are exempt

- Patients with BRCA mutations who are enrolled in the 6-patient expansion group at the
MTD (or dose level IX) must agree to tumor biopsies

- Tumors must be easily accessible for biopsies with low likelihood of
complication

- Patients should not be on therapeutic doses of anticoagulation

- Patients with BRCA mutations who are enrolled in the 6-12 patient expansion group at
the MTD (or dose level IX) 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

- Hormone receptor status not specified

- Menopausal status not specified

- ECOG performance status (PS) 0-2 (Karnofsky PS 60-100%)

- Life expectancy > 3 months

- ANC ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Bilirubin ≤ 2.0 mg/dL

- Transaminases ≤ 2.5 times upper limit of normal

- Creatinine normal OR creatinine clearance > 50 mL/min

- Not pregnant or nursing

- Fertile patients must use effective contraception

- HIV infection allowed provided CD4 count > 500/mm³

- Able to swallow pills

- No concurrent uncontrolled illness including, but not limited to, any of the
following:

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Psychiatric illness or social situation that would limit compliance with study
requirements

- No concurrent protease inhibitors for patients with HIV infection

- Recovered from all prior therapy

- More than 4 weeks since prior major surgery, radiotherapy, or chemotherapy (6 weeks
for nitrosoureas or mitomycin C)

- At least 4 weeks since prior flutamide (6 weeks for bicalutamide) for prostate cancer

- Concurrent ongoing luteinizing hormone-releasing hormone agonist therapy for
prostate cancer required

- Concurrent IV bisphosphonates for bone metastases or hypercalcemia allowed provided
treatment was initiated prior to study entry

- No concurrent chemotherapy

- No other concurrent investigational agents

- No other concurrent anticancer therapy

- 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

- Active seizure or history of seizure disorder are excluded

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

28 days

Safety Issue:

Yes

Principal Investigator

Shannon Puhalla

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Pittsburgh

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2011-01472

NCT ID:

NCT00892736

Start Date:

April 2009

Completion Date:

Related Keywords:

  • brca1 Mutation Carrier
  • brca2 Mutation Carrier
  • Estrogen Receptor-negative Breast Cancer
  • Fallopian Tube Cancer
  • HER2-negative Breast Cancer
  • Hereditary Breast/Ovarian Cancer (brca1, brca2)
  • Male Breast Cancer
  • Primary Peritoneal Cavity Cancer
  • Progesterone Receptor-negative Breast Cancer
  • Recurrent Breast Cancer
  • Recurrent Ovarian Epithelial Cancer
  • Recurrent Pancreatic Cancer
  • Recurrent Prostate Cancer
  • Triple-negative Breast Cancer
  • Unspecified Adult Solid Tumor, Protocol Specific
  • Breast Neoplasms
  • Ovarian Neoplasms
  • Pancreatic Neoplasms
  • Prostatic Neoplasms
  • Peritoneal Neoplasms
  • Fallopian Tube Neoplasms
  • Breast Neoplasms, Male
  • Neoplasms, Glandular and Epithelial

Name

Location

Cancer Institute of New JerseyNew Brunswick, New Jersey  08901
City of HopeDuarte, California  91010
University of PittsburghPittsburgh, Pennsylvania  15261
UC Davis Comprehensive Cancer CenterSacramento, California  95817
University of Southern CaliforniaLos Angeles, California  90033
Penn State Milton S Hershey Medical CenterHershey, Pennsylvania  17033
City of Hope- South Pasadena Cancer CenterSouth Pasadena, California  91030