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A Phase 1 Study of ABT-888 (Veliparib) in Combination With Weekly Carboplatin and Paclitaxel in Advanced Solid Tumors

Phase 1
18 Years
Open (Enrolling)
Estrogen Receptor-negative Breast Cancer, Estrogen Receptor-positive Breast Cancer, HER2-negative Breast Cancer, Male Breast Cancer, Progesterone Receptor-negative Breast Cancer, Recurrent Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer, Stage IV Breast Cancer, Triple-negative Breast Cancer, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase 1 Study of ABT-888 (Veliparib) in Combination With Weekly Carboplatin and Paclitaxel in Advanced Solid Tumors


I. To determine the maximum-tolerated dose (MTD) of the combination of weekly carboplatin,
paclitaxel, and veliparib.


I. To assess the safety, tolerability, and MTD of the combination of weekly carboplatin,
paclitaxel, and veliparib.

II. To assess the safety and toxicity of this combination as determined by the Common
Terminology Criteria for Adverse Events (CTCAE) v. 4.0 and to determine the dose-limiting
toxicity (DLT).

III. To determine the pharmacokinetic and pharmacodynamic effects of this combination,
including determinations of PAR in tumor specimens when available, assessment of DNA damage
as measured by gamma H2AX in skin biopsies and tumor specimens will be obtained.

IV. To assess characteristics of primary tumor specimens that may contribute to efficacy of
this combination including BRCA by immunohistochemistry, gene analysis of PARP 1, PARP 2,
BRCA, and triple negative and homologous recombination repair (HRR) deficiency gene
expression signatures.

V. To document any anti-tumor response.

OUTLINE: This is a dose-escalation study of veliparib.

DOSE-ESCALATION: Patients receive veliparib orally (PO) twice daily (BID) on days 1-5, 8-12,
and 15-19 and paclitaxel IV over 1 hour and carboplatin IV over 30 minutes in course 1 and 3
hours in subsequent courses on days 3, 10, and 17. After 4 courses, patients receive
paclitaxel and carboplatin on days 3 and 10 only. Courses repeat every 21 days in the
absence of disease progression or unacceptable toxicity. (Completed as of 12/2012)

EXPANSION COHORT: Patients receive veliparib PO BID on days 1-21 and paclitaxel IV over 1
hour and carboplatin IV over 3 hours on days 3 and 10. Courses repeat every 21 days in the
absence of disease progression or unacceptable toxicity.

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

Inclusion Criteria:

- Histologically or cytologically confirmed solid tumor that has evidence of metastatic
spread (stage IV) or is locally advanced and unresectable

- Patients with breast cancer may have estrogen receptor positive or negative (ER+
or ER-) disease

- Patients with breast cancer may not be HER2-positive ( 3+), or fluorescent in
situ hybridization (FISH) ratio > 2.2

- Patients in the biopsy expansion cohort must have "triple negative" breast
cancer defined as:

- Estrogen receptor staining < 10%; progesterone receptor staining <10%; Her
2 < 2.2 by FISH, or immunohistochemistry (IHC) 0-2+

- Patients enrolled in the expanded cohort with mandatory biopsies must:

- Have accessible tumors

- Not be on therapeutic anticoagulation

- Have signed informed consent form

- Patients may have been previously treated

- In the dose escalation cohort, there is no limit to prior therapies

- In the expansion cohort, patients may have only had 1-3 prior regimens for
metastatic disease

- Patients may have received prior carboplatin, paclitaxel, or poly (ADP-ribose)
polymerase (PARP) inhibitor therapy as part of their previous treatment regimens

- However, patients may NOT have received prior therapy with paclitaxel,
carboplatin, and PARP inhibitor in combination

- 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

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 (Karnofsky PS

- Life expectancy > 2 months

- Absolute neutrophil count (ANC) >= 1,500/mm^3

- Platelet count >= 100,000/mm^3

- Total bilirubin =< 1.5 times upper limit of normal (ULN)

- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 times ULN

- Creatinine normal OR creatinine clearance >= 60 mL/min

- Able to swallow pills

- Not pregnant or nursing

- Negative pregnancy test

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal, barrier method of birth control, or abstinence) prior to study entry and
for the duration of study participation

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to veliparib or other agents used in study

- No 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

- No active seizure or history of seizure disorder

- No peripheral neuropathy of severity greater than grade 1

- More than 4 weeks since prior chemotherapy (6 weeks for carmustine [BCNU],
nitrosoureas, or mitomycin C) and recovered

- More than 2 weeks since prior radiotherapy

- Concurrent treatment with bisphosphonates, or other bone anti-resorptive agent such
as denosumab is allowed; concurrent treatment with hormonal therapy (tamoxifen,
ovarian suppression with gonadotropin-releasing hormone [GNRH] agonists, aromatase
inhibitors) or trastuzumab therapy is NOT allowed in breast cancer patients; prostate
cancer patients may continue GNRH agents

- No other concurrent investigational agents

Type of Study:


Study Design:

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

Outcome Measure:

MTD defined as the dose level one level below the lowest dose where greater than or equal to 2 patients experience a DLT assessed by NCI CTCAE v. 4.0

Outcome Time Frame:

24 days

Safety Issue:


Principal Investigator

Shannon Puhalla

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Pittsburgh


United States: Food and Drug Administration

Study ID:




Start Date:

January 2011

Completion Date:

Related Keywords:

  • Estrogen Receptor-negative Breast Cancer
  • Estrogen Receptor-positive Breast Cancer
  • HER2-negative Breast Cancer
  • Male Breast Cancer
  • Progesterone Receptor-negative Breast Cancer
  • Recurrent Breast Cancer
  • Stage IIIB Breast Cancer
  • Stage IIIC Breast Cancer
  • Stage IV Breast Cancer
  • Triple-negative Breast Cancer
  • Unspecified Adult Solid Tumor, Protocol Specific
  • Breast Neoplasms
  • Breast Neoplasms, Male
  • Neoplasms



Penn State Milton S Hershey Medical Center Hershey, Pennsylvania  17033
Magee-Womens Hospital - University of Pittsburgh Medical Center Pittsburgh, Pennsylvania  15213