Trial record 1 of 1 for:    NCT01281150
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Veliparib in Combination With Carboplatin and Paclitaxel in Treating Patients With Locally Advanced or Metastatic Solid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01281150
First received: January 20, 2011
Last updated: July 16, 2014
Last verified: May 2014
  Purpose

This phase I clinical trial studies the side effects and the best dose of veliparib when given together with carboplatin and paclitaxel in treating patients with locally advanced or metastatic solid tumors. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by blocking them from dividing. Giving veliparib with carboplatin and paclitaxel may work better in treating patients with solid tumors.


Condition Intervention Phase
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
Drug: veliparib
Drug: paclitaxel
Drug: carboplatin
Other: pharmacological study
Other: laboratory biomarker analysis
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 ABT-888 (Veliparib) in Combination With Weekly Carboplatin and Paclitaxel in Advanced Solid Tumors

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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 National Cancer Institute (NCI) CTCAE v. 4.0 [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Incidence of adverse events as graded by the NCI CTCAE v. 4.0 [ Time Frame: Up to 4 weeks 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.

  • Grade >= 3 non-hematological or any grade 5 DLTs as graded by the NCI CTCAE v. 4.0 [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
    Statistics on the number of cycles received by patients and any dose reductions will be tabulated.

  • Response complete response [Cr], partial response [PR], and stable disease [SD]) using the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) [ Time Frame: Up to 4 weeks post-treatment ] [ Designated as safety issue: No ]
    CR, PR, and incidence of SD will be tabulated by disease diagnosis and by dose level.

  • Plasma concentration of carboplatin, paclitaxel, and veliparib using liquid chromatography-mass spectrometry (LC-MS) assay and spectrometry assay [ Time Frame: Baseline, at 30 minutes and at 1, 2, 4, and 8 hours on day 3 of course 1 ] [ Designated as safety issue: No ]
  • Change in PAR and g-H2AX in tumor tissue [ Time Frame: Baseline to day 4 of course 2 ] [ Designated as safety issue: No ]
    Assessed with Wilcoxon signed rank tests.

  • Change in BRCA protein levels by immunohistochemistry [ Time Frame: Baseline to day 4 of course 2 ] [ Designated as safety issue: No ]
    Calculated and compared using the Wilcoxon rank sum test.


Estimated Enrollment: 36
Study Start Date: January 2011
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (veliparib, paclitaxel, carboplatin)

DOSE-ESCALATION: Patients receive veliparib 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.

Drug: veliparib
Given PO
Other Name: ABT-888
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVE:

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

SECONDARY OBJECTIVES:

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 version 4.0 (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 poly (adenosine diphosphate [ADP]-ribose) polymerase (PAR) in tumor specimens when available, assessment of deoxyribonucleic acid (DNA) damage as measured by gamma H2A histone family, member X (g-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 breast cancer, early onset (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.

  Eligibility

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

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 human epidermal growth receptor -2 (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 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 must not have received chemotherapy within 4 weeks of starting study (or 6 weeks if prior treatment was with carmustine [BCNU] or mitomycin C)
    • Patients must not have received radiation within 2 weeks of starting study
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS)< 2 (Karnofsky > 60%)
  • Life expectancy > 2 months
  • Absolute neutrophil count (ANC) >= 1,500/mcL
  • Platelet count >= 100,000/mcL
  • Total bilirubin =< 1.5 times upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 times ULN
  • Creatinine normal within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73m^2 for patients with creatinine levels above institutional normal
  • Must able to swallow pills
  • Pregnant women are excluded from this study

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

    • Have accessible tumors
    • Not be on therapeutic anticoagulation
    • Have signed informed consent form

Exclusion Criteria:

  • Patients who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) or radiotherapy within 2 weeks (4 weeks for central nervous system [CNS] metastases) 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
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to veliparib or other agents used in study
  • 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
  • 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
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with veliparib
  • Active seizure or history of seizure disorder
  • 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
  • Patients who undergo biopsy as part of the study in the expanded dose cohort should not be on anti-coagulants or have a pre-existing coagulopathy
  • Peripheral neuropathy of severity greater than grade 1
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01281150

Locations
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         
Magee-Womens Hospital of UPMC Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Shannon Pulhalla    412-641-5792    puhallasl@upmc.edu   
Principal Investigator: Shannon Pulhalla         
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: NCT01281150     History of Changes
Other Study ID Numbers: NCI-2011-02490, NCI-2011-02490, CDR0000693333, 09-084, 8620, P30CA047904, U01CA099168
Study First Received: January 20, 2011
Last Updated: July 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Breast Neoplasms, Male
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on July 23, 2014