Carboplatin and Combination Chemotherapy With or Without Veliparib in Treating Patients With Stage IIB-IIIC Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Thomas Jefferson University
Sponsor:
Collaborator:
Susan G. Komen Breast Cancer Foundation
Information provided by (Responsible Party):
Thomas Jefferson University
ClinicalTrials.gov Identifier:
NCT01818063
First received: March 21, 2013
Last updated: May 13, 2014
Last verified: May 2014
  Purpose

This randomized phase II trial studies how well carboplatin and combination chemotherapy with or without veliparib works in treating patients with stage IIB-IIIC breast cancer. Drugs used in chemotherapy, such as paclitaxel, carboplatin, doxorubicin hydrochloride, and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving carboplatin and combination chemotherapy are more effective with or without veliparib is more effective in treating breast cancer.


Condition Intervention Phase
Estrogen Receptor-negative Breast Cancer
HER2-negative Breast Cancer
Progesterone Receptor-negative Breast Cancer
Stage II Breast Cancer
Stage IIIA Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Triple-negative Breast Cancer
Drug: Paclitaxel
Drug: Carboplatin
Drug: Doxorubicin
Drug: Cyclophosphamide
Drug: Veliparib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Adaptive, Randomized Phase II Trial to Determine Pathologic Complete Response With the Addition of Carboplatin With and Without Veliparib to Standard Chemotherapy in the Neoadjuvant Treatment of Triple-Negative Breast Cancer

Resource links provided by NLM:


Further study details as provided by Thomas Jefferson University:

Primary Outcome Measures:
  • Pathologic complete response (PCR) [ Time Frame: At the time of surgery ] [ Designated as safety issue: No ]
    PCR is defined as the absence of any residual invasive cancer on hematoxylin and eosin (H&E) evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes. The posterior distribution of the odds ratio will be used to assess whether carboplatin and/or carboplatin +veliparib in combination with paclitaxel has a higher PCR compared to each other and simulations will be used to compare to paclitaxel alone. A 95% credible region will be calculated for the odds ratio comparing the two combination treatments, the odds ratio comparing each treatment to paclitaxel alone, the PCR for each treatment regimen, for the difference in the PCR between each combination regimen, and the difference of each combination regimen to paclitaxel alone.


Secondary Outcome Measures:
  • Overall clinical response [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    The proportion of subjects with each category of overall clinical response will be summarized by presence of baseline measureable disease (i.e., complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD], unable to evaluate [UE], neurogenerative disease [ND]). Beta will be used as priors for combination regimens in calculating the posterior distribution of the PCR for each respective treatment group. Among subjects with measurable disease, a 95% credible region will be calculated for the odds ratio for each treatment combination relative to each other.

  • Relapse free survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Analyzed using Kaplan-Meier methods, stratified by study group, and the log rank test will be completed.


Estimated Enrollment: 80
Study Start Date: April 2013
Estimated Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 (paclitaxel, carboplatin)
Patients receive paclitaxel IV and carboplatin IV on day 1 (course 1 only) or day 2 (courses 2-12). Treatment repeats every 7 days for 12 courses in the absence of disease progression or unacceptable toxicity. Beginning 21 days after the last course, patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Drug: Paclitaxel
Given IV
Other Names:
  • Taxol
  • Abraxane
Drug: Carboplatin
Given IV
Other Names:
  • cis-Diammine(1,1-cyclobutanedicarboxylato)platinum(II)
  • Paraplatin
  • Paraplatin-AQ
Drug: Doxorubicin
Given IV
Other Names:
  • Adriamycin
  • hydroxydaunorubicin
  • Adriamycin PFS
  • Adriamycin RDF
  • Rubex
  • Doxil
Drug: Cyclophosphamide
Given IV
Other Names:
  • Endoxan
  • Cytoxan
  • Neosar
  • Procytox
  • Revimmune
  • cytophosphane
  • Lyophilizedcytoxan
Experimental: Arm 2 (veliparib, paclitaxel, carboplatin)
Patients receive veliparib PO BID on days 1-5. Patients also receive paclitaxel IV and carboplatin IV on day 3 (course 1 only) or day 4 (courses 2-12). Treatment repeats every 7 days for 12 courses in the absence of disease progression or unacceptable toxicity. Beginning 21 days after the last course, patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Drug: Paclitaxel
Given IV
Other Names:
  • Taxol
  • Abraxane
Drug: Carboplatin
Given IV
Other Names:
  • cis-Diammine(1,1-cyclobutanedicarboxylato)platinum(II)
  • Paraplatin
  • Paraplatin-AQ
Drug: Doxorubicin
Given IV
Other Names:
  • Adriamycin
  • hydroxydaunorubicin
  • Adriamycin PFS
  • Adriamycin RDF
  • Rubex
  • Doxil
Drug: Cyclophosphamide
Given IV
Other Names:
  • Endoxan
  • Cytoxan
  • Neosar
  • Procytox
  • Revimmune
  • cytophosphane
  • Lyophilizedcytoxan
Drug: Veliparib
Given PO
Other Name: ABT-888

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  1. Written informed consent must be obtained prior to any study-related procedures.
  2. Histologically confirmed adenocarcinoma of the breast with the following markers: Estrogen receptor negative (<1%), progesterone receptor negative (<1%), and Her-2/neu negative (Her-2/neu 0-1+ IHC or FISH ratio <1.8 or average HER2 gene copy number of <four signal/nucleus for test systems without internal control probe).
  3. Female ≥ 18 years old.
  4. Clinical stage IIA (T2N0), IIB (T2N1, T3N0) or stage IIIA (T1N2, T2N2, T3N1, T3N2), IIIB, or IIIC breast cancer with no prior treatment.
  5. Complete radiology or tumor assessment within 28 days prior to enrollment

    1. Breast MRI
    2. Unilateral Breast Ultrasound
    3. Distant metastatic work-up completed with PET/CT.
    4. If enlarged axillary lymph nodes are found during staging scans, FNA must be performed to determine whether the node is involved with cancer.
    5. If axillary lymph nodes are clinically negative during initial work-up, sentinel node biopsy will be performed prior to initiation of chemotherapy.
  6. ECOG Performance Status of 0 or 1
  7. Adequate organ and hematologic function as evidenced by the following laboratory studies within 4 weeks of study enrollment:

    1. Cardiac Ejection Fraction >/= lower limit of normal as determined by 2-D echo or MUGA scan according to institutional standards.
    2. Hematologic function, as follows: Absolute neutrophil count ≥ 1.5 x 109/L, Platelet count ≥ 100 x 109/L and ≤ 850 x 109/L, Hemoglobin ≥ 9 g/dL, PTT and INR < 1.5 x ULN.
    3. Renal function, as follows: Serum creatinine </= 1.4 mg/dL).
    4. Hepatic function, as follows:Aspartate aminotransferase (AST) ≤ 2.5 x ULN, Alanine aminotransferase (ALT) ≤ 2.5 x ULN , Total bilirubin ≤ 2 x ULN (except for patients with UGT1A1 promoter polymorphism, i.e. Gilbert syndrome, confirmed by genotyping or Invader UGT1A1 molecular assay prior to study enrollment. Patients enrolled with Gilbert syndrome must have total bilirubin < 3 ULN).
  8. Patient must be willing and able to undergo MRI as outlined in protocol.

Exclusion Criteria:

  1. Known hypersensitivity to doxorubicin, cyclophosphamide, paclitaxel, cremophor or medications containing cremophor(miconazole, docetaxel, sandimmune, nelfinavir mesylate, propofol, diazepam injection, vitamin K injection, ixabepilone, aci-jel) or carboplatin.
  2. Known HIV or active Hepatitis B or C infection.
  3. Prior treatment for the currently diagnosed breast cancer.
  4. Prior treatment with doxorubicin up to 400 mg/m2.
  5. Pre-existing Grade 3 or 4 sensory neuropathy.
  6. History of bleeding diathesis or extensive bleeding requiring blood transfusion within 14 days of enrollment.
  7. Major surgical procedure within 4 weeks (28 days) prior to enrollment (port placement is not considered a major surgical procedure).
  8. Clinically significant cardiac disease within 12 months of study enrollment, including myocardial infarction, unstable angina, congestive heart failure, or ongoing arrhythmias requiring medication or pacemaker.
  9. Non-healing wound, ulcer or fracture.
  10. Ongoing or active infection.
  11. Pregnant (i.e., positive beta-human chorionic gonadotropin test) or lactating
  12. Not willing to use a highly effective method of birth control (i.e. those which result in low failure rates, less than 1% per year), defined as intrauterine devices, barrier methods (condoms, contraceptive sponges, diaphragms, vaginal rings used with spermicidal jellies or creams), oral contraceptive pills, or sexual abstinence. Contraception must be used during the study.
  13. T0 tumors
  14. Active dental infection
  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: NCT01818063

Contacts
Contact: Tiffany Avery, MD, MPH 215-955-1661
Contact: Clinical Research Management Office 215-955-1661

Locations
United States, Maryland
Anne Arundel Medical Center Not yet recruiting
Annapolis, Maryland, United States, 21401
Contact: Lorraine Tafra, MD         
Principal Investigator: Lorraine Tafra, MD         
Walter Reed National Military Medical Center Not yet recruiting
Bethesda, Maryland, United States, 20889
Contact: Craig Shriber, MD         
Principal Investigator: Craig Shriber, MD         
United States, Pennsylvania
Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Tiffany Avery, MD, MPH    215-955-1661      
Contact: Clinical Research Management Office    215-955-1661      
Principal Investigator: Tiffany Avery, MD, MPH         
Sub-Investigator: Ronald Cantor, MD         
Sub-Investigator: Frederick Fellin, MD         
Sub-Investigator: Edith Mitchell, MD         
Sub-Investigator: Lewis Rose, MD         
Sub-Investigator: Michael Ramirez, MD         
Sub-Investigator: Allison Zibelli, MD         
Sub-Investigator: Andrew Chapman, DO         
Sub-Investigator: Avnish Bhatia, MD         
Sub-Investigator: Rebecca Jaslow, MD         
Sub-Investigator: Atrayee Basu Mallick, MD         
Sub-Investigator: Adam Berger, MD         
Sub-Investigator: Christina Brus, MD         
Sub-Investigator: Anne Rosenberg, MD         
Sub-Investigator: Juan Palazzo, MD         
Sub-Investigator: Massimo Cristofanilli, MD         
Sub-Investigator: Melissa Lazar, MD         
Sub-Investigator: Theodore Tsangaris, MD         
University of Pittsburgh Medical Center Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Shannon Pulhalla, MD         
Principal Investigator: Shannon Pulhalla, MD         
Sponsors and Collaborators
Thomas Jefferson University
Susan G. Komen Breast Cancer Foundation
Investigators
Principal Investigator: Tiffany Avery, MD, MPH Thomas Jefferson University
  More Information

Additional Information:
Publications:
NCCN. NCCN Clinical Practice Guidelines in Oncology, Version 2.2011. 2011.
O'Shaughnessy J, Schwartzberg S, Danso M, Rugo H, Miller K, Yardley D. A randomized phase III study of iniparib (BSI-201) in combination with gemcitabine/carboplatin (G/C) in metastatic triple-negative breast cancer (TNBC). J Clin Oncol 2011;29 (suppl; abstr 1007).

Responsible Party: Thomas Jefferson University
ClinicalTrials.gov Identifier: NCT01818063     History of Changes
Other Study ID Numbers: 12G.376, 2012-47
Study First Received: March 21, 2013
Last Updated: May 13, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Liposomal doxorubicin
Doxorubicin
Carboplatin
Paclitaxel
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on August 28, 2014