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

October 7, 2019 updated by: Sidney Kimmel Cancer Center at Thomas Jefferson University

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

1) To compare the pathologic complete response (path CR) in patients with stage IIB or stage III triple negative breast cancer treated with neoadjuvant paclitaxel and carboplatin to the path CR of patients treated with paclitaxel, carboplatin, and veliparib.

SECONDARY OBJECTIVES:

  1. Relapse free survival (follow-up period of 36 months).
  2. Overall clinical response to neoadjuvant therapy.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive paclitaxel intravenously (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.

ARM II: Patients receive veliparib orally (PO) twice daily (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.

After completion of study treatment, patients are followed up every 3 months for 36 months.

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20889
        • Walter Reed National Military Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University
      • Reading, Pennsylvania, United States, 19611
        • Reading Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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: Carboplatin
Given IV
Other Names:
  • Paraplatin
  • Paraplatin-AQ
  • cis-Diammine(1,1-cyclobutanedicarboxylato)platinum(II)
Drug: Paclitaxel
Given IV
Other Names:
  • Taxol
  • Abraxane
Drug: Cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • Endoxan
  • Neosar
  • Revimmune
  • Lyophilizedcytoxan
  • Procytox
  • cytophosphane
Drug: Doxorubicin
Given IV
Other Names:
  • Doxil
  • Adriamycin
  • Adriamycin PFS
  • Adriamycin RDF
  • hydroxydaunorubicin
  • Rubex
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: Carboplatin
Given IV
Other Names:
  • Paraplatin
  • Paraplatin-AQ
  • cis-Diammine(1,1-cyclobutanedicarboxylato)platinum(II)
Drug: Paclitaxel
Given IV
Other Names:
  • Taxol
  • Abraxane
Drug: Cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • Endoxan
  • Neosar
  • Revimmune
  • Lyophilizedcytoxan
  • Procytox
  • cytophosphane
Drug: Doxorubicin
Given IV
Other Names:
  • Doxil
  • Adriamycin
  • Adriamycin PFS
  • Adriamycin RDF
  • hydroxydaunorubicin
  • Rubex
Drug: Veliparib
Given PO
Other Names:
  • ABT-888

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Count of Participants That Achieve Pathologic Complete Response (PCR)
Time Frame: 36 months following surgery
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.
36 months following surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Clinical Response
Time Frame: Up to 3 years

The count and percentage 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]). Evaluated per Response Evaluation Criteria In Solid Tumors (RECIST v1.0) as assessed b MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Beta will be used as priors for combination regimens in calculating the posterior distribution of the pathologic complete response [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.
Up to 3 years
Relapse Free Survival
Time Frame: Up to 3 years
Analyzed using Kaplan-Meier methods, stratified by study group, and the log rank test will be completed.
Up to 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sidney Kimmel Cancer Center at Thomas Jefferson University

Collaborators

Susan G. Komen Breast Cancer Foundation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 25, 2013

Primary Completion (Actual)

March 1, 2015

Study Completion (Actual)

December 10, 2018

Study Registration Dates

First Submitted

March 21, 2013

First Submitted That Met QC Criteria

March 21, 2013

First Posted (Estimate)

March 26, 2013

Study Record Updates

Last Update Posted (Actual)

October 28, 2019

Last Update Submitted That Met QC Criteria

October 7, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 12G.376
  • 2012-47 (Other Identifier: CCRRC)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Stage II Breast Cancer

Clinical Trials on Carboplatin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in El Salvador

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe