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

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ClinicalTrials.gov Identifier: NCT01818063
Recruitment Status : Completed
First Posted : March 26, 2013
Results First Posted : January 16, 2018
Last Update Posted : October 28, 2019
Sponsor:
Collaborator:
Susan G. Komen Breast Cancer Foundation
Information provided by (Responsible Party):
Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University )

Tracking Information
First Submitted Date  ICMJE March 21, 2013
First Posted Date  ICMJE March 26, 2013
Results First Submitted Date  ICMJE December 14, 2017
Results First Posted Date  ICMJE January 16, 2018
Last Update Posted Date October 28, 2019
Actual Study Start Date  ICMJE April 25, 2013
Actual Primary Completion Date March 1, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 16, 2018)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 21, 2013)
Pathologic complete response (PCR) [ Time Frame: At the time of 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. 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.
Change History Complete list of historical versions of study NCT01818063 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 7, 2019)
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 21, 2013)
  • Overall Clinical Response [ Time Frame: Up to 3 years ]
    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 ]
    Analyzed using Kaplan-Meier methods, stratified by study group, and the log rank test will be completed.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Carboplatin and Combination Chemotherapy With or Without Veliparib in Treating Patients With Stage IIB-IIIC Breast Cancer
Official Title  ICMJE 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
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Paclitaxel
    • Drug: Carboplatin
    • Drug: Doxorubicin
    • Drug: Cyclophosphamide
  • 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.
    Interventions:
    • Drug: Paclitaxel
    • Drug: Carboplatin
    • Drug: Doxorubicin
    • Drug: Cyclophosphamide
    • Drug: Veliparib
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 10, 2017)
9
Original Estimated Enrollment  ICMJE
 (submitted: March 21, 2013)
80
Actual Study Completion Date  ICMJE December 10, 2018
Actual Primary Completion Date March 1, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01818063
Other Study ID Numbers  ICMJE 12G.376
2012-47 ( Other Identifier: CCRRC )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University )
Study Sponsor  ICMJE Sidney Kimmel Cancer Center at Thomas Jefferson University
Collaborators  ICMJE Susan G. Komen Breast Cancer Foundation
Investigators  ICMJE
Principal Investigator: Edith Mitchell, MD Thomas Jefferson University
PRS Account Thomas Jefferson University
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP