Trial record 1 of 1 for:    NCT01818063
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Carboplatin and Combination Chemotherapy With or Without Veliparib in Treating Patients With Stage IIB-IIIC Breast Cancer

This study is currently recruiting participants.
Verified January 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: January 7, 2014
Last verified: January 2014

March 21, 2013
January 7, 2014
April 2013
April 2018   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01818063 on ClinicalTrials.gov Archive Site
  • 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.
Same as current
Not Provided
Not Provided
 
Carboplatin and Combination Chemotherapy With or Without Veliparib in Treating Patients With Stage IIB-IIIC Breast Cancer
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.

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.
  3. To determine whether expression of 5 biomarkers (cytokeratin [CK]5, endothelial growth factor receptor [EGFR], excision repair cross complementing 1 [ERCC1], Ki67, poly[adenosine diphosphate (ADP)-ribosyl]transferase [Parp1]) correlate with a higher pCR in response to a particular treatment combination. 4) To determine whether tumors with biomarker signatures that are most like breast cancer (BRCA)-mutated tumors (high expression of CK5 and high expression of EGFR), will correlate with a higher likelihood of pCR with treatment with a PARP inhibitor in combination with chemotherapy.

5) To determine whether tumors with high expression of the markers ERCC1, Ki67, and Parp1 will correlate with a higher rate of pCR with platinum agents in combination with paclitaxel or a PARP inhibitor.

6) To correlate response of tumor on imaging (magnetic resonance imaging [MRI], ultrasound [US], and positron emission tomography [PET]/computed tomography [CT]) with path CR.

7) To correlate levels of circulating tumor cells (CTCs) with pathologic CR.

TERTIARY OBJECTIVES:

  1. To evaluate additional exploratory biomarkers based on evidence of possible prognostic or predictive value: BRCA1/BRCA2 complete mutational and rearrangement test. CK14, CK17, cyclin B1, cluster of differentiation (CD)44, CD24, cyclin D1, vimentin, thymidine phosphorylase, inhibitor of differentiation (ID)4, p53, p63, p73, differentiated embryo-chondrocyte expressed gene (Dec)1, phospho-HistoneH3, thymidylate synthase, p16, gammaH2AX, geminin, RAD51.
  2. To determine which arms are best tolerated by patients with co-morbid conditions, such as hypertension and diabetes.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
    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
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
80
Not Provided
April 2018   (final data collection date for primary outcome measure)

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 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. Bilateral Mammogram
    4. Distant metastatic work-up completed with PET/CT.
    5. If enlarged axillary lymph nodes are found during staging scans, FNA must be performed to determine whether the node is involved with cancer.
    6. 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.
  9. Tumor clip placement.

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. History of prior cancer. History of basal cell or squamous cell skin cancer is permitted.
  14. Inflammatory Breast Cancer
  15. T0 tumors
  16. Active dental infection
Female
18 Years and older
No
Contact: Tiffany Avery, MD, MPH 215-955-1661
Contact: Clinical Research Management Office 215-955-1661
United States
 
NCT01818063
12G.376, 2012-47
Yes
Thomas Jefferson University
Thomas Jefferson University
Susan G. Komen Breast Cancer Foundation
Principal Investigator: Tiffany Avery, MD, MPH Thomas Jefferson University
Thomas Jefferson University
January 2014

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