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Platinum Based Chemotherapy or Capecitabine in Treating Patients With Residual Triple-Negative Basal-Like Breast Cancer Following Neoadjuvant Chemotherapy

This study is currently recruiting participants.
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Verified September 2016 by Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group )
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group )
ClinicalTrials.gov Identifier:
NCT02445391
First received: May 13, 2015
Last updated: September 29, 2016
Last verified: September 2016
May 13, 2015
September 29, 2016
April 2015
May 2019   (Final data collection date for primary outcome measure)
IDFS of patients with basal-like TNBC [ Time Frame: From randomization to the earliest of documented disease recurrence (local, regional and/or distant), invasive contralateral breast cancer, invasive any other second primary cancer, or death, assessed up to 86 months after study activation ]
The distributions of IDFS will be estimated using the Kaplan- Meier method. For the non-inferiority test, the primary analysis of IDFS comparisons will be performed using the repeated confidence interval (RCI) method with hazard ratio (HR) being estimated via stratified Cox proportional hazard model, stratifying on the randomization stratification factors. For the superiority tests of IDFS, the primary analysis will be performed using stratified log-rank tests, and stratified Cox proportional-hazard models will also be built to estimate the HRs for treatment effect for this efficacy endpoint a
IDFS of patients with basal-like TNBC [ Time Frame: From randomization to the earliest of documented disease recurrence (local, regional and/or distant), invasive contralateral breast cancer, invasive any other second primary cancer, or death, assessed up to 86 months after study activation ]
The distributions of IDFS will be estimated using the Kaplan- Meier method, with 95% confidence intervals (CI) calculated using Greenwood's formula. The primary analysis of IDFS comparisons between two treatment arms will be performed using stratified log-rank tests, stratifying on the randomization stratification factors. Stratified Cox proportional-hazard models will also be built to estimate the hazard ratios for treatment effect for IDFS as a supportive analysis.
Complete list of historical versions of study NCT02445391 on ClinicalTrials.gov Archive Site
  • Incidence of toxicity graded using the National Cancer Institute CTCAE v. 4.0 [ Time Frame: Up to 86 months after study activation ]
    All treatment-emergent and baseline adverse events and hematological/biochemical toxicities based on laboratory measurements will be summarized for patients on platinum agent. The incidence of deaths and treatment-emergent serious adverse events will be calculated along with exact 95% CI based on binomial distribution. Also, the incidence of adverse events leading to discontinuation of chemotherapy and/or withdrawal from the study will be summarized and listed as well.
  • OS of patients with basal-like TNBC with residual disease after neoadjuvant chemotherapy [ Time Frame: Time from randomization to death from any cause, assessed up to 116 months after study activation ]
    The distributions of OS will be estimated using the Kaplan- Meier method. For the superiority tests of OS, the primary analysis will be performed using stratified log-rank tests, and stratified Cox proportional-hazard models the will also be built to estimate the HRs for treatment effect for this efficacy endpoint as a supportive analysis
  • Rate of basal-like gene expression using PAM50 analysis by digital mRNA quantification [ Time Frame: Baseline ]
    The proportion of basal-like TNBC in all screened TNBC patients will be calculated with exact 95% CI based on binomial distribution.
  • RFS [ Time Frame: Up to 86 months after study activation ]
    The distributions of RFS will be estimated using the Kaplan- Meier method. For the superiority tests of RFS, the primary analysis will be performed using stratified log-rank tests, and stratified Cox proportional-hazard models the will also be built to estimate the HRs for treatment effect for this efficacy endpoint as a supportive analysis.
  • Incidence of toxicity graded using the National Cancer Institute CTCAE v. 4.0 [ Time Frame: Up to 86 months after study activation ]
    All treatment-emergent and baseline adverse events and hematological/biochemical toxicities based on laboratory measurements will be summarized for patients on platinum agent. The incidence of deaths and treatment-emergent serious adverse events will be calculated along with exact 95% CI based on binomial distribution. Also, the incidence of adverse events leading to discontinuation of chemotherapy and/or withdrawal from the study will be summarized and listed as well.
  • Overall survival (OS) of patients with basal-like TNBC with residual disease after neoadjuvant chemotherapy [ Time Frame: Time from randomization to death from any cause, assessed up to 116 months after study activation ]
    The distributions of OS will be estimated using the Kaplan- Meier method, with 95% CI calculated using Greenwood's formula. The primary analysis of OS comparisons between two treatment arms will be performed using stratified log-rank tests, stratifying on the randomization stratification factors.
  • Rate of basal-like gene expression using PAM50 analysis by digital mRNA quantification [ Time Frame: Baseline ]
    The proportion of basal-like TNBC in all screened TNBC patients will be calculated with exact 95% CI based on binomial distribution.
  • RFS [ Time Frame: Up to 86 months after study activation ]
    The distributions of RFS will be estimated using the Kaplan- Meier method, with 95% CI calculated using Greenwood's formula. The primary analysis of RFS comparisons between two treatment arms will be performed using stratified log-rank tests, stratifying on the randomization stratification factors.
Not Provided
Not Provided
 
Platinum Based Chemotherapy or Capecitabine in Treating Patients With Residual Triple-Negative Basal-Like Breast Cancer Following Neoadjuvant Chemotherapy
A Randomized Phase III Post-Operative Trial of Platinum Based Chemotherapy vs. Capecitabine in Patients With Residual Triple-Negative Basal-Like Breast Cancer Following Neoadjuvant Chemotherapy
This randomized phase III trial studies how well cisplatin or carboplatin (platinum based chemotherapy) works compared to capecitabine in treating patients with remaining (residual) basal-like triple-negative breast cancer following chemotherapy after surgery (neoadjuvant). Drugs used in chemotherapy, such as cisplatin, carboplatin and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether cisplatin or carboplatin is more effective than capecitabine in treating patients with residual triple negative basal-like breast cancer.

PRIMARY OBJECTIVES:

I. To compare the invasive disease-free survival (IDFS) in triple-negative breast cancer (TNBC) patients with residual basal-like disease after neoadjuvant chemotherapy who are randomized to post-preoperative platinum based chemotherapy with those who are randomized to capecitabine.

SECONDARY OBJECTIVES:

I. To evaluate overall survival (OS) and response-free survival (RFS) in the two arms in patients with TNBC with residual basal-like disease after neoadjuvant chemotherapy.

II. To characterize the side effects and tolerability of each platinum agent (cisplatin and carboplatin) as well as capecitabine in patients with TNBC with residual disease after neoadjuvant chemotherapy.

III. To identify the rate of basal-like gene expression using prediction analysis of microarray 50 (PAM50) analysis by digital messenger ribonucleic acid (mRNA) quantitation amongst drug-resistant residual TNBC after neoadjuvant chemotherapy.

IV. To compare the IDFS in TNBC patients with residual non-basal-like disease after neoadjuvant chemotherapy who are randomized to post-preoperative platinum based chemotherapy with those who are randomized to capecitabine (exploratory analysis).

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM A (closed to accrual 05/16/2016): Patients undergo observation.

ARM B: Patients receive cisplatin intravenously (IV) or carboplatin IV on day 1. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.

ARM C: Patients receive capecitabine orally (PO) twice daily (BID) on days 1-14. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for up to 10 years.

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Estrogen Receptor Negative
  • HER2/Neu Negative
  • Invasive Breast Carcinoma
  • Progesterone Receptor Negative
  • Stage IIA Breast Cancer
  • Stage IIB Breast Cancer
  • Stage IIIA Breast Cancer
  • Stage IIIB Breast Cancer
  • Stage IIIC Breast Cancer
  • Triple-Negative Breast Carcinoma
  • Drug: Capecitabine
    Given PO
    Other Names:
    • Ro 09-1978/000
    • Xeloda
  • Drug: Carboplatin
    Given IV
    Other Names:
    • Blastocarb
    • Carboplat
    • Carboplatin Hexal
    • Carboplatino
    • Carbosin
    • Carbosol
    • Carbotec
    • CBDCA
    • Displata
    • Ercar
    • JM-8
    • Nealorin
    • Novoplatinum
    • Paraplat
    • Paraplatin
    • Paraplatin AQ
    • Paraplatine
    • Platinwas
    • Ribocarbo
  • Drug: Cisplatin
    Given IV
    Other Names:
    • Abiplatin
    • Blastolem
    • Briplatin
    • CDDP
    • Cis-diammine-dichloroplatinum
    • Cis-diamminedichloridoplatinum
    • Cis-diamminedichloro Platinum (II)
    • Cis-diamminedichloroplatinum
    • Cis-dichloroammine Platinum (II)
    • Cis-platinous Diamine Dichloride
    • Cis-platinum
    • Cis-platinum II
    • Cis-platinum II Diamine Dichloride
    • Cismaplat
    • Cisplatina
    • Cisplatinum
    • Cisplatyl
    • Citoplatino
    • Citosin
    • Cysplatyna
    • DDP
    • Lederplatin
    • Metaplatin
    • Neoplatin
    • Peyrone's Chloride
    • Peyrone's Salt
    • Placis
    • Plastistil
    • Platamine
    • Platiblastin
    • Platiblastin-S
    • Platinex
    • Platinol
    • Platinol- AQ
    • Platinol-AQ
    • Platinol-AQ VHA Plus
    • Platinoxan
    • Platinum
    • Platinum Diamminodichloride
    • Platiran
    • Platistin
    • Platosin
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Active Comparator: Arm A (observation) (closed to accrual 05/16/2016)
    Patients undergo observation.
    Intervention: Other: Laboratory Biomarker Analysis
  • Experimental: Arm B (cisplatin or carboplatin)
    Patients receive cisplatin IV or carboplatin IV on day 1. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Carboplatin
    • Drug: Cisplatin
    • Other: Laboratory Biomarker Analysis
  • Experimental: Arm C (capecitabine)
    Patients receive capecitabine PO BID on days 1-14. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Capecitabine
    • Other: Laboratory Biomarker Analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
562
Not Provided
May 2019   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • ELIGIBILITY CRITERIA FOR SCREENING AND MOLECULAR PROFILING (STEP 0)
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 within 2 weeks prior to screening
  • Female and male patients must have histologically confirmed triple negative (estrogen receptor negative [ER-]/progesterone receptor negative [PR-]/human epidermal growth factor receptor-2 negative [HER2-]) invasive breast cancer, clinical stage II-III at diagnosis (American Joint Committee on Cancer [AJCC] 7th edition) based on initial evaluation by clinical examination and/or breast imaging

    • ER- and PR- should meet one of the following criteria:

      • =< 10% cells stain positive, with weak intensity score (Allred score =< 2)
      • =< 1% cells stain positive, with weak or intermediate intensity score (Allred score =< 2)
    • HER2 negative (not eligible for anti-HER2 therapy) will be defined as:

      • Immunohistochemistry (IHC) 0, 1+ without in situ hybridization (ISH) HER2/neu chromosome 17 ratio OR
      • IHC 2+ and ISH HER2/neu chromosome 17 ratio non-amplified with ratio less than 2.0 and if reported average HER2 copy number < 6 signals/cells OR
      • ISH HER2/neu chromosome 17 ratio non-amplified with ratio less than 2.0 and if reported average HER2 copy number < 6 signals/cells without IHC
      • NOTE: Patients that originally present with synchronous bilateral tumors are eligible provided both tumors are TNBC, and at least one of them fulfills the remainder eligibility criteria of the protocol
  • Patients must have completed neoadjuvant taxane +/- anthracycline; patients must NOT have received cisplatin or carboplatin or capecitabine as part of their neoadjuvant therapy regimen

    • NOTE: Patients who received preoperative therapy as part of a clinical trial may enroll
  • Must have completed definitive resection of primary tumor

    • Negative margins for both invasive and ductal carcinoma in situ (DCIS) are desirable, however patients with positive margins may enroll if the treatment team believes no further surgery is possible and patient has received radiotherapy; patients with margins positive for lobular carcinoma in situ (LCIS) are eligible
    • Either mastectomy or breast conserving surgery (including lumpectomy or partial mastectomy) is acceptable
    • Sentinel node biopsy post neoadjuvant chemotherapy (i.e. at the time of definitive surgery) is allowed; axillary dissection is encouraged in patients with lymph node involvement, but is not mandatory
  • Post neoadjuvant chemotherapy, patients must be found to have residual invasive cancer in the breast at the time of definitive surgery; residual cancer is defined as a contiguous focus of residual invasive cancer, in the breast, measuring >= 1 cm in diameter, and with more than minimal cellularity, as per local pathologist determination

    • NOTE: The presence of ductal carcinoma in situ (DCIS) without invasion does not qualify as residual invasive disease in the breast
  • Post-mastectomy radiotherapy is required for all patients with the following:

    • Primary tumor >= 5 cm (prior to neoadjuvant chemotherapy [clinically] or at the time of definitive surgery) or involvement of 4 or more lymph nodes at the time of definitive surgery
    • For patients with primary tumors < 5 cm or with < 4 involved lymph nodes prior to neoadjuvant chemotherapy and at the time of definitive surgery, provision of post-mastectomy radiotherapy is at the discretion of the treating physician

      • NOTE: Radiation of regional nodal basins is at the discretion of the treating radiation oncologist; patients enrolled in clinical trials addressing local therapy after neoadjuvant chemotherapy are allowed to enroll
  • Breast radiotherapy (whole breast or partial) is required for patients who underwent breast-conserving therapy, including lumpectomy or partial mastectomy
  • Laboratory values must be obtained within 8 weeks prior to screening for protocol therapy
  • Hemoglobin (Hgb) > 9.0 g/dL
  • Platelets > 100 mm^3
  • Absolute neutrophil count (ANC) > 1500 mm^3
  • Calculated creatinine clearance of > 50 mL/min using the Cockcroft-Gault formula
  • Bilirubin =< 1.5 x ULN upper limit of normal (except in patients with documented Gilbert's disease, who must have a total bilirubin =< 3.0 mg/dL)
  • Aspartate aminotransferase (AST, serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 x upper limit of normal (ULN)
  • Alanine aminotransferase (ALT, serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN
  • No stage IV (metastatic) disease, however no specific staging studies are required in the absence of symptoms or physical exam findings that would suggest distant disease
  • No clinically significant infections as judged by the treating investigator
  • Patients with active >= Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 4 grade 2 neuropathy are ineligible
  • Adjuvant chemotherapy after surgery other than that specified in this protocol is not allowed; luteinizing hormone-releasing hormone (LHRH) agonists and adjuvant bisphosphonate or denosumab use is allowed
  • Patients must have archived formalin-fixed paraffin-embedded (FFPE) tumor tissue specimen from the residual disease on the definitive surgical specimen available for PAM50 analysis for stratification

    • Tumor tissue specimen from the definitive surgery has been collected and is ready to ship to the ECOG-American College of Radiology Imaging Network (ACRIN) Central Biorepository and Pathology Facility (CBPF) within 12 weeks post-surgery
    • The Molecular Diagnostics Laboratory (MDL) at MD Anderson Cancer Center will perform the PAM50 analysis and notify the ECOG-American College of Radiology Imaging Network (ACRIN) operations office within three (3) weeks of receipt of the tumor tissue specimen via secure electronic messaging to the ECOG-ACRIN database

      • NOTE: Every effort should be made to submit the tumor tissue specimen to the ECOG-ACRIN CBPF immediately; tumor tissue cannot be accepted after 12 weeks (post surgery) in order to allow for PAM50 analysis
  • ELIGIBILITY CRITERIA FOR RANDOMIZATION (STEP 1): For patients randomized to the chemotherapy arms, cycle 1/day 1 (platinum based or capecitabine) must start within 1 week (5 working days) following randomization
  • ELIGIBILITY CRITERIA FOR RANDOMIZATION (STEP 1): Must have PAM50 analysis by digital mRNA quantitation on the formalin-fixed paraffin-embedded tumor tissue specimen (FFPE) of the residual disease in the breast or axilla resected at the time of definitive surgery completed
  • ELIGIBILITY CRITERIA FOR RANDOMIZATION (STEP 1): ECOG performance status 0 or 1 within 2 weeks prior to randomization
  • ELIGIBILITY CRITERIA FOR RANDOMIZATION (STEP 1): Patients must have completed adjuvant radiotherapy >= 2 weeks prior to randomization for protocol therapy, if applicable
  • ELIGIBILITY CRITERIA FOR RANDOMIZATION (STEP 1): Patients must have completed treatment with any investigational agent >= 30 days prior to randomization for protocol therapy, if applicable
  • ELIGIBILITY CRITERIA FOR RANDOMIZATION (STEP 1): Patients must be randomized within 24 weeks from surgery
  • ELIGIBILITY CRITERIA FOR RANDOMIZATION (STEP 1): Women must not be pregnant or breast-feeding; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to randomization to rule out pregnancy

    • A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months
  • ELIGIBILITY CRITERIA FOR RANDOMIZATION (STEP 1): Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse for the duration of their participation in the study
  • ELIGIBILITY CRITERIA FOR RANDOMIZATION (STEP 1): Hemoglobin (Hgb) > 9.0 g/dL
  • ELIGIBILITY CRITERIA FOR RANDOMIZATION (STEP 1): Platelets > 100 mm^3
  • ELIGIBILITY CRITERIA FOR RANDOMIZATION (STEP 1): Absolute neutrophil count (ANC) > 1500 mm^3
  • ELIGIBILITY CRITERIA FOR RANDOMIZATION (STEP 1): International normalized ratio (INR) =< 2 for subjects not on anticoagulants; INR =< 3 for subjects on warfarin
  • ELIGIBILITY CRITERIA FOR RANDOMIZATION (STEP 1): Calculated creatinine clearance of > 50 mL/min
  • ELIGIBILITY CRITERIA FOR RANDOMIZATION (STEP 1): Bilirubin =< 1.5 x ULN (except in patients with documented Gilbert's disease, who must have a total bilirubin =< 3.0 mg/dL)
  • ELIGIBILITY CRITERIA FOR RANDOMIZATION (STEP 1): Aspartate aminotransferase (AST, SGOT) =< 2.5 x ULN
  • ELIGIBILITY CRITERIA FOR RANDOMIZATION (STEP 1): Alanine aminotransferase (ALT, SGPT) =< 2.5 x ULN
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
South Africa,   United States
 
 
NCT02445391
EA1131
NCI-2014-01820 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
EA1131
EA1131 ( Other Identifier: ECOG-ACRIN Cancer Research Group )
EA1131 ( Other Identifier: CTEP )
U10CA180820 ( U.S. NIH Grant/Contract )
Yes
Not Provided
Not Provided
Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group )
ECOG-ACRIN Cancer Research Group
National Cancer Institute (NCI)
Principal Investigator: Ingrid Mayer ECOG-ACRIN Cancer Research Group
Eastern Cooperative Oncology Group
September 2016

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