Clinical Trials /

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

NCT02445391

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Platinum</span> Based <span class="go-doc-concept go-doc-intervention">Chemotherapy</span> or Observation in Treating Patients With Residual Triple-Negative Basal-Like <span class="go-doc-concept go-doc-disease">Breast Cancer</span> Following <span class="go-doc-concept go-doc-intervention">Neoadjuvant Chemotherapy</span>

Title

  • Brief Title: Platinum Based Chemotherapy or Observation in Treating Patients With Residual Triple-Negative Basal-Like Breast Cancer Following Neoadjuvant Chemotherapy
  • Official Title: A Randomized Phase III Post-Operative Trial of Platinum Based Chemotherapy vs. Observation in Patients With Residual Triple-Negative Basal-Like Breast Cancer Following Neoadjuvant Chemotherapy
  • Clinical Trial IDs

    NCT ID: NCT02445391

    ORG ID: EA1131

    NCI ID: NCI-2014-01820

    Trial Conditions

    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

    Trial Interventions

    Drug Synonyms Arms
    Carboplatin Blastocarb, Carboplat, CARBOPLATIN, Carboplatin Hexal, Carboplatino, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplat, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo Arm B (cisplatin or carboplatin)
    Cisplatin 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, CISPLATIN, 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 Arm B (cisplatin or carboplatin)

    Trial Purpose

    This randomized phase III trial studies how well cisplatin or carboplatin (platinum based
    chemotherapy) works compared to observation in treating patients with remaining (residual)
    basal-like triple-negative breast cancer following chemotherapy after surgery (neoadjuvant).
    Drugs used in chemotherapy, such as cisplatin and carboplatin, 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 observation in treating patients with residual triple negative
    basal-like breast cancer.

    Detailed Description

    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
    observation.

    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) in patients with TNBC with residual basal-like 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.

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

    ARM A: 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.

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

    Trial Arms

    Name Type Description Interventions
    Arm A (observation) No Intervention Patients undergo observation.
    Arm B (cisplatin or carboplatin) Experimental 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. Carboplatin, Cisplatin

    Eligibility Criteria

    Inclusion Criteria:

    - 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 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

    - Whole breast radiotherapy 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 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 to determine patient eligibility

    - 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 forward results (eligible versus non-eligible)
    within three (3) weeks of receipt of the tumor tissue specimen to the ordering
    physician via FAX and to the ECOG-ACRIN Operations Office 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 arm, cycle 1/day 1 must start within 1 week (5 working days) following
    randomization

    - ELIGIBILITY CRITERIA FOR RANDOMIZATION (STEP 1): Must have basal-like gene expression
    on 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

    - 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
    15 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): 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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    IDFS of patients with basal-like TNBC

    Secondary Outcome Measures

    Incidence of toxicity graded using the National Cancer Institute CTCAE v. 4.0

    Overall survival (OS) of patients with basal-like TNBC with residual disease after neoadjuvant chemotherapy

    Rate of basal-like gene expression using PAM50 analysis by digital mRNA quantification

    RFS

    Trial Keywords