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Platinum in Treating Patients With Residual Triple-Negative Breast Cancer Following Neoadjuvant Chemotherapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02445391
Recruitment Status : Active, not recruiting
First Posted : May 15, 2015
Results First Posted : October 5, 2022
Last Update Posted : December 9, 2022
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group )

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Estrogen Receptor Negative HER2/Neu Negative Invasive Breast Carcinoma Progesterone Receptor Negative Stage II Breast Cancer Stage IIA Breast Cancer Stage IIB Breast Cancer Stage III Breast Cancer Stage IIIA Breast Cancer Stage IIIB Breast Cancer Stage IIIC Breast Cancer Triple-Negative Breast Carcinoma Drug: Capecitabine Drug: Carboplatin Drug: Cisplatin Phase 3

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Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 415 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : April 29, 2015
Actual Primary Completion Date : April 7, 2021
Estimated Study Completion Date : March 29, 2031

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arms and Interventions
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Arm Intervention/treatment
No Intervention: Arm A (observation) (closed to accrual 05/16/2016)
Patients undergo observation.
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.
 Drug: Carboplatin
Given IV
Other Names:
  • Paraplatin
  • Carboplatin Novaplus

Drug: Cisplatin
Given IV
Other Names:
  • Platinol-AQ
  • Platinol
Active Comparator: 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.
 Drug: Capecitabine
Given PO
Other Name: Xeloda


Outcome Measures
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Primary Outcome Measures :
  1. 3-year Invasive Disease-Free Survival (IDFS) Rate in Basal-Subtype Patients [ Time Frame: No mandatory timeline, assessed at any time as a standard of care procedure or at the investigator's discretion; data reported every 3 months within 2 years from randomization, every 6 months if 2-3 years. ]
    IDFS was defined to be time from randomization to the earliest of documented disease recurrence (local, regional and/or distant), invasive contralateral breast cancer, invasive any other second cancer, or death. Cases with incomplete follow up or without adequate disease evaluations were censored at the date last documented to be free of IDFS events. 3-year IDFS rate was estimated using Kaplan-Meier method.


Secondary Outcome Measures :
  1. 3-year Recurrence-Free Survival (RFS) Rate in Basal-Subtype Patients [ Time Frame: No mandatory timeline, assessed at any time as a standard of care procedure or at the investigator's discretion; data reported every 3 months within 2 years from randomization, every 6 months if 2-3 years. ]
    RFS was defined as time from randomization to local/regional recurrence, distant recurrence or death, whichever occurred first. Cases with incomplete follow up or without adequate disease evaluations were censored at the date last documented to be free of RFS events. 3-year RFS rate was estimated using Kaplan-Meier method.

  2. 3-year Overall Survival (OS) Rate in Basal-Subtype Patients [ Time Frame: Assessed every 3 months within 2 years from randomization, every 6 months if 2-3 years ]
    OS was defined as time from randomization to death from any cause. Patient alive were censored at date of known alive. The 3-year OS rate was estimated using Kaplan-Meier method.

  3. Proportion of Basal Subtype [ Time Frame: Assessed at registration to step 0 (baseline) ]
    Proportion of basal subtype was calculated as number of patients who had basal subtype disease divided by all triple-negative breast cancers who were randomized to arms B and C after 6/22/2016 and had intrinsic subtype results.

  4. Health-related Quality of Life (HRQL) at 6-month Assessment [ Time Frame: Assessed at 6 months after randomization ]
    HRQL was measured by the Functional Assessment of Cancer Therapy Breast Symptom Index (FBSI) Treatment Side Effects (TSE) subscale score, an aggregate score of 4 items (GP2, GP5, N6 and B5) from the FBSI-16 scale. The FBSI TSE subscale score was calculated based on the scoring manual, score ranges from 0 to 16, higher scores indicate better quality of life.

  5. Health-related Quality of Life (HRQL) at 15-month Assessment [ Time Frame: Assessed at 15 months after randomization ]
    HRQL was measured by the Functional Assessment of Cancer Therapy Breast Symptom Index (FBSI) Treatment Side Effects (TSE) subscale score, an aggregate score of 4 items (GP2, GP5, N6 and B5) from the FBSI-16 scale. The FBSI TSE subscale score was calculated based on the scoring manual, score ranges from 0 to 16, higher scores indicate better quality of life.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

ELIGIBILITY CRITERIA FOR SCREENING AND MOLECULAR PROFILING (STEP 0)

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 invasive breast cancer that meets the following criteria:

    • Clinical stage II-III (American Joint Committee on Cancer [AJCC] 7th edition) at diagnosis, based on initial evaluation by clinical examination and/or breast imaging; no metastatic disease allowed

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

      • =< 10% cells stain positive, with weak intensity score (equivalent to Allred score =< 3)
      • =< 1% cells stain positive, with weak or intermediate intensity score (equivalent to Allred score =< 3)

    • 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; multifocal or multicentric breast cancers are eligible as long as all tumors fulfill eligibility criteria
      • NOTE: Patients that have a discrepancy in ER/PR/HER2 status between original diagnosis and surgical specimen (if ER/PR/HER2 status were repeated) are not eligible for study participation (i.e. ER/PR/HER2 has to fulfill above criteria in both scenarios)

  • 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
    • NOTE: Patients that were not able to complete their planned neoadjuvant chemotherapy for any reason (i.e. toxicities, etc.) are eligible to participate as long as no further systemic standard of care therapy is planned by the treating physician

  • 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 either pre or post neoadjuvant chemotherapy (i.e. at the time of definitive surgery) are 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; this is required due to constraints in deoxyribonucleic acid (DNA) extraction for PAM50 analysis

    • NOTE: The presence of ductal carcinoma in situ (DCIS) without invasion does not qualify as residual invasive disease in the breast
    • NOTE: Despite lymph node involvement if residual invasive cancer in the breast is < 1 cm in diameter patients are not eligible for participation

  • Radiotherapy may be given before or after protocol treatment per standard of care guidelines; when radiotherapy is planned prior to protocol treatment administration, patients may be registered and screened while receiving radiation

    • 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
      • Radiation of regional nodal basins is at the discretion of the treating radiation oncologist
    • NOTE: Breast radiotherapy (whole breast or partial) is required for patients who underwent breast-conserving therapy, including lumpectomy or partial mastectomy
  • Hemoglobin (Hgb) > 9.0 g/dL
  • Platelets > 100,000 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
  • 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 21 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; results will not be reported to the submitting institution
    • NOTE: Tissue must be submitted any time during screening period, even if patient is getting radiation
    • NOTE: Every effort should be made to submit the tumor tissue specimen to the ECOG-ACRIN CBPF immediately

Exclusion Criteria:

  • History of TNBC invasive breast cancer within 5 years of enrollment, no concurrent malignancies of any sort
  • Clinically significant infections as judged by the treating investigator

ELIGIBILITY CRITERIA FOR RANDOMIZATION (STEP 1):

  • No specific timeframe between registration and randomization needs to be observed, as long as:

    • Patients randomized to the chemotherapy arms have their cycle 1/ day 1 (platinum based or capecitabine) start within 3 weeks (15 working days) following randomization date
    • Randomization occurs no more than 24 weeks from surgery date
  • 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
  • ECOG performance status 0 or 1 within 2 weeks prior to randomization
  • Radiotherapy may be given before or after protocol treatment. when radiotherapy is planned prior to protocol treatment administration, patients must have completed adjuvant radiotherapy >= 2 weeks prior to randomization for protocol therapy, if applicable
  • Patients must have completed treatment with any investigational agent >= 30 days prior to randomization for protocol therapy, if applicable
  • Patients must be randomized within 24 weeks from surgery

  • 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
  • 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
  • Hemoglobin (Hgb) > 9.0 g/dL
  • Platelets > 100,000 mm^3
  • Absolute neutrophil count (ANC) > 1500 mm^3
  • International normalized ratio (INR) =< 3 (to be done/tested only for subjects on warfarin)
  • Calculated creatinine clearance of > 50 mL/min using the Cockcroft-Gault formula
  • Bilirubin =< 1.5 x ULN (except in patients with documented Gilbert?s disease, who must have a total bilirubin =< 3.0 mg/dL)
  • Aspartate aminotransferase (AST, SGOT) =< 2.5 x ULN
  • Alanine aminotransferase (ALT, SGPT) =< 2.5 x ULN
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02445391


Locations
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Sponsors and Collaborators
ECOG-ACRIN Cancer Research Group
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Ingrid Mayer ECOG-ACRIN Cancer Research Group
  Study Documents (Full-Text)

Documents provided by Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group ):
Study Protocol and Statistical Analysis Plan  [PDF] March 1, 2021

More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: ECOG-ACRIN Cancer Research Group
ClinicalTrials.gov Identifier: NCT02445391    
Other Study ID Numbers: EA1131
NCI-2014-01820 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
EA1131 ( Other Identifier: ECOG-ACRIN Cancer Research Group )
EA1131 ( Other Identifier: CTEP )
U10CA180820 ( U.S. NIH Grant/Contract )
U24CA196172 ( U.S. NIH Grant/Contract )
First Posted: May 15, 2015    Key Record Dates
Results First Posted: October 5, 2022
Last Update Posted: December 9, 2022
Last Verified: December 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy
Keywords provided by Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group ):
Platinum
Capecitabine
Triple-negative breast cancer
Basal subtype
Neoadjuvant
Additional relevant MeSH terms:
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Carcinoma
Breast Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
 Cisplatin
Carboplatin
Capecitabine
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action