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

Official 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.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 415 participants

Interventions

• DRUG: Capecitabine — Given PO
• DRUG: Carboplatin — Given IV
• DRUG: Cisplatin — Given IV

Primary Outcomes

• 3-year Invasive Disease-Free Survival (IDFS) Rate in Basal-Subtype Patients (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.)

Secondary Outcomes

• 3-year Recurrence-Free Survival (RFS) Rate in Basal-Subtype Patients (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.)
• 3-year Overall Survival (OS) Rate in Basal-Subtype Patients (Assessed every 3 months within 2 years from randomization, every 6 months if 2-3 years)
• Proportion of Basal Subtype (Assessed at registration to step 0 (baseline))
• Health-related Quality of Life (HRQL) at 6-month Assessment (Assessed at 6 months after randomization)
• Health-related Quality of Life (HRQL) at 15-month Assessment (Assessed at 15 months after randomization)

Eligibility 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 Co

Trial Locations

• Mobile Infirmary Medical Center, Mobile, Alabama, United States
• University of South Alabama Mitchell Cancer Institute, Mobile, Alabama, United States
• Anchorage Associates in Radiation Medicine, Anchorage, Alaska, United States
• Anchorage Radiation Therapy Center, Anchorage, Alaska, United States
• Alaska Breast Care and Surgery LLC, Anchorage, Alaska, United States
• Alaska Oncology and Hematology LLC, Anchorage, Alaska, United States
• Alaska Regional Hospital, Anchorage, Alaska, United States
• Alaska Women's Cancer Care, Anchorage, Alaska, United States
• Anchorage Oncology Centre, Anchorage, Alaska, United States
• Katmai Oncology Group, Anchorage, Alaska, United States
• ...and 10 more locations

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