Platinum in Treating Patients With Residual Triple-Negative Breast Cancer Following Neoadjuvant Chemotherapy
Condition: 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
MeSH terms: Carcinoma; Breast Neoplasms
Intervention: Capecitabine; Carboplatin; Cisplatin
Intervention description: Given PO; Given IV; Given IV
Intervention MeSH terms: Cisplatin; Carboplatin; Capecitabine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 415.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Platinum; Capecitabine; Triple-negative breast cancer; Basal subtype; Neoadjuvant

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.
    

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 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