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

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).

V. To assess the difference in health-related quality of life (HRQL) between the platinum
based and capecitabine chemotherapy arms.

VI. To describe the rate of neurotoxicity over time in the platinum arm, the rate of
medication adherence in the capecitabine arm and the rates of amenorrhea in both arms
(exploratory).

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.

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 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

- No history of TNBC invasive breast cancer within 5 years of enrollment, no concurrent
malignancies of any sort

- 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 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

- 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

- 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): 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

- 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 > 100,000 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)
=< 3 (to be done/tested only for subjects on warfarin)

- ELIGIBILITY CRITERIA FOR RANDOMIZATION (STEP 1): Calculated creatinine clearance of >
50 mL/min using the Cockcroft-Gault formula

- 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