Testing Platinum-based Chemotherapy after Surgery in Triple-Negative Breast Cancers

Summary

Objectives

PRIMARY OBJECTIVE:
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 CLINICAL 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).

SECONDARY CORRELATIVE BIOMARKER OBJECTIVES:
I. To evaluate the association of genomic alterations identified via profiling of the surgical tumor specimen with RFS in patients with TNBC after neoadjuvant chemotherapy.
II. To explore whether any of the genomic alterations identified via profiling of the surgical tumor specimen can predict treatment benefit in patients with basal-like TNBC.
III. To determine the frequency of CTC positivity at baseline and after completion of study therapy in patients with TNBC with residual basal-like disease after neoadjuvant chemotherapy.
IV. To evaluate the associations between CTC levels at baseline, and after completion of chemotherapy, with RFS.
V. To evaluate the association between CTC change in status post-treatment (i.e. negative to negative, negative to positive, positive to negative, positive to positive) and RFS.
VI. To explore significance of CTC number/phenotype and ctDNA-detected mutations (mutational burden, specific mutations) in predicting RFS.

EXPLORATORY CORRELATIVE BIOMARKER OBJECTIVES:
I. To determine the frequency of plasma tumor cell-free DNA (cfDNA) positivity at baseline and after completion of study therapy in patients with TNBC with residual basal-like disease after neoadjuvant chemotherapy.
II. To evaluate the associations between plasma tumor cfDNA tumor-specific mutations (baseline and after therapy) with RFS.
III. To explore optimal biomarker combination for RFS prediction.

EXPLORATORY TOBACCO USE OBJECTIVES:
I. To determine the effects of tobacco, operationalized as combustible tobacco (1a), other forms of tobacco (1b), and environmental tobacco exposure (ETS) (1c) on provider-reported cancer-treatment toxicity (adverse events [both clinical and hematologic] and dose modifications).
II. To determine the effects of tobacco on patient-reported physical symptoms and psychological symptoms.
III. To examine quitting behaviors and behavioral counseling/support and cessation medication utilization.
IV. To explore the effect of tobacco use and exposure on treatment duration, relative dose intensity, and therapeutic benefit.

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 cycles 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 cycles in the absence of disease progression or unacceptable toxicity.

Patients undergo blood sample collection while on study and during follow up.