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.
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 platinum agent 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 assess the difference in health-related quality of life (HRQL) between the platinum based and capecitabine chemotherapy arms. EXPLORATORY OBJECTIVES: I. 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. II. 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. III. To evaluate the association of genomic alterations identified via profiling of the surgical tumor specimen with RFS in patients with TNBC after neoadjuvant chemotherapy. IV. To explore whether any of the genomic alterations identified via profiling of the surgical tumor specimen can predict treatment benefit in patients with basal subtype TNBC. V. To determine the frequency of CTC positivity at baseline and after completion of study therapy in patients with TNBC with residual basal subtype disease after neoadjuvant chemotherapy. VI. To evaluate the associations between CTC levels at baseline, and after completion of chemotherapy, with RFS. VII. To evaluate the association between CTC change in status posttreatment (i.e. negative to negative, negative to positive, positive to negative, positive to positive) and RFS. VIII. To explore significance of CTC number/phenotype and ctDNA detected mutations (mutational burden, specific mutations) in predicting RFS. IX. 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 subtype disease after neoadjuvant chemotherapy. X. To evaluate the associations between plasma tumor cfDNA tumor specific mutations (baseline and after therapy) with RFS. XI. To explore optimal biomarker combination for RFS prediction. XII. 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). XIII. To determine the effects of tobacco on patient-reported physical symptoms and psychological symptoms. XIV. To examine quitting behaviors and behavioral counseling/support and cessation medication utilization. XV. 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 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
415
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
3-year Invasive Disease-Free Survival (IDFS) Rate in Basal-Subtype Patients
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.
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.
3-year Recurrence-Free Survival (RFS) Rate in Basal-Subtype Patients
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.
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.
3-year Overall Survival (OS) Rate in Basal-Subtype Patients
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.
Time frame: Assessed every 3 months within 2 years from randomization, every 6 months if 2-3 years
Proportion of Basal Subtype
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.
Time frame: Assessed at registration to step 0 (baseline)
Health-related Quality of Life (HRQL) at 6-month Assessment
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.
Time frame: Assessed at 6 months after randomization
Health-related Quality of Life (HRQL) at 15-month Assessment
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.
Time frame: Assessed at 15 months after randomization
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Alaska Oncology and Hematology LLC
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