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
概览
- 阶段
- 3 期
- 干预措施
- Carboplatin
- 疾病 / 适应症
- Estrogen Receptor Negative
- 发起方
- ECOG-ACRIN Cancer Research Group
- 入组人数
- 415
- 试验地点
- 1968
- 主要终点
- 3-year Invasive Disease-Free Survival (IDFS) Rate in Basal-Subtype Patients
- 状态
- 进行中（未招募）
- 最后更新
- 上个月
概览
简要总结
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.
详细描述
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.
研究者
入排标准
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Arm B (cisplatin or carboplatin)
Patients receive cisplatin IV or carboplatin IV on day 1. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Carboplatin
Arm B (cisplatin or carboplatin)
Patients receive cisplatin IV or carboplatin IV on day 1. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Cisplatin
Arm C (capecitabine)
Patients receive capecitabine PO BID on days 1-14. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Capecitabine
Arm A (observation) (closed to accrual 05/16/2016)
Patients undergo observation.
结局指标
主要结局
3-year Invasive Disease-Free Survival (IDFS) Rate in Basal-Subtype Patients
时间窗: 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.
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.
次要结局
- Proportion of Basal Subtype(Assessed at registration to step 0 (baseline))
- 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)
- Health-related Quality of Life (HRQL) at 6-month Assessment(Assessed at 6 months after randomization)
- 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.)
- Health-related Quality of Life (HRQL) at 15-month Assessment(Assessed at 15 months after randomization)