Clinical Trial: NCT02445391 - My Cancer Genome

NCT02445391

Description:

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.

Related Conditions:

Invasive Breast Carcinoma

Recruiting Status:

Recruiting

Phase:

Phase 3

URL:

https://clinicaltrials.gov/show/NCT02445391

Trial Eligibility

Document

Title

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

Clinical Trial IDs

ORG STUDY ID: EA1131
SECONDARY ID: NCI-2014-01820
SECONDARY ID: EA1131
SECONDARY ID: EA1131
SECONDARY ID: EA1131
SECONDARY ID: U10CA180820
SECONDARY ID: U24CA196172
NCT ID: NCT02445391

Conditions

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

Interventions

Drug	Synonyms	Arms
Capecitabine	Ro 09-1978/000, Xeloda	Arm C (capecitabine)
Carboplatin	Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo	Arm B (cisplatin or carboplatin)
Cisplatin	Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin	Arm B (cisplatin or carboplatin)

Purpose

Detailed Description

      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.

Trial Arms

Name	Type	Description	Interventions
Arm A (observation) (closed to accrual 05/16/2016)	Active Comparator	Patients undergo observation.
Arm B (cisplatin or carboplatin)	Experimental	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.	Carboplatin Cisplatin
Arm C (capecitabine)	Experimental	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.	Capecitabine

Eligibility Criteria

        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

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Invasive disease-free survival (IDFS) of patients with basal-like triple-negative breast cancer (TNBC)
Time Frame:	From randomization to the earliest of documented disease recurrence (local, regional and/or distant), invasive contralateral breast cancer, invasive any other second primary cancer, or death, assessed up to 86 months after study activation
Safety Issue:
Description:	The distributions of IDFS will be estimated using the Kaplan- Meier method. For the non-inferiority test, the primary analysis of IDFS comparisons will be performed using the repeated confidence interval (RCI) method with hazard ratio (HR) being estimated via stratified Cox proportional hazard model, stratifying on the randomization stratification factors. For the superiority tests of IDFS, the primary analysis will be performed using stratified log-rank tests, and stratified Cox proportional-hazard models will also be built to estimate the HRs for treatment effect for this efficacy endpoint a

Secondary Outcome Measures

Measure:	Incidence of toxicity graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Time Frame:	Up to 86 months after study activation
Safety Issue:
Description:	All treatment-emergent and baseline adverse events and hematological/biochemical toxicities based on laboratory measurements will be summarized for patients on platinum agent. The incidence of deaths and treatment-emergent serious adverse events will be calculated along with exact 95% confidence interval (CI) based on binomial distribution. Also, the incidence of adverse events leading to discontinuation of chemotherapy and/or withdrawal from the study will be summarized and listed as well.

Measure:	Overall survival (OS) of patients with basal-like triple-negative breast cancer (TNBC) with residual disease after neoadjuvant chemotherapy
Time Frame:	Time from randomization to death from any cause, assessed up to 116 months after study activation
Safety Issue:
Description:	The distributions of OS will be estimated using the Kaplan- Meier method. For the superiority tests of OS, the primary analysis will be performed using stratified log-rank tests, and stratified Cox proportional-hazard models the will also be built to estimate the HRs for treatment effect for this efficacy endpoint as a supportive analysis

Measure:	Patient reported outcome (PRO)
Time Frame:	Up to 15 months
Safety Issue:
Description:	Standard descriptive and graphical analyses will be used initially to examine missing data patterns, and to understand the relationship between variables for health-related quality of life (HRQL) scores. The assessment scores for the HRQL will be compared between the two treatment arms at all time points, using two samples t test (or Wilcoxon rank sum test58 if the distribution of the score is not symmetric). Change in the HRQL scores between all other timepoints and the baseline visits will be compared between the two arms using two sample t tests. The mean score and proportion of moderate/se

Measure:	Rate of basal-like gene expression using PAM50 analysis by digital mRNA quantification
Time Frame:	Baseline
Safety Issue:
Description:	The proportion of basal-like TNBC in all screened TNBC patients will be calculated with exact 95% CI based on binomial distribution.

Measure:	Recurrence-free survival (RFS)
Time Frame:	Up to 86 months after study activation
Safety Issue:
Description:	The distributions of RFS will be estimated using the Kaplan- Meier method. For the superiority tests of RFS, the primary analysis will be performed using stratified log-rank tests, and stratified Cox proportional-hazard models the will also be built to estimate the HRs for treatment effect for this efficacy endpoint as a supportive analysis.

Details

Phase:	Phase 3
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	ECOG-ACRIN Cancer Research Group

Last Updated

May 21, 2020

Clinical Trials /

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