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A Dose Finding Phase 1 of Sarilumab Plus Capecitabine in HER2/Neu-Negative Metastatic Breast Cancer and a Single-arm, Historically-controlled Phase 2 Study of Sarilumab Plus Capecitabine in Stage I-III Triple Negative Breast Cancer With High-Risk Residual Disease (EMPOWER)

NCT04333706

Description:

This study will advance a novel and potent strategy to eliminate minimal residual disease (MRD) in triple negative breast cancer (TNBC) present even after multimodal treatment, thereby improving survival and increasing cure rate in this aggressive cancer. Patients with locally advanced TNBC are at high risk of developing lethal metastatic disease within 2 years of diagnosis, especially for those without a pathologic complete response (pCR) after neoadjuvant chemotherapy. The high risk occurs despite surgical excision of the primary tumor and axillary lymph nodes to eliminate residual disease.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase 1/2 Trial of Sarilumab Plus Capecitabine in Breast Cancer
  • Official Title: A Dose Finding Phase 1 of Sarilumab Plus Capecitabine in HER2/Neu-Negative Metastatic Breast Cancer and a Single-arm, Historically-controlled Phase 2 Study of Sarilumab Plus Capecitabine in Stage I-III Triple Negative Breast Cancer With High-Risk Residual Disease (EMPOWER)

Clinical Trial IDs

  • ORG STUDY ID: IRB20200115
  • NCT ID: NCT04333706

Conditions

  • Breast
  • Metastatic
  • Triple Negative
  • Cancer
  • Disseminated Tumor Cell

Interventions

DrugSynonymsArms
CapecitabineExperimental Phase 1: Cohort A

Purpose

This study will advance a novel and potent strategy to eliminate minimal residual disease (MRD) in triple negative breast cancer (TNBC) present even after multimodal treatment, thereby improving survival and increasing cure rate in this aggressive cancer. Patients with locally advanced TNBC are at high risk of developing lethal metastatic disease within 2 years of diagnosis, especially for those without a pathologic complete response (pCR) after neoadjuvant chemotherapy. The high risk occurs despite surgical excision of the primary tumor and axillary lymph nodes to eliminate residual disease.

Detailed Description

      The study will consist of two phases, I and II. Phase I will be made up of 2 patient cohorts,
      Cohorts A and B.

        -  Cohort A, will include Stage I to III TNBC patients with less than a complete pCR after
           neoadjuvant therapy who will be treated with capecitabine (1000mg/m2/BID; for 14 days
           every 21 days) as standard of care. This cohort will be used to determine baseline bone
           marrow disseminated tumor cells (BM DTC) response to capecitabine alone.

        -  Cohort B, will include patients with metastatic TNBC, HER2/neu-negative and hormone
           resistant breast cancer. A total of 4 doses of sarilumab will be given with the starting
           dose of 150 mg SQ at 3-weeks cycles given 3 days prior to each of the first 4 of 8
           cycles of capecitabine (1000 mg/m2/BID; for 14 days every 21 days). If dose escalation
           is possible, sarilumab will be administered every 3 weeks at 200 mg SQ for 4 doses.

      Phase II is a single arm study in Stage I to III TNBC with less than a complete pCR after
      neoadjuvant therapy evaluating the combination of sarilumab with capecitabine (1000mg/m2/BID;
      for 14 days every 21 days) as compared to historical control patients treated with
      capecitabine alone. There are 8 cycles of capecitabine. The first 4 cycles will be combined
      with sarilumab. The Phase II sarilumab dose will be determined by the Phase I best tolerated
      dose. In patients without bone marrow DTC clearance after 4 doses of sarilumab, 4 more doses
      of sarilumab will be given in combination with the last 4 cycles of capecitabine.
    

Trial Arms

NameTypeDescriptionInterventions
Experimental Phase 1: Cohort AExperimentalTo determine the status of Disseminated Tumor Cell (DTC) in bone marrow aspirate before and after adjuvant capecitabine only to establish the baseline response rate of bone marrow (BM) Disseminated Tumor Cell (DTC) to capecitabine alone.
  • Capecitabine
Experimental: Phase I: Cohort BExperimentalA dose finding study of sarilumab plus capecitabine in patients with metastatic TNBC and metastatic HER2/neu-negative and hormone resistant breast cancer.
    Phase 2 single arm studyExperimentalStudy of adjuvant sarilumab plus capecitabine in stage I to III TNBC with less than a pCR

      Eligibility Criteria

              Inclusion Criteria:
      
                -  A. Written informed consent obtained from the subject and the ability for the subject
                   to comply with all the study-related procedures.
      
                -  B. Both males and females ≥ eighteen years of age
      
                -  C. A clinical diagnosis of metastatic triple negative or hormone resistant,
                   Her2/neu-negative breast cancer that has been confirmed histologically at one point
                   during the course of the disease. TNBC is defined as ER/PR IHC positivity rate of <10%
                   and Her2Neu-negative (Phase I Cohort B only)
      
                -  D. A life expectancy of at least 6 months. (Phase I only)
      
                -  E. Any previous cytotoxic chemotherapy must have been a minimum of 3 weeks prior to
                   study drug administration. There is no limit on the number of prior therapies. For
                   ER/PR-positive tumors, endocrine therapy must have been included in at least one of
                   those prior regimens. Prior capecitabine is allowed only if not given in the treatment
                   regimen immediately prior to the enrollment in this study. (Phase I Cohort B only)
      
                -  F. A diagnosis of TNBC confirmed histologically and defined as ER/PR IHC positivity
                   rate of <10% and Her2/neu-negative. (Phase I Cohort A and Phase II only)
      
                -  G. A pathologic confirmation of stage I, or II, or III breast cancer with less than a
                   complete pCR, defined as the absence of residual invasive cancer in resected breast
                   specimen and sampled lymph nodes with residual noninvasive cancer or in situ disease
                   allowed. (Phase I Cohort A and Phase II only)
      
                -  H. Must not have received prior systemic treatment for breast cancer except for those
                   included in the neoadjuvant regimen and the neoadjuvant regimen must not have included
                   capecitabine nor sarilumab. (Phase I Cohort A and Phase II only)
      
                -  I. An ECOG Performance Status ≤2.
      
                -  J. Adequate organ function defined as:
      
                     1. Absolute neutrophil count (ANC) > 1500/mcl (use of G-CSF is allowed)
      
                     2. Platelets ≥ 100,000/mcl
      
                     3. Hemoglobin ≥ 9 (pRBC +/- ESA are allowed)
      
                     4. ALT ≤ 5 x ULN
      
                     5. AST ≤ 5 x ULN
      
                     6. Bilirubin ≤ 3 x ULN
      
                     7. GFR ≥ 30 ml/min
      
                -  K. Women of childbearing potential (WOCBP) must be using a highly effective method of
                   contraception to avoid pregnancy throughout the study and for at least 24 weeks after
                   the last dose of study drug to minimize the risk of pregnancy. Prior to study
                   enrollment, women of childbearing potential must be advised of the importance of
                   avoiding pregnancy during trial participation and the potential risk factors for an
                   unintentional pregnancy.
      
                -  L. Males with female partners of child-bearing potential must agree to use
                   physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy)
                   throughout the study and should avoid conceiving children for 24 weeks following the
                   last dose of study drug.
      
              Exclusion Criteria:
      
                -  A. Females or males of childbearing potential who are unwilling or unable to use an
                   acceptable method to avoid pregnancy for the entire study period and for at least 24
                   weeks after the last dose of study drug.
      
                -  B. Females who are pregnant or breastfeeding.
      
                -  C. History of any other disease, metabolic dysfunction, physical examination finding,
                   or clinical laboratory finding giving reasonable suspicion of a disease or condition
                   that contraindicates the use of protocol therapy or that might affect the
                   interpretation of the results of the study or that puts the subject at high risk for
                   treatment complications, in the opinion of the treating physician.
      
                -  D. Hepatitis B infection except for prior vaccination. (Phase I Cohort B and Phase II
                   only).
      
                -  E. Known history of tuberculosis injection. (Phase I Cohort B and Phase II only).
      
                -  F. A history of diverticulitis. (Phase I Cohort B and Phase II only).
      
                -  G. Use of live vaccines within 30 days prior to study treatment due to the risk of
                   infection. Examples of live vaccines include, but are not limited to, the following:
                   measles, mumps, rubella (MMR), varicella/zoster (chicken pox), yellow fever, rabies,
                   Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for
                   injection are generally killed virus vaccines and are allowed; however, intranasal
                   influenza vaccines (e.g. FluMist) are live attenuated vaccines and are not allowed.
                   (Phase I Cohort B and Phase II only)
      
                -  H. History of other malignancy that in the primary oncologist's estimation has at the
                   time of study participation a higher risk of recurrence or death than the
                   study-related cancer.
      
                -  I. Prisoners or subjects who are involuntarily incarcerated.
      
                -  J. Subjects who are compulsorily detained for treatment of either a psychiatric or
                   physical illness.
      
                -  K. Subjects demonstrating an inability to comply with the study and/or follow-up
                   procedures.
            
      Maximum Eligible Age:99 Years
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Phase I: Maximum Tolerated Dose (MTD)
      Time Frame:first treatment up to 9 weeks
      Safety Issue:
      Description:Establish MTD of sarilumab plus capecitabine in patients with metastatic TNBC and metastatic HER2/neu-negative and hormone resistant breast cancer

      Details

      Phase:Phase 1/Phase 2
      Primary Purpose:Interventional
      Overall Status:Not yet recruiting
      Lead Sponsor:University of Florida

      Last Updated

      April 1, 2020