Trial of Sacituzumab Govitecan in Participants With Refractory/Relapsed Metastatic Triple-Negative Breast Cancer (TNBC)
Condition: Breast Cancer
MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms
Intervention: Sacituzumab govitecan; Eribulin; Capecitabine; Gemcitabine; Vinorelbine
Intervention description: 10 mg/kg administered as a slow intravenous (IV) infusion either by gravity or with an infusion pump. Infusion rate for the first 15 minutes will start with 50 mg/hour or less with a subsequent infusion of 100 to 200 mg/hour up to a maximum recommended rate (advanced every 15 to 30 minutes) of 500 mg/hour with a subsequent infusion of 1000 mg/hour.; Administered IV over 2 to 5 minutes at a dose 1.4 mg/m^2 at North American sites and 1.23 mg/m^2 at European sites on Days 1 and 8 of a 21-day cycle for up to 15.3 months. Lower doses will be administered on the same schedule to participants with moderate hepatic impairment (ie, Child-Pugh B; 0.7 mg/m^2 and 0.67 mg/m^2 for North American and European sites, respectively).; 1000 to 1250 mg/m^2 will be administered in a 21-day cycle, with capecitabine administered orally twice daily for 2 weeks followed by 1-week rest period for up to 10.6 months.; 800 to 1200 mg/m^2 will be administered IV over 30 minutes on Days 1, 8, and 15 of a 28-day cycle for up to 8.1 months.; 25 mg/m^2 will be administered as a weekly IV injection over 6-10 minutes for up to 11.5 months. Vinorelbine will not be allowed as TPC for any participant with Grade 2 neuropathy.
Intervention MeSH terms: Gemcitabine; Capecitabine; Vinorelbine; Sacituzumab govitecan
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 529.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objective of this study is to compare the efficacy of sacituzumab govitecan to
      the treatment of physician's choice (TPC) as measured by independently-reviewed Independent
      Review Committee (IRC) progression-free survival (PFS) in participants with locally advanced
      or metastatic triple-negative breast cancer (TNBC) previously treated with at least two
      systemic chemotherapy regimens for unresectable, locally advanced or metastatic disease, and
      without brain metastasis at baseline.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Histologically or cytologically confirmed TNBC based on the most recent analyzed
             biopsy or other pathology specimen. Triple negative is defined as <1% expression for
             estrogen receptor (ER) and progesterone receptor (PR) and negative for human epidermal
             growth factor receptor 2 (HER2) by in-situ hybridization.

          -  Refractory to or relapsed after at least two prior standard therapeutic regimens for
             advanced/metastatic TNBC.

          -  Prior exposure to a taxane in localized or advanced/metastatic setting.

          -  Eligible for one of the chemotherapy options listed as TPC (eribulin, capecitabine,
             gemcitabine, or vinorelbine) as per investigator assessment.

          -  Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1.

          -  Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) as
             per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Bone-only
             disease is not permitted.

          -  At least 2 weeks beyond prior anti-cancer treatment (chemotherapy, endocrine therapy,
             radiotherapy, and/or major surgery), and recovered from all acute toxicities to Grade
             1 or less (except alopecia and peripheral neuropathy).

          -  At least 2 weeks beyond high dose systemic corticosteroids (however, low dose
             corticosteroids < 20 mg prednisone or equivalent daily are permitted provided the dose
             is stable for 4 weeks).

          -  Adequate hematology without ongoing transfusional support (hemoglobin > 9 g/dL,
             absolute neutrophil count (ANC) > 1,500 per mm^3, platelets > 100,000 per mm^3).

          -  Adequate renal and hepatic function (creatinine clearance [CrCL] > 60 mL/min,
             bilirubin ≤ 1.5 institutional upper limit of normal [IULN], aspartate aminotransferase
             [AST] and alanine aminotransferase [ALT] ≤ 2.5 x IULN or ≤ 5 x IULN if known liver
             metastases and serum albumin ≥3 g/dL).

          -  Recovered from all toxicities to Grade 1 or less by National Cancer Institute common
             terminology criteria for adverse events (NCI CTCAE) v4.03 (except alopecia or
             peripheral neuropathy that may be Grade 2 or less) at the time of randomization.
             Participants with Grade 2 neuropathy are eligible but may not receive vinorelbine as
             TPC.

          -  Participants with treated, non-progressive brain metastases, off high-dose steroids
             (>20 mg prednisone or equivalent) for at least 4 weeks can be enrolled in the trial.

        Key Exclusion Criteria:

          -  Women who are pregnant or lactating.

          -  Women of childbearing potential or fertile men unwilling to use effective
             contraception during study and up to three months after treatment discontinuation in
             women of child-bearing potential and six months in males post last study drug.

          -  Participants with Gilbert's disease.

          -  Participants with non-melanoma skin cancer or carcinoma in situ of the cervix are
             eligible, while participants with other prior malignancies must have had at least a
             3-year disease-free interval.

          -  Participants known to be human immunodeficiency (HIV) positive, hepatitis B positive,
             or hepatitis C positive.

          -  Infection requiring antibiotic use within one week of randomization.

          -  Other concurrent medical or psychiatric conditions that, in the Investigator's
             opinion, may be likely to confound study interpretation or prevent completion of study
             procedures and follow-up examinations.

        Note: Other protocol defined Inclusion/Exclusion criteria may apply.