A Study of Etirinotecan Pegol (NKTR-102) Versus Treatment of Physician's Choice (TPC) in Patients With Metastatic Breast Cancer Who Have Stable Brain Metastases and Have Been Previously Treated With an Anthracycline, a Taxane, and Capecitabine
Condition: Metastasis; Breast Cancer
MeSH terms: Breast Neoplasms; Neoplasm Metastasis; Brain Neoplasms
Intervention: NKTR-102; Eribulin; Ixabepilone; Vinorelbine; Gemcitabine; Paclitaxel; Docetaxel; Nab-paclitaxel
Intervention MeSH terms: Paclitaxel; Vinorelbine; Docetaxel; Albumin-Bound Paclitaxel; Gemcitabine; Etirinotecan pegol
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 178.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Breast Cancer Brain Metastases (BCBM); Carcinoma

Summary:

      This is an open-label, randomized, active comparator, multicenter, international Phase 3
      study of NKTR-102 versus TPC in patients with metastatic breast cancer who have stable brain
      metastases and have been previously treated with an anthracycline, a taxane, and capecitabine
      in either the adjuvant or metastatic setting (prior anthracycline may be omitted if medically
      appropriate or contraindicated for the patient).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Female or male, age ≥ 18 years.

          -  Histologically-confirmed carcinoma of the breast (either the primary or metastatic
             lesions) for whom single-agent cytotoxic chemotherapy is indicated. Patients may have
             either measurable or non-measurable disease according to RECIST version 1.1.

          -  Patients must have a history of brain metastases that are non-progressing.

          -  For triple-negative breast cancer, a minimum of 1 prior cytotoxic chemotherapy regimen
             must have been administered for the indication of metastatic disease.Depending on
             receptor status, 1 or 2 prior cytotoxic regimens are required prior to enrollment in
             this trial; hormonal and/or human epidermal growth factor receptor 2 (HER2) -targeted
             agents may be required.

          -  Have had prior therapy (administered in the neoadjuvant, adjuvant, and/or metastatic
             setting) with an anthracycline, a taxane, and capecitabine (prior anthracycline can be
             omitted if not medically appropriate or contraindicated for the patient).

          -  Last dose of anticancer therapy must have been administered within 6 months of the
             date of randomization into this study.

          -  All anticancer- and radiation therapy-related toxicities must be completely resolved
             or downgraded to Grade 1 or less (neuropathy may be Grade 2 or less).

          -  Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          -  Demonstrate adequate organ function obtained within 14 days prior to randomization and
             analyzed by the central laboratory.

          -  Women of childbearing potential (WCBP) must agree to use highly effective methods of
             birth control throughout the duration of the study until 6 months following the last
             dose of study drug.

          -  Males with female partners of child-bearing potential must agree to use a barrier
             contraception (e.g., condom with spermicidal foam/gel/film/cream/suppository)
             throughout the duration of the study until 6 months following the last dose of study
             drug; in addition to their female partner using either an intrauterine device or
             hormonal contraception and continuing until 6 months following the last dose of study
             drug. Male patients should not donate sperm until 6 months following the last dose of
             study drug.

        Exclusion Criteria:

          -  Last dose of anticancer therapy (including HER2-targeted therapy) within 14 days prior
             to randomization.

          -  High-dose chemotherapy followed by stem cell transplantation (autologous or
             allogeneic).

          -  Major surgery within 28 days prior to randomization.

          -  Concomitant use of any anticancer therapy or use of any investigational agent(s).

          -  Received prior treatment for cancer with a camptothecin-derived agent.

          -  Lesions on imaging, by cerebrospinal fluid or with neurological findings that are
             consistent with leptomeningeal disease or meningeal carcinomatosis.

          -  Chronic or acute GI disorders resulting in diarrhea of any severity grade.

          -  Patients who are pregnant or lactating, plan to get pregnant, or have a positive serum
             pregnancy test prior to randomization.

          -  Enzyme-inducing anti-epileptic drugs (EIAEDs) within 14 days of randomization.

          -  Hepatitis B or C, tuberculosis, or HIV.

          -  Cirrhosis.

          -  Prior malignancy (other than breast cancer) unless diagnosed and definitively treated
             more than 5 years prior to randomization.

          -  Daily use of oxygen supplementation.

          -  Significant known cardiovascular impairment.

          -  Prior treatment with NKTR-102.

          -  Psychiatric illness, social situation, or geographical situation that preclude
             informed consent or limit compliance.

          -  Known intolerance or hypersensitivity to any of the products used in this study or
             their excipients.

          -  For patients selecting vinorelbine or gemcitabine as the TPC agent, patients may not
             receive yellow fever vaccine in the 28 days prior to randomization.