A PHASE 3 OPEN-LABEL, RANDOMIZED, MULTICENTER STUDY OF NKTR-102 VERSUS TREATMENT OF PHYSICIANS 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
Trial Description
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 Requirements
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.