Metastatic breast cancer with stable brain metastases MedDRA version: 19.0 Level: PT Classification code 10055113 Term: Breast cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 19.0 Level: PT Classification code 10006198 Term: Breast cancer recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: etirinotecan pegol drug product
Product Code: NKTR-102
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: etirinotecan pegol
CAS Number: 1193151-06-2
Current Spon
Sponsors
Nektar Therapeutics
Eligibility
Sex/Gender
All
Inclusion 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. - 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. For HER2-positive disease, a minimum of 2 cytotoxic chemotherapy regimens must have been administered for the indication of metastatic disease as well as at least 1 hormonal therapy. For HER2-positive disease, a minimum of 2 cytotoxic chemotherapy regimens must have been administered for the indication of metastatic disease as well as at least 1 HER2 targeted therapy (ado-trastuzumab emtansine is considered a cytotoxic chemotherapy regimen). - 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 - ECOG performance status of 0 or 1. - Adequate organ function obtained within 14 days prior to randomization and analyzed by the central laboratory as evidenced by: - Use highly effective methods of birth control throughout the duration of the study until 6 months following the last dose of study drug. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 280 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 70
Exclusion criteria
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. - Brain metastases amenable to local therapy but without completion of such therapy - 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. - Severe/uncontrolled illness within the previous 28 days 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 precludes informed consent or limit compliance.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare overall survival (OS) of patients who receive 145 mg/m2 NKTR-102 given once every 21 days (q21d) with OS of patients who receive Treatment of Physician’s Choice (TPC) selected from the following list of 7 single-agent intravenous (IV) therapies: eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel. TPC drugs will be administered per the standard of care.;Secondary Objective: • To compare the objective response rate (ORR) from NKTR-102 treatment with that of TPC • To compare progression-free survival (PFS) from NKTR-102 treatment with that of TPC • To compare the clinical benefit rate (CBR) from NKTR-102 treatment with that of TPC • To compare duration of response (DoR) from NKTR-102 treatment with that of TPC • To evaluate the safety profiles of NKTR-102 and TPC • To compare health-related quality of life from NKTR-102 treatment with that of TPC using the EORTC QLQ-C30 with the BN-20 questionnaire, the EQ-5D-5LTM questionnaire, and the Brief Fatigue Inventory (BFI) • To evaluate PK data (patients randomized to NKTR-102 only) • To correlate presence of reduced function UGT1A1 variants with NKTR-102 safety (patients randomized to NKTR-102 only) • To evaluate the pharmacoeconomic implications of NKTR-102 therapy using selected measures of health care utilization • To evaluate the magnitude of clinical benefit using ESMO-MCBS clinical benefit scale;Primary end point(s): Overall survival;Timepoint(s) of evaluation of this end point: Monitored throughout the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Progression-free survival (outside the CNS) Progression-free survival in brain metastases Objective response rate Clinical benefit rate Duration of response HRQoL Magnitude of Clinical Benefit;Timepoint(s) of evaluation of this end point: PFS outside the CNS, PFS in brain metastases, CBR and DoR - monitored throughout the study ORR - Screening, every 8 weeks through Week 24, then every 12 weeks thereafter HRQoL - Day 1 of each treatment Cycle prior to infusion and at End of Treatment visit | — |
Countries
Australia, Austria, Belgium, Canada, Czech Republic, France, Germany, Hungary, Ireland, Israel, Italy, Netherlands, New Zealand, Poland, Portugal, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Desk
Nektar Therapeutics Contact Center
Outcome results
None listed