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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

NCT02915744

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).

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: 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
  • Official Title: A Phase 3 Open-Label, Randomized, Multicenter Study of 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

Clinical Trial IDs

  • ORG STUDY ID: 15-102-14
  • NCT ID: NCT02915744

Conditions

  • Metastasis
  • Breast Cancer

Interventions

DrugSynonymsArms
NKTR-102NKTR-102
EribulinTreatment of Physician's Choice (TPC)
IxabepiloneTreatment of Physician's Choice (TPC)
VinorelbineTreatment of Physician's Choice (TPC)
GemcitabineTreatment of Physician's Choice (TPC)
PaclitaxelTreatment of Physician's Choice (TPC)
DocetaxelTreatment of Physician's Choice (TPC)
Nab-paclitaxelTreatment of Physician's Choice (TPC)

Purpose

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).

Detailed 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).

      In Group A, NKTR-102 will be administered at a dose level of 145 mg/m2 on a q21d schedule as
      a 90-minute intravenous (IV) infusion on Day 1 of each treatment cycle. In Group B, TPC will
      be administered per standard of care. Patients randomized to TPC will receive single-agent
      IV chemotherapy, limited to choice of one of the following 7 agents: eribulin, ixabepilone,
      vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel.

      This study will randomize approximately 350 patients using a 1:1 randomization ratio and
      stratification based on geographic region, tumor receptor status, and Eastern Cooperative
      Oncology Group (ECOG) status. At Screening, the Investigator must determine which TPC will
      be offered to the patient.

      Data will be collected on subsequent anticancer therapies in both treatment groups from the
      time patients come off the study treatment until the time of primary data analysis for OS.

      An independent data monitoring committee (DMC) will assess interim safety and efficacy data.
    

Trial Arms

NameTypeDescriptionInterventions
NKTR-102ExperimentalIn Group A, NKTR-102 will be administered at a dose level of 145 mg/m2 on a q21d schedule as a 90-minute intravenous (IV) infusion on Day 1 of each treatment cycle.
  • NKTR-102
Treatment of Physician's Choice (TPC)Active ComparatorIn Group B, TPC will be administered per standard of care. Patients randomized to TPC will receive single-agent IV chemotherapy, limited to choice of one of the following 7 agents: eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel.
  • Eribulin
  • Ixabepilone
  • Vinorelbine
  • Gemcitabine
  • Paclitaxel
  • Docetaxel
  • Nab-paclitaxel

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.

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival (OS) of Patients
Time Frame:Within 3 years from study start
Safety Issue:
Description: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). Overall survival is defined as the time from the date of randomization to the date of death from any cause. Patients will be followed until their date of death or until final database closure. Patients who are lost-to-follow-up or are alive at the time of analysis will be censored at the time they were last known to be alive or at the date of event cut-off for OS analysis.

Secondary Outcome Measures

Measure:Progression-Free Survival (Outside the Central Nervous System)
Time Frame:Through study completion, an expected average of 1 year
Safety Issue:
Description:Progression-Free Survival (PFS) is defined as the time from the date of randomization to the earliest evidence of documented Progressive Disease (PD) or of death from any cause. The date of global deterioration or symptomatic deterioration will not be used as the date of PD.
Measure:Progression-Free Survival in Brain Metastasis (PFS-BM)
Time Frame:Through study completion, an expected average of 1 year
Safety Issue:
Description:Progression-Free Survival in Brain Metastasis (PFS-BM) is defined as the time from the date of randomization to the earliest evidence of documented Progressive Disease (PD) per Response Assessment in Neuro-Oncology—Brain Metastases (RANO-BM) in brain metastases or death from any cause. The PD will also be determined by the investigator's assessments.
Measure:Objective Response Rates (ORR) of the NKTR-102 Treatment and the Treatment of Physician's Choice (TPC)
Time Frame:Through study completion, an expected average of 1 year
Safety Issue:
Description:Objective Response Rate (ORR) will be defined as the proportion of patients with a confirmed Complete Response (CR) or Partial Response (PR) (RECIST for lesions outside the Central Nervous System (CNS); RANO-BM for CNS lesions) based upon the best response as assessed by the Investigator.
Measure:Clinical Benefit Rate (CBR)
Time Frame:For at least 4 months, with an expected average of 1 year
Safety Issue:
Description:Clinical Benefit Rate will be defined as the proportion of patients having a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) for at least 4 months (≥ 120 days). The SD duration of 4 months is selected to reflect the shorter life expectancy of study population.
Measure:Duration of Response (DoR)
Time Frame:Through study completion, an expected average of 1 year
Safety Issue:
Description:Duration of response (DoR) will be defined as the time from first documented CR or PR until the earliest evidence of disease progression or death from any cause.
Measure:Compare Health-Related Quality of Life (HRQoL) using the European Organisation for Treatment of Cancer (EORTC) Quality of Life Core 30 (QLQ-C30) module with the brain neoplasms 20-question (BN-20) subscale.
Time Frame:Through study completion, an expected average of 1 year
Safety Issue:
Description:
Measure:Compare Health-Related Quality of Life (HRQoL) using the the EuroQoL 5D (EQ-5D-5L™)
Time Frame:Through study completion, an expected average of 1 year
Safety Issue:
Description:
Measure:Compare Health-Related Quality of Life (HRQoL) using the Brief Fatigue Inventory (BFI)
Time Frame:Through study completion, an expected average of 1 year
Safety Issue:
Description:
Measure:Magnitude of Clinical Benefit
Time Frame:Through study completion, an expected average of 1 year
Safety Issue:
Description:The magnitude of clinical benefit of NKTR-102 will be assessed by the European Society for Medical Oncology magnitude of clinical benefit scale (ESMO-MCBS) (v1.0).
Measure:Maximum observed serum concentration (Cmax) of NKTR-102
Time Frame:Through study completion, an expected average of 1 year
Safety Issue:
Description:
Measure:Time of maximum observed serum concentration (Tmax) of NKTR-102
Time Frame:Through study completion, an expected average of 1 year
Safety Issue:
Description:
Measure:Area Under the serum Concentration time curve in the dosing interval (AUCtau) of NKTR-102
Time Frame:Through study completion, an expected average of 1 year
Safety Issue:
Description:
Measure:Half-life of (t1/2) of NKTR-102
Time Frame:Through study completion, an expected average of 1 year
Safety Issue:
Description:
Measure:Number of participants with adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.3
Time Frame:Through study completion, an expected average of 1 year
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Nektar Therapeutics

Trial Keywords

  • Breast Cancer Brain Metastases (BCBM)
  • Carcinoma

Last Updated

March 27, 2017