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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 (ATTAIN)

This study is currently recruiting participants.
Verified July 2017 by Nektar Therapeutics
Sponsor:
ClinicalTrials.gov Identifier:
NCT02915744
First Posted: September 27, 2016
Last Update Posted: July 28, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Nektar Therapeutics
  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).

Condition Intervention Phase
Metastasis Breast Cancer Drug: NKTR-102 Drug: Eribulin Drug: Ixabepilone Drug: Vinorelbine Drug: Gemcitabine Drug: Paclitaxel Drug: Docetaxel Drug: Nab-paclitaxel Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Nektar Therapeutics:

Primary Outcome Measures:
  • Overall Survival (OS) of Patients [ Time Frame: Within 3 years from study start ]
    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:
  • Progression-Free Survival (Outside the Central Nervous System) [ Time Frame: Through study completion, an expected average of 1 year ]
    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.

  • Progression-Free Survival in Brain Metastasis (PFS-BM) [ Time Frame: Through study completion, an expected average of 1 year ]
    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.

  • 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 ]
    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.

  • Clinical Benefit Rate (CBR) [ Time Frame: For at least 4 months, with an expected average of 1 year ]
    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.

  • Duration of Response (DoR) [ Time Frame: Through study completion, an expected average of 1 year ]
    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.

  • 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 ]
  • 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 ]
  • Compare Health-Related Quality of Life (HRQoL) using the Brief Fatigue Inventory (BFI) [ Time Frame: Through study completion, an expected average of 1 year ]
  • Magnitude of Clinical Benefit [ Time Frame: Through study completion, an expected average of 1 year ]
    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).

  • Maximum observed serum concentration (Cmax) of NKTR-102 [ Time Frame: Through study completion, an expected average of 1 year ]
  • Time of maximum observed serum concentration (Tmax) of NKTR-102 [ Time Frame: Through study completion, an expected average of 1 year ]
  • 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 ]
  • Half-life of (t1/2) of NKTR-102 [ Time Frame: Through study completion, an expected average of 1 year ]
  • 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 ]

Estimated Enrollment: 350
Study Start Date: November 2016
Estimated Study Completion Date: February 2020
Estimated Primary Completion Date: August 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NKTR-102
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.
Drug: NKTR-102
Active Comparator: Treatment of Physician's Choice (TPC)
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.
Drug: Eribulin Drug: Ixabepilone Drug: Vinorelbine Drug: Gemcitabine Drug: Paclitaxel Drug: Docetaxel Drug: Nab-paclitaxel

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02915744


Contacts
Contact: Nektar Recruitment 855-482-8676 StudyInquiry@nektar.com

  Show 41 Study Locations
Sponsors and Collaborators
Nektar Therapeutics
  More Information

Responsible Party: Nektar Therapeutics
ClinicalTrials.gov Identifier: NCT02915744     History of Changes
Other Study ID Numbers: 15-102-14
First Submitted: September 22, 2016
First Posted: September 27, 2016
Last Update Posted: July 28, 2017
Last Verified: July 2017

Keywords provided by Nektar Therapeutics:
Breast Cancer Brain Metastases (BCBM)
Carcinoma

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasm Metastasis
Neoplasms, Second Primary
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Paclitaxel
Vinorelbine
Docetaxel
Gemcitabine
Taxane
Albumin-Bound Paclitaxel
Capecitabine
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs


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