Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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)

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.
ClinicalTrials.gov Identifier: NCT02915744
Recruitment Status : Recruiting
First Posted : September 27, 2016
Last Update Posted : March 6, 2019
Sponsor:
Information provided by (Responsible Party):
Nektar Therapeutics

Brief 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).

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

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 220 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 and determine final number of death events needed to provide 80% conditional power based on the zone adaptive design.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 220 participants
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
Study Start Date : November 2016
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : March 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
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



Primary Outcome Measures :
  1. 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 :
  1. 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.

  2. 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.

  3. Progression-Free Survival (Overall) [ Time Frame: Through study completion, an expected average of 1 year ]
    Progression-free survival (CNS and peripheral) is defined as the time from the date of randomization to the earliest evidence of documented PD in either the CNS or peripheral (using RANO-BM) or death from any cause. The PD will be determined by both the investigator's and the central imaging facility assessments. The same statistical methods that were used for PFS and PFS-BM will be used for PFS (Overall).

  4. 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 central imaging facility. As a secondary analysis, ORR will be calculated based on the Investigator assessment of response.

  5. 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. CBR will be calculated based on both the central imaging facility assessment of response, progression and stability of disease, as well as the investigator's assessment of these parameters.

  6. Duration of Response (DoR) [ Time Frame: Through study completion, an expected average of 1 year ]
    Duration of response (DoR) outside the CNS will be defined as the time from first documented CR or PR until the earliest evidence of disease progression per RECIST v1.1 or death from any cause. DoR will be calculated based on the central imaging facility assessment of response and progression as well as the investigator's assessment of response and progression.

  7. WBRT [ Time Frame: Through study completion, an expected average of 1 year ]
    To compare the incidence and cumulative frequency of WBRT after date of randomization by treatment group. The protocol will also compare time-to-WBRT (defined as the date of first whole-brain radiation fraction) in those patients who received WBRT after the date of randomization by treatment group.

  8. 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 ]
  9. 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 ]
  10. Compare Health-Related Quality of Life (HRQoL) using the Brief Fatigue Inventory (BFI) [ Time Frame: Through study completion, an expected average of 1 year ]
  11. 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).

  12. Maximum observed serum concentration (Cmax) of NKTR-102 [ Time Frame: Through study completion, an expected average of 1 year ]
  13. Time of maximum observed serum concentration (Tmax) of NKTR-102 [ Time Frame: Through study completion, an expected average of 1 year ]
  14. 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 ]
  15. Half-life of (t1/2) of NKTR-102 [ Time Frame: Through study completion, an expected average of 1 year ]
  16. 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 ]


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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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.
  • 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.

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
Layout table for location contacts
Contact: Nektar Recruitment 855-482-8676 StudyInquiry@nektar.com

  Hide Study Locations
Locations
Layout table for location information
United States, Arizona
Investigator Site - Tucson Recruiting
Tucson, Arizona, United States, 85724
United States, California
Investigator Site - Orange Recruiting
Orange, California, United States, 92868
Investigator Site - San Francisco Recruiting
San Francisco, California, United States, 94115
United States, Florida
Investigator Site - Miami Recruiting
Miami, Florida, United States, 33136
Investigator Site - Plantation Terminated
Plantation, Florida, United States, 33324
Investigator Site - West Palm Beach Recruiting
West Palm Beach, Florida, United States, 33401
United States, Georgia
Investigator Site - Athens Recruiting
Athens, Georgia, United States, 30607
United States, Maryland
Investigator Site - Baltimore Recruiting
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Investigator Site - Boston Recruiting
Boston, Massachusetts, United States, 02115
United States, Minnesota
Investigator Site - Minneapolis Recruiting
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Investigator Site - Saint Louis Recruiting
Saint Louis, Missouri, United States, 63110
United States, New York
Investigator Site - New York Recruiting
New York, New York, United States, 10065
United States, North Carolina
Investigator Site - Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Investigator Site - Columbus Recruiting
Columbus, Ohio, United States, 43210
United States, Tennessee
Investigator Site - Germantown Recruiting
Germantown, Tennessee, United States, 38138
Investigator Site - Nashville Withdrawn
Nashville, Tennessee, United States, 37203
United States, Texas
Investigator Site - Fort Worth Recruiting
Fort Worth, Texas, United States, 76104
Investigator Site - Houston Recruiting
Houston, Texas, United States, 77030
United States, Utah
Investigator Site - Salt Lake City Recruiting
Salt Lake City, Utah, United States, 84106
United States, Washington
Investigator Site - Seattle Recruiting
Seattle, Washington, United States, 98109
Australia, New South Wales
Investigatory Site - Albury Recruiting
Albury, New South Wales, Australia, 2640
Investigator Site - Darlinghurst Recruiting
Darlinghurst, New South Wales, Australia, 2010
Investigator Site - Wollongong Recruiting
Wollongong, New South Wales, Australia, 2500
Australia, Queensland
Investigator Site - Brisbane Recruiting
Brisbane, Queensland, Australia, 4101
Australia, Western Australia
Investigator Site - Subiaco Recruiting
Subiaco, Western Australia, Australia, 6008
Australia
Investigator Site - Box Hill Recruiting
Box Hill, Australia, 3128
Investigator Site - Nedlands Recruiting
Nedlands, Australia, 6009
Belgium
Investigator Site - Brussels Recruiting
Brussels, Belgium, 1000
Investigator Site - Brussels Withdrawn
Brussels, Belgium, 1180
Investigator Site - Brussels Recruiting
Brussels, Belgium, 1200
Investigator Site - Charleroi Recruiting
Charleroi, Belgium, 6000
Investigator Site - Edegem Recruiting
Edegem, Belgium, 2650
Investigator Site - Liege Recruiting
Liège, Belgium, 4000
Investigator Site - Namur Recruiting
Namur, Belgium, 5000
Investigator Site - Sint-Niklaas Recruiting
Sint-Niklaas, Belgium, 9100
Investigator Site - Woluwe- Saint-Lambert Recruiting
Woluwe-Saint-Lambert, Belgium, 1200
Canada, Quebec
Investigator Site - Montreal Recruiting
Montréal, Quebec, Canada, H4A 3J1
Czechia
Investigator Site - Praha Withdrawn
Praha, Czechia, 14044
France
Investigator Site - Grenoble Recruiting
Grenoble, France, 38700
Investigator Site - Le Mans Recruiting
Le Mans, France, 72000
Investigator Site - Nimes Recruiting
Nîmes, France, 30029
Investigator Site - Paris Recruiting
Paris, France, 75248
Investigator Site - Paris Recruiting
Paris, France, 75475
Investigator Site - Rennes Recruiting
Rennes, France, 35042
Investigator Site - Rouen Recruiting
Rouen, France, 76038
Investigator Site - Saint-Cloud Withdrawn
Saint-Cloud, France, 92210
Investigator Site - Strasbourg Recruiting
Strasbourg, France, 67091
Investigator Site - Toulouse Withdrawn
Toulouse, France, 31052
Israel
Investigator Site - Be'er Ya'aqov Withdrawn
Be'er Ya'aqov, Israel, 70300
Investigator Site - Beersheba Recruiting
Beersheba, Israel, 84101
Investigator Site - Haifa Recruiting
Haifa, Israel, 31096
Investigator Site - Jerusalem Withdrawn
Jerusalem, Israel, 91120
Investigator Site - Tel Aviv Recruiting
Tel Aviv, Israel, 64239
Investigator Site - Zerifin Recruiting
Zerifin, Israel, 70300
Italy
Investigator Site - Grosetto Recruiting
Grosseto, Italy, 58100
Investigator Site - Milano Recruiting
Milano, Italy, 20141
Investigator Site - Milan Recruiting
Milan, Italy, 20132
Investigator Site - Napoli Recruiting
Napoli, Italy, 80131
Investigator Site - Roma Recruiting
Roma, Italy, 144
New Zealand
Investigator Site - Christchurch Withdrawn
Christchurch, New Zealand, 8011
Portugal
Investigator Site - Lisboa Recruiting
Lisboa, Portugal, 1649-035
Investigator Site - Lisbon Recruiting
Lisbon, Portugal, 1400-038
Investigator Site - Porto Recruiting
Porto, Portugal, 4200-072
Spain
Investigator Site - San Sebastián Withdrawn
San Sebastián, Gipuzkoa, Spain, 20014
Investigator Site - Barcelona Recruiting
Barcelona, Spain, 8023
Investigator Site - Barcelona Recruiting
Barcelona, Spain, 8035
Investigator Site - Granollers Recruiting
Granollers, Spain, 08402
Investigator Site - Jaen Recruiting
Jaén, Spain, 23007
Investigator Site - Madrid Withdrawn
Madrid, Spain, 28034
Investigator Site - Madrid Recruiting
Madrid, Spain, 28040
Investigator Site - Santa Cruz de Tenerife Recruiting
Santa Cruz de Tenerife, Spain, 38320
Investigator Site - Sevilla Recruiting
Sevilla, Spain, 41009
Investigator Site - Sevilla Recruiting
Sevilla, Spain, 41013
United Kingdom
Investigator Site - Bradford Recruiting
Bradford, United Kingdom, BD7 1DP
Investigator Site - Manchester Recruiting
Manchester, United Kingdom, M20 4BX
Investigator Site - Nottingham Recruiting
Nottingham, United Kingdom, NG5 1PB
Sponsors and Collaborators
Nektar Therapeutics

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Nektar Therapeutics
ClinicalTrials.gov Identifier: NCT02915744     History of Changes
Other Study ID Numbers: 15-102-14
First Posted: September 27, 2016    Key Record Dates
Last Update Posted: March 6, 2019
Last Verified: March 2019

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

Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasm Metastasis
Neoplasms, Second Primary
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Paclitaxel
Vinorelbine
Docetaxel
Albumin-Bound Paclitaxel
Gemcitabine
Capecitabine
Taxane
Etirinotecan pegol
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