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

NCT ID: NCT02915744

Last Updated: 2023-04-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 178 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-30
• Study Completion Date: 2020-07-31

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).

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 Overall Survival (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.

Conditions

Metastasis; Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

NKTR-102

Intervention Type: DRUG

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.

Group Type: ACTIVE_COMPARATOR

Eribulin

Intervention Type: DRUG

Ixabepilone

Intervention Type: DRUG

Vinorelbine

Intervention Type: DRUG

Gemcitabine

Intervention Type: DRUG

Paclitaxel

Intervention Type: DRUG

Docetaxel

Intervention Type: DRUG

Nab-paclitaxel

Intervention Type: DRUG

Interventions

NKTR-102

Intervention Type: DRUG

Eribulin

Intervention Type: DRUG

Ixabepilone

Intervention Type: DRUG

Vinorelbine

Intervention Type: DRUG

Gemcitabine

Intervention Type: DRUG

Paclitaxel

Intervention Type: DRUG

Docetaxel

Intervention Type: DRUG

Nab-paclitaxel

Intervention Type: DRUG

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.
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nektar Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Investigator Site - Tucson

Tucson, Arizona, United States

Investigator Site - Orange

Orange, California, United States

Investigator Site - San Francisco

San Francisco, California, United States

Investigator Site - Miami

Miami, Florida, United States

Investigator Site - Plantation

Plantation, Florida, United States

Investigator Site - West Palm Beach

West Palm Beach, Florida, United States

Investigator Site - Athens

Athens, Georgia, United States

Investigator Site - Baltimore

Baltimore, Maryland, United States

Investigator Site - Boston

Boston, Massachusetts, United States

Investigator Site - Minneapolis

Minneapolis, Minnesota, United States

Investigator Site - Saint Louis

St Louis, Missouri, United States

Investigator Site - New York

New York, New York, United States

Investigator Site - Chapel Hill

Chapel Hill, North Carolina, United States

Investigator Site - Columbus

Columbus, Ohio, United States

Investigator Site - Germantown

Germantown, Tennessee, United States

Investigator Site - Fort Worth

Fort Worth, Texas, United States

Investigator Site - Houston

Houston, Texas, United States

Investigator Site - Salt Lake City

Salt Lake City, Utah, United States

Investigator Site - Seattle

Seattle, Washington, United States

Investigatory Site - Albury

Albury, New South Wales, Australia

Investigator Site - Darlinghurst

Darlinghurst, New South Wales, Australia

Investigator Site - Wollongong

Wollongong, New South Wales, Australia

Investigator Site - Subiaco

Subiaco, Western Australia, Australia

Investigator Site - Box Hill

Box Hill, , Australia

Investigator Site - Nedlands

Nedlands, , Australia

Investigator Site - Brussels

Brussels, , Belgium

Investigator Site - Brussels

Brussels, , Belgium

Investigator Site - Brussels

Brussels, , Belgium

Investigator Site - Charleroi

Charleroi, , Belgium

Investigator Site - Edegem

Edegem, , Belgium

Investigator Site - Liege

Liège, , Belgium

Investigator Site - Woluwe- Saint-Lambert

Woluwe-Saint-Lambert, , Belgium

Investigator Site - Montreal

Montreal, Quebec, Canada

Investigator Site - Le Mans

Le Mans, , France

Investigator Site - Nimes

Nîmes, , France

Investigator Site - Paris

Paris, , France

Investigator Site - Rennes

Rennes, , France

Investigator Site - Rouen

Rouen, , France

Investigator Site - Strasbourg

Strasbourg, , France

Investigator Site - Beersheba

Beersheba, , Israel

Investigator Site - Haifa

Haifa, , Israel

Investigator Site - Tel Aviv

Tel Aviv, , Israel

Investigator Site - Milan

Milan, , Italy

Investigator Site - Milano

Milan, , Italy

Investigator Site - Napoli

Napoli, , Italy

Investigator Site - Roma

Roma, , Italy

Investigator Site - Lisboa

Lisbon, , Portugal

Investigator Site - Porto

Porto, , Portugal

Investigator Site - Barcelona

Barcelona, , Spain

Investigator Site - Barcelona

Barcelona, , Spain

Investigator Site - Madrid

Madrid, , Spain

Investigator Site - Santa Cruz de Tenerife

Santa Cruz de Tenerife, , Spain

Investigator Site - Sevilla

Seville, , Spain

Investigator Site - Bradford

Bradford, , United Kingdom

Investigator Site - Manchester

Manchester, , United Kingdom

Investigator Site - Nottingham

Nottingham, , United Kingdom

Countries

United States; Australia; Belgium; Canada; France; Israel; Italy; Portugal; Spain; United Kingdom

References

Tripathy D, Tolaney SM, Seidman AD, Anders CK, Ibrahim N, Rugo HS, Twelves C, Dieras V, Muller V, Du Y, Currie SL, Hoch U, Tagliaferri M, Hannah AL, Cortes J; ATTAIN Investigators. Treatment With Etirinotecan Pegol for Patients With Metastatic Breast Cancer and Brain Metastases: Final Results From the Phase 3 ATTAIN Randomized Clinical Trial. JAMA Oncol. 2022 Jul 1;8(7):1047-1052. doi: 10.1001/jamaoncol.2022.0514.

Reference Type: DERIVED

PMID: 35552364 (View on PubMed)

Tripathy D, Tolaney SM, Seidman AD, Anders CK, Ibrahim N, Rugo HS, Twelves C, Dieras V, Muller V, Tagliaferri M, Hannah AL, Cortes J. ATTAIN: Phase III study of etirinotecan pegol versus treatment of physician's choice in patients with metastatic breast cancer and brain metastases. Future Oncol. 2019 Jul;15(19):2211-2225. doi: 10.2217/fon-2019-0180. Epub 2019 May 10.

Reference Type: DERIVED

PMID: 31074641 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

15-102-14

Identifier Type: -

Identifier Source: org_study_id