A Randomized, Open-label, Multicenter, Phase 3 Study to Compare the Efficacy and Safety of Eribulin With Treatment of Physician's Choice in Subjects With Advanced Non-Small Cell Lung Cancer

This is a randomized, open-label, multicenter, Phase 3 study, comparing efficacy and safety of eribulin with TPC in subjects with advanced and disease progression following at least two prior regimens for advanced disease, which should have included a platinum-based regimen.

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer (NSCLC)
• Intervention / Treatment: Drug: Eribulin; Drug: TPC -Vinorelbine,Gemcitabine,Docetaxel, and Pemetrexed

• Study Type: Interventional
• Enrollment (Actual): 540
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Herston, Queensland, Australia
  • Victoria
    • Frankston, Victoria, Australia
• France
  • Bas Rhin
    • Strasbourg, Bas Rhin, France
  • Bouches-du-Rhone
    • Marseille Cedex 20, Bouches-du-Rhone, France
  • Bouches-duRhone
    • Marseille Cedex 9, Bouches-duRhone, France
  • Gironde
    • Bordeaux, Gironde, France
  • Haute Garonne
    • Toulouse Cedex 9, Haute Garonne, France
  • Haute Vienne
    • Limoges, Haute Vienne, France
  • Ille Et Vilaine
    • Rennes Cedex 9, Ille Et Vilaine, France
  • Loire Atlantique
    • Saint Herblain, Loire Atlantique, France
  • Nord
    • Lille, Nord, France
  • Paris
    • Paris Cedex 12, Paris, France
  • Rhone
    • Pierre Benite cedex, Rhone, France
  • Val De Marne
    • Villejuif cedex, Val De Marne, France
• Germany
  • Bayern
    • Aschaffenburg, Bayern, Germany
    • Gauting, Bayern, Germany
    • Muenchen, Bayern, Germany
  • Nordrhein Westfalen
    • Essen, Nordrhein Westfalen, Germany
    • Koeln, Nordrhein Westfalen, Germany
    • Recklinghausen, Nordrhein Westfalen, Germany
  • Rheinland Pfalz
    • Mainz, Rheinland Pfalz, Germany
  • Sachsen Anhalt
    • Halle, Sachsen Anhalt, Germany
• Hong Kong
  • Hong Kong, Hong Kong
• Italy
  • Cremona, Italy
  • Milano, Italy
  • Siena, Italy
  • Lucca
    • Lido di Camaiore, Lucca, Italy
  • Milano
    • Monza, Milano, Italy
  • Pordenone
    • Aviano, Pordenone, Italy
• Japan
  • Kitaadachi-gun, Japan
  • Aichi-Ken
    • Nagoya-shi, Aichi-Ken, Japan
  • Chiba-Ken
    • Kashiwa-shi, Chiba-Ken, Japan
  • Fukuoka-Ken
    • Fukuoka-shi, Fukuoka-Ken, Japan
  • Hiroshima-Ken
    • Hiroshima-shi, Hiroshima-Ken, Japan
  • Hokkaido
    • Sapporo-shi, Hokkaido, Japan
  • Hygo-Ken
    • Kobe-shi, Hygo-Ken, Japan
  • Hyogo-ken
    • Akashi-shi, Hyogo-ken, Japan
  • Miyagi-Ken
    • Sendai-shi, Miyagi-Ken, Japan
  • Nigata-Ken
    • Nigata-shi, Nigata-Ken, Japan
  • Okayama-Ken
    • Kurashiki-shi, Okayama-Ken, Japan
  • Osaka-Fu
    • Habinko-shi, Osaka-Fu, Japan
    • Osaka-shi, Osaka-Fu, Japan
    • Osakasayama-shi, Osaka-Fu, Japan
  • Shizuoka-Ken
    • Sunto-gun, Shizuoka-Ken, Japan
  • Tokyo-To
    • Koto-ku, Tokyo-To, Japan
  • Tokyo-to
    • Chuo-ku, Tokyo-to, Japan
  • Yamaguchi-Ken
    • Ube-shi, Yamaguchi-Ken, Japan
• Korea, Republic of
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, Korea, Republic of
    • Suwon, Gyeonggi-do, Korea, Republic of
  • Korea
    • Seoul, Korea, Korea, Republic of
• Poland
  • Gdansk, Poland
  • Mrozy, Poland
  • Otwock, Poland
  • Sczedin, Poland
  • Warsazawa, Poland
• Russian Federation
  • Barnaul, Russian Federation
  • Novosibirsk, Russian Federation
  • Saint Petersburg, Russian Federation
• Singapore
  • Singapore, Singapore
• Spain
  • Barcelona, Spain
  • Madrid, Spain
  • Barcelona
    • Sabadell, Barcelona, Spain
    • Terrassa, Barcelona, Spain
  • Navarra
    • Pamplona, Navarra, Spain
• Taiwan
  • Taichung, Taiwan
  • Tainan, Taiwan
  • Taipei, Taiwan
  • Taipei City, Taiwan
• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom
  • Surrey
    • Sutton, Surrey, United Kingdom
• United States
  • California
    • Los Angeles, California, United States
    • Pleasant Hill, California, United States
    • San Diego, California, United States
  • Colorado
    • Aurora, Colorado, United States
  • District of Columbia
    • Washington, District of Columbia, United States
  • Florida
    • Port Saint Lucie, Florida, United States
  • Illinois
    • Decatur, Illinois, United States
  • Michigan
    • Southfield, Michigan, United States
  • New Hampshire
    • Lebanon, New Hampshire, United States
  • New York
    • Lake Success, New York, United States
  • Oregon
    • Portland, Oregon, United States
  • Washington
    • Spokane, Washington, United States
  • Wisconsin
    • Madison, Wisconsin, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion:

Subjects must meet all of the following criteria to be included in this study:

1. Histologically or cytologically confirmed diagnosis of NSCLC.
2. Documented evidence of advanced NSCLC not amenable to surgery or radiotherapy.
3. Confirmation of the presence or absence of EGFR mutations prior to study enrolment in all subjects.
4. Subjects must have received at least two prior regimens for advanced NSCLC, which should have included a platinum-based regimen and, in all subjects with tumors harbouring EGFR mutations, an EGFR TKI.
5. Radiographic evidence of disease progression on, or after, the last anti-cancer regimen prior to study entry.
6. Presence of measurable disease.
7. ECOG performance status of 0, 1, or 2.
8. Adequate bone marrow
9. Adequate renal function.
10. Adequate liver function.
11. Female subjects of child-bearing potential must agree to use two forms of highly effective contraception.
12. Male subjects and their female partners who are of child-bearing potential must agree to use two forms of highly effective contraception.
13. Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol.
14. Males or females aged at least 18 years (or any age greater than 18 years as determined by country legislation) at the time of informed consent.

Exclusion:

Subjects who meet any of the following criteria will be excluded from this study:

1. Subjects who have received any anti-cancer therapy within 14 days, or five half-lives of the drug (whichever is longer), prior to randomization.
2. Subjects who have not recovered from toxicities as a result of prior anti-cancer therapy to less than Grade 2.
3. Subjects who have previously been treated, or participated in a study with eribulin, whether treated with eribulin or not. The TPC option must not include the same agent which the subject received in a prior regimen.
4. Peripheral neuropathy more than CTCAE Grade 2.
5. Significant cardiovascular impairment.
6. Subjects with a high probability of Long QT Syndrome, or QTc interval >500 ms.
7. Subjects with brain or subdural metastases are not eligible, unless the metastases are asymptomatic and do not require treatment or have been adequately treated by local therapy.
8. Any serious concomitant illness.
9. Known HIV positive, or have an infection requiring treatment.
10. Any malignancy that required treatment, or has shown evidence of recurrence (except for NSCLC, non-melanoma skin cancer, or histologically confirmed complete excision of carcinoma in-situ) during the 5 years prior to study entry.
11. Female subjects must not be pregnant, and must not be breastfeeding.
12. Hypersensitivity to either HalB or HalB chemical derivatives or both, or to any of the excipients of the eribulin formulation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A	Drug: Eribulin; Administration of eribulin mesylate at a dose of 1.4 mg/m2 i.v. over 2 to 5 minutes on Days 1 and Day 8 of every cycle, where the duration of each cycle is 21 days.
Active Comparator: Arm B	Drug: TPC -Vinorelbine,Gemcitabine,Docetaxel, and Pemetrexed; Vinorelbine 30 mg/m2 i.v. on Day 1, every 7 days; Gemcitabine 1250 mg/m2 i.v. on Days 1 and 8, every 21 days; Docetaxel 75 mg/m2 i.v. on Day 1 every 21 days; Pemetrexed 500 mg/m2 i.v. on Day 1 every 21 days (nonsquamous histology only).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	The OS was defined as the time in months from the date of randomization to the date of death, regardless of cause. In the absence of confirmation of death, the participants were censored either at the date that participant was last known to be alive or the date of study cut-off, whichever was earlier. The two treatment arms were compared using the log-rank test, stratified by histology, TPC option, and geographic region; and the treatment difference between eribulin mesylate and TPC was tested at a significance level of 0.05 (2-sided). Kaplan-Meier (K-M) survival probabilities for each arm were plotted over time. The treatment effect was estimated by fitting a Cox Proportional Hazards model to the OS times including treatment arm as a factor and histology, TPC option and geographic region as strata.	Randomization (Day 1) until date of death from any cause, or 37 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) by Response Evaluation Criteria in Solid Tumors (RECIST)	PFS was defined as the time from the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first. The difference in PFS (based on the tumor response evaluation as determined by the investigator) between eribulin mesylate and TPC was evaluated using the log rank test, stratified by histology, TPC option, and geographic region, tested at an alpha level of 0.05 (2-sided). PFS censoring rules will be defined in the SAP and follow Federal Department of Agriculture (FDA) guidance.	Randomization (Day 1) until date of disease progression or death (whichever occurred first), or 37 months
Objective Response Rate (ORR)	The ORR was defined as the proportion of participants with best overall response of complete response (CR) or partial response (PR) per RECIST criteria. The ORR was estimated by study arm based on the tumor response evaluation as determined by the investigator, according to RECIST 1.1. Participants with unknown response were treated as non-responders. The statistical difference in ORR between treatment arms was evaluated using the Cochran-Mantel-Haenszel (CMH) chi-square test with histology, TPC option, and geographic region as strata, tested at an alpha level of 0.05 (2-sided). The 95 percent confidence interval (CI) was calculated using Clopper Pearson method.	Randomization (Day 1) to CR or PR

Collaborators and Investigators

• Sponsor: Eisai Inc.

Publications and helpful links

General Publications

• Katakami N, Felip E, Spigel DR, Kim JH, Olivo M, Guo M, Nokihara H, Yang JC, Iannotti N, Satouchi M, Barlesi F. A randomized, open-label, multicenter, phase 3 study to compare the efficacy and safety of eribulin to treatment of physician's choice in patients with advanced non-small cell lung cancer. Ann Oncol. 2017 Sep 1;28(9):2241-2247. doi: 10.1093/annonc/mdx284.

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2011
• Primary Completion (Actual): May 30, 2014
• Study Completion (Actual): May 2, 2016

Study Registration Dates

• First Submitted: October 13, 2011
• First Submitted That Met QC Criteria: October 17, 2011
• First Posted (Estimated): October 19, 2011

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 16, 2023
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Folic Acid Antagonists; Docetaxel; Vinorelbine; Pemetrexed; Gemcitabine
• Other Study ID Numbers: E7389-G000-302