Back to resultsA 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
Primary Purpose
Non-Small Cell Lung Cancer (NSCLC)
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Eribulin
TPC -Vinorelbine,Gemcitabine,Docetaxel, and Pemetrexed
Sponsored by
About this trial
This is an interventional treatment trial for Non-Small Cell Lung Cancer (NSCLC)
Eligibility Criteria
Inclusion:
Subjects must meet all of the following criteria to be included in this study:
- Histologically or cytologically confirmed diagnosis of NSCLC.
- Documented evidence of advanced NSCLC not amenable to surgery or radiotherapy.
- Confirmation of the presence or absence of EGFR mutations prior to study enrolment in all subjects.
- 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.
- Radiographic evidence of disease progression on, or after, the last anti-cancer regimen prior to study entry.
- Presence of measurable disease.
- ECOG performance status of 0, 1, or 2.
- Adequate bone marrow
- Adequate renal function.
- Adequate liver function.
- Female subjects of child-bearing potential must agree to use two forms of highly effective contraception.
- Male subjects and their female partners who are of child-bearing potential must agree to use two forms of highly effective contraception.
- Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol.
- 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:
- Subjects who have received any anti-cancer therapy within 14 days, or five half-lives of the drug (whichever is longer), prior to randomization.
- Subjects who have not recovered from toxicities as a result of prior anti-cancer therapy to less than Grade 2.
- 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.
- Peripheral neuropathy more than CTCAE Grade 2.
- Significant cardiovascular impairment.
- Subjects with a high probability of Long QT Syndrome, or QTc interval >500 ms.
- 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.
- Any serious concomitant illness.
- Known HIV positive, or have an infection requiring treatment.
- 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.
- Female subjects must not be pregnant, and must not be breastfeeding.
- Hypersensitivity to either HalB or HalB chemical derivatives or both, or to any of the excipients of the eribulin formulation.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Arm A
Arm B
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01454934
Brief Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
December 9, 2011 (Actual)
Primary Completion Date
May 30, 2014 (Actual)
Study Completion Date
May 2, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eisai Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Small Cell Lung Cancer (NSCLC)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
540 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A
Arm Type
Experimental
Arm Title
Arm B
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Eribulin
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
TPC -Vinorelbine,Gemcitabine,Docetaxel, and Pemetrexed
Intervention Description
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).
Primary Outcome Measure Information:
Title
Overall Survival (OS)
Description
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.
Time Frame
Randomization (Day 1) until date of death from any cause, or 37 months
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS) by Response Evaluation Criteria in Solid Tumors (RECIST)
Description
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.
Time Frame
Randomization (Day 1) until date of disease progression or death (whichever occurred first), or 37 months
Title
Objective Response Rate (ORR)
Description
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.
Time Frame
Randomization (Day 1) to CR or PR
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion:
Subjects must meet all of the following criteria to be included in this study:
Histologically or cytologically confirmed diagnosis of NSCLC.
Documented evidence of advanced NSCLC not amenable to surgery or radiotherapy.
Confirmation of the presence or absence of EGFR mutations prior to study enrolment in all subjects.
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.
Radiographic evidence of disease progression on, or after, the last anti-cancer regimen prior to study entry.
Presence of measurable disease.
ECOG performance status of 0, 1, or 2.
Adequate bone marrow
Adequate renal function.
Adequate liver function.
Female subjects of child-bearing potential must agree to use two forms of highly effective contraception.
Male subjects and their female partners who are of child-bearing potential must agree to use two forms of highly effective contraception.
Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol.
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:
Subjects who have received any anti-cancer therapy within 14 days, or five half-lives of the drug (whichever is longer), prior to randomization.
Subjects who have not recovered from toxicities as a result of prior anti-cancer therapy to less than Grade 2.
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.
Peripheral neuropathy more than CTCAE Grade 2.
Significant cardiovascular impairment.
Subjects with a high probability of Long QT Syndrome, or QTc interval >500 ms.
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.
Any serious concomitant illness.
Known HIV positive, or have an infection requiring treatment.
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.
Female subjects must not be pregnant, and must not be breastfeeding.
Hypersensitivity to either HalB or HalB chemical derivatives or both, or to any of the excipients of the eribulin formulation.
Facility Information:
City
Los Angeles
State/Province
California
Country
United States
City
Pleasant Hill
State/Province
California
Country
United States
City
San Diego
State/Province
California
Country
United States
City
Aurora
State/Province
Colorado
Country
United States
City
Washington
State/Province
District of Columbia
Country
United States
City
Port Saint Lucie
State/Province
Florida
Country
United States
City
Decatur
State/Province
Illinois
Country
United States
City
Southfield
State/Province
Michigan
Country
United States
City
Lebanon
State/Province
New Hampshire
Country
United States
City
Lake Success
State/Province
New York
Country
United States
City
Portland
State/Province
Oregon
Country
United States
City
Spokane
State/Province
Washington
Country
United States
City
Madison
State/Province
Wisconsin
Country
United States
City
Herston
State/Province
Queensland
Country
Australia
City
Frankston
State/Province
Victoria
Country
Australia
City
Strasbourg
State/Province
Bas Rhin
Country
France
City
Marseille Cedex 20
State/Province
Bouches-du-Rhone
Country
France
City
Marseille Cedex 9
State/Province
Bouches-duRhone
Country
France
City
Bordeaux
State/Province
Gironde
Country
France
City
Toulouse Cedex 9
State/Province
Haute Garonne
Country
France
City
Limoges
State/Province
Haute Vienne
Country
France
City
Rennes Cedex 9
State/Province
Ille Et Vilaine
Country
France
City
Saint Herblain
State/Province
Loire Atlantique
Country
France
City
Lille
State/Province
Nord
Country
France
City
Paris Cedex 12
State/Province
Paris
Country
France
City
Pierre Benite cedex
State/Province
Rhone
Country
France
City
Villejuif cedex
State/Province
Val De Marne
Country
France
City
Aschaffenburg
State/Province
Bayern
Country
Germany
City
Gauting
State/Province
Bayern
Country
Germany
City
Muenchen
State/Province
Bayern
Country
Germany
City
Essen
State/Province
Nordrhein Westfalen
Country
Germany
City
Koeln
State/Province
Nordrhein Westfalen
Country
Germany
City
Recklinghausen
State/Province
Nordrhein Westfalen
Country
Germany
City
Mainz
State/Province
Rheinland Pfalz
Country
Germany
City
Halle
State/Province
Sachsen Anhalt
Country
Germany
City
Hong Kong
Country
Hong Kong
City
Lido di Camaiore
State/Province
Lucca
Country
Italy
City
Monza
State/Province
Milano
Country
Italy
City
Aviano
State/Province
Pordenone
Country
Italy
City
Cremona
Country
Italy
City
Milano
Country
Italy
City
Siena
Country
Italy
City
Nagoya-shi
State/Province
Aichi-Ken
Country
Japan
City
Kashiwa-shi
State/Province
Chiba-Ken
Country
Japan
City
Fukuoka-shi
State/Province
Fukuoka-Ken
Country
Japan
City
Hiroshima-shi
State/Province
Hiroshima-Ken
Country
Japan
City
Sapporo-shi
State/Province
Hokkaido
Country
Japan
City
Kobe-shi
State/Province
Hygo-Ken
Country
Japan
City
Akashi-shi
State/Province
Hyogo-ken
Country
Japan
City
Sendai-shi
State/Province
Miyagi-Ken
Country
Japan
City
Nigata-shi
State/Province
Nigata-Ken
Country
Japan
City
Kurashiki-shi
State/Province
Okayama-Ken
Country
Japan
City
Habinko-shi
State/Province
Osaka-Fu
Country
Japan
City
Osaka-shi
State/Province
Osaka-Fu
Country
Japan
City
Osakasayama-shi
State/Province
Osaka-Fu
Country
Japan
City
Sunto-gun
State/Province
Shizuoka-Ken
Country
Japan
City
Chuo-ku
State/Province
Tokyo-to
Country
Japan
City
Koto-ku
State/Province
Tokyo-To
Country
Japan
City
Ube-shi
State/Province
Yamaguchi-Ken
Country
Japan
City
Kitaadachi-gun
Country
Japan
City
Seongnam-si
State/Province
Gyeonggi-do
Country
Korea, Republic of
City
Suwon
State/Province
Gyeonggi-do
Country
Korea, Republic of
City
Seoul
State/Province
Korea
Country
Korea, Republic of
City
Gdansk
Country
Poland
City
Mrozy
Country
Poland
City
Otwock
Country
Poland
City
Sczedin
Country
Poland
City
Warsazawa
Country
Poland
City
Barnaul
Country
Russian Federation
City
Novosibirsk
Country
Russian Federation
City
Saint Petersburg
Country
Russian Federation
City
Singapore
Country
Singapore
City
Sabadell
State/Province
Barcelona
Country
Spain
City
Terrassa
State/Province
Barcelona
Country
Spain
City
Pamplona
State/Province
Navarra
Country
Spain
City
Barcelona
Country
Spain
City
Madrid
Country
Spain
City
Taichung
Country
Taiwan
City
Tainan
Country
Taiwan
City
Taipei City
Country
Taiwan
City
Taipei
Country
Taiwan
City
London
State/Province
Greater London
Country
United Kingdom
City
Manchester
State/Province
Greater Manchester
Country
United Kingdom
City
Sutton
State/Province
Surrey
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
28911085
Citation
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.
Results Reference
derived
Learn more about this trial
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
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