Eribulin Mesylate in Combination With Intermittent Erlotinib in Patients With Previously Treated, Advanced Non-Small Cell Lung Cancer

NCT01104155 | Completed Phase 2 Results

• 1 other identifier: E7389-G000-205
• Study Type: interventional
• Target: 123
• Locations: 7 countries
• Sites: 64

Brief Summary

This is a Phase 2, multicenter, randomized study of two different dose regimens of eribulin mesylate in combination with intermittent erlotinib in patients with previously treated, advanced non-small cell lung cancer.

Conditions

Non-small Cell Lung Cancer

Keywords

NSCLC; Eribulin Mesylate; Erlotinib

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR was defined as the percentage of participants whose best overall response (BOR) was either a confirmed complete response (CR) or a partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria for target lesions assessed by computed tomography (CT) or magnetic resonance imaging (MRI) and based on investigator assessment. CRs and PRs had to be confirmed by a repeat assessment of response (CR or PR) separated by at least 4 weeks (28 days). CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to have a reduction in short axis to less than 10 millimeters. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR and the corresponding 95% two-sided confidence intervals (CI) were estimated for each treatment regimen using the Clopper-Pearson method for calculating the exact binomial CI. (CR + PR)

  From date of first dose of study drug until, or up to the date of data cutoff (07 Apr 2011)

Secondary Outcomes (4)

• Duration of Response (DOR)

  From date of first document CR or PR (whichever was recorded first) until first documentation of disease progression or death due to any cause, or up to data cutoff (31 May 2013) up to 3.25 years

• Progression-Free Survival (PFS)

  From date of first dose of study drug until documentation of disease progression or death from any cause (whichever occurred first), or up to data cutoff (31 May 2013) up to 3.25 years

• Disease Control Rate (DCR)

  From date of first dose of study drug until documentation of disease progression or death from any cause (whichever occurred first) or up to data cutoff (31 May 2013), up to approximately 3.25 years

• Overall Survival (OS)

  From date of first dose of study drug until date of death from any cause or up to data cutoff (31 May 2013), up to approximately 3.25 years

Study Arms (2)

eribulin mesylate, 21 day cycle

ACTIVE COMPARATOR

Drug: eribulin mesylate + erlotinib

eribulin mesylate, 28 day cycle

ACTIVE COMPARATOR

Drug: eribulin mesylate + erlotinib

Interventions

eribulin mesylate + erlotinib DRUG

21-day Regimen: Eribulin mesylate given at a dose of 2 mg/m2 as a 2-5 min intravenous (IV) bolus on Day 1 and 150 mg of erlotinib given orally once daily, one hour before or two hours after the ingestion of food, on Days 2-16 of a 21-day cycle.

eribulin mesylate, 21 day cycle

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed non-small cell lung cancer (NSCLC)
• At least one prior platinum-based doublet anti-cancer treatment for recurrent or advanced NSCLC
• Disease progression during or after the last anti-cancer therapy
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
• Serum creatinine less than or equal to 2.0 mg/dL or creatinine clearance 40 mL/min according to Cockcroft and Gault formula:
• Absolute neutrophil count greater than or equal to 1.5 x 10\^9/L, hemoglobin greater than or equal to 10 g/dL (can be corrected by growth factor or transfusion), and platelet count greater than or equal to 100 x 10\^9/L
• Total bilirubin less than or equal to 1.5 times the upper limit of normal (ULN) and alkaline phosphatase (AP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 3 times ULN (in the case of liver metastases less than or equal to 5 times ULN). In case AP is greater than 3 times ULN (in absence of liver metastases) or greater than 5 times ULN (in presence of liver metastases) AND subject also is known to have bone metastases, the liver specific AP must be separated from the total and used to assess the liver function instead of the total AP.
• At least one lesion of greater than or equal to 1.5 cm in longest diameter for non-lymph nodes or greater than or equal to 1.5 cm in shortest diameter for lymph nodes which is serially measurable according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.17
• Males and females, age greater than or equal to 18 years
• Provide written informed consent
• Are willing and able to comply with all aspects of the protocol
• Females of childbearing potential must have a negative serum beta-human chorionic gonadotropin (Beta-hCG) at Visit 1 (Screening) and a negative urine pregnancy test prior to starting study drug (Visit 2). Female subjects of childbearing potential must agree to be abstinent or to use highly effective methods of contraception (eg, condom + spermicide, condom + diaphragm with spermicide, intrauterine device (IUD), or have a vasectomised partner) having starting for at least one menstrual cycle prior to starting study drugs and throughout the entire study period and for 30 days (longer if appropriate) after the last dose of study drug. Those women using hormonal contraceptives must also be using an additional approved method of contraception (as described previously). Perimenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
• Male subjects who are not abstinent or have not undergone a successful vasectomy, who are partners of women of childbearing potential must use, or their partners must use a highly effective method of contraception (eg, condom + spermicide, condom + diaphragm with spermicide, IUD) starting for at least one menstrual cycle prior to starting study drugs and throughout the entire study period and for 30 days (longer if appropriate) after the last dose of study drug. Those with partners using hormonal contraceptives must also be using an additional approved method of contraception (as described previously).

You may not qualify if:

• Prior therapy with eribulin or an tyrosine kinase inhibitor of the epidermal growth factor receptor
• Subjects with brain or subdural metastases are not eligible, unless they have completed local therapy and have discontinued steroids for this indication for greater than or equal to 4 weeks before starting study treatment. Symptoms attributed to brain metastases must be stable for greater than or equal to 4 weeks before starting study treatment; radiographic stability should be determined by comparing contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) brain scan performed during screening to a prior scan performed 4 weeks earlier.
• Existing anti-cancer therapy-related toxicities of grade greater than or equal to 2, other than any grade of alopecia or grade less than or equal to 2 neuropathy, which are acceptable
• Current smokers who will not stop smoking one week prior to treatment and during the study
• History of congestive heart failure with New York Heart Association (NYHA) Grade greater than II, unstable angina, myocardial infarction within the past 6 months, serious cardiac arrhythmia
• Electrocardiogram with QTc interval greater than or equal to 500 msec based upon Bazett's formula (QTcB)
• Females who are pregnant (positive Beta-hCG test) or breastfeeding
• Subject with hypersensitivity to eribulin and /or erlotinib or any of the excipients
• Presence of a progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors
• Subjects who are known to be human immunodeficiency virus (HIV) positive, because the neutropenia caused by the study treatments may make such subjects particularly susceptible to infection
• Subjects with active viral hepatitis (A, B, or C) as demonstrated by positive serology
• Radiotherapy, chemotherapy, biological therapy or investigational agents within 2 weeks prior to start of study treatment
• Meningeal carcinomatosis
• History of drug or alcohol dependency or abuse within approximately the last 2 years
• Medically unfit to receive the study drug or unsuitable for any other reason according to investigator judgment

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (64)

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Bessemer, Alabama, United States

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Birmingham, Alabama, United States

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Beverly Hills, California, United States

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La Jolla, California, United States

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Aurora, Colorado, United States

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Boulder, Colorado, United States

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Colorado Springs, Colorado, United States

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Denver, Colorado, United States

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Lakewood, Colorado, United States

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Littleton, Colorado, United States

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Lone Tree, Colorado, United States

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Longmont, Colorado, United States

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Parker, Colorado, United States

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Thornton, Colorado, United States

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Washington D.C., District of Columbia, United States

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Ocala, Florida, United States

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Port Saint Lucie, Florida, United States

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Kansas City, Kansas, United States

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Overland Park, Kansas, United States

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Shawnee Mission, Kansas, United States

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Detroit, Michigan, United States

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Columbia, Missouri, United States

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Jefferson City, Missouri, United States

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Kansas City, Missouri, United States

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Lee's Summit, Missouri, United States

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St Louis, Missouri, United States

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Las Vegas, Nevada, United States

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Elizabeth City, North Carolina, United States

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Portland, Oregon, United States

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Tualatin, Oregon, United States

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Philadelphia, Pennsylvania, United States

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East Providence, Rhode Island, United States

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Dallas, Texas, United States

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Fort Worth, Texas, United States

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Garland, Texas, United States

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Plano, Texas, United States

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Arlington, Virginia, United States

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Chesapeake, Virginia, United States

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Fairfax, Virginia, United States

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Gainesville, Virginia, United States

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Hampton, Virginia, United States

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Leesburg, Virginia, United States

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Newport News, Virginia, United States

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Norfolk, Virginia, United States

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Virginia Beach, Virginia, United States

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Williamsburg, Virginia, United States

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Winchester, Virginia, United States

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Woodbridge, Virginia, United States

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Spokane, Washington, United States

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Vancouver, Washington, United States

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Hong Kong, Hong Kong

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Kuantan, Pahang, Malaysia

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George Town, Malaysia

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Singapore, Singapore

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Goyang, South Korea

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Gyeonggi-do, South Korea

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Seoul, South Korea

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Taichung, Taiwan

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Tainan, Taiwan

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Taipei, Taiwan

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Bangkok, Thailand

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Chiang Mai, Thailand

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Lampang, Thailand

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Songkhla, Thailand

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Related Publications (1)

• Mok TS, Geater SL, Iannotti N, Thongprasert S, Spira A, Smith D, Lee V, Lim WT, Reyderman L, Wang B, Gopalakrishna P, Garzon F, Xu L, Reynolds C. Randomized phase II study of two intercalated combinations of eribulin mesylate and erlotinib in patients with previously treated advanced non-small-cell lung cancer. Ann Oncol. 2014 Aug;25(8):1578-84. doi: 10.1093/annonc/mdu174. Epub 2014 May 14.

  PMID: 24827127 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

eribulin; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Eisai Medical Information
• Organization: Eisai Inc.

esi_oncmedinfo@eisai.com

1-888-422-4743

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2010
• First Posted: April 15, 2010
• Study Start: February 22, 2010
• Primary Completion: April 7, 2011
• Study Completion: January 18, 2017
• Last Updated: June 22, 2023
• Results First Posted: February 14, 2017

Record last verified: 2018-01

Locations

TW (3); TH (4); US (50); KR (3); HK (1); SG (1); MY (2)