Clinical trial NCT01104155: Eribulin Mesylate in Combination With Intermittent Erlotinib in Patients With Previously Treated, Advanced Non-Small Cell Lung Cancer
Official title: The Purpose of This Study is to Investigate Two Different Dose Regimens of Eribulin Mesylate in Combination With Intermittent Erlotinib in Patients With Previously Treated, Advanced Non-small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Keywords: NSCLC
Eribulin Mesylate
Erlotinib
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2010-04-15
Enrollment: 123
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion criteria:

* 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).

Exclusion criteria:

* 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
* Any history of or concomitant medical condition that, in the opinion of the Investigator, would compromise the subject's ability to safely complete the study
* Major surgery within 4 weeks before starting study treatment or scheduled for surgery during the projected course of the study

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: From date of first dose of study drug until, or up to the date of data cutoff (07 Apr 2011)
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: 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
measure: Progression-Free Survival (PFS)
timeFrame: 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
measure: Disease Control Rate (DCR)
timeFrame: 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
measure: Overall Survival (OS)
timeFrame: 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
Other outcomes:
Locations:
city: Bessemer
country: United States
state: Alabama
city: Birmingham
country: United States
state: Alabama
city: Beverly Hills
country: United States
state: California
city: La Jolla
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Boulder
country: United States
state: Colorado
city: Colorado Springs
country: United States
state: Colorado
city: Denver
country: United States
state: Colorado
city: Lakewood
country: United States
state: Colorado
city: Littleton
country: United States
state: Colorado
city: Lone Tree
country: United States
state: Colorado
city: Longmont
country: United States
state: Colorado
city: Parker
country: United States
state: Colorado
city: Thornton
country: United States
state: Colorado
city: Washington
country: United States
state: District of Columbia
city: Ocala
country: United States
state: Florida
city: Port Saint Lucie
country: United States
state: Florida
city: Kansas City
country: United States
state: Kansas
city: Overland Park
country: United States
state: Kansas
city: Shawnee Mission
country: United States
state: Kansas
city: Detroit
country: United States
state: Michigan
city: Columbia
country: United States
state: Missouri
city: Jefferson City
country: United States
state: Missouri
city: Kansas City
country: United States
state: Missouri
city: Lee's Summit
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Las Vegas
country: United States
state: Nevada
city: Elizabeth City
country: United States
state: North Carolina
city: Portland
country: United States
state: Oregon
city: Tualatin
country: United States
state: Oregon
city: Philadelphia
country: United States
state: Pennsylvania
city: East Providence
country: United States
state: Rhode Island
city: Dallas
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Garland
country: United States
state: Texas
city: Plano
country: United States
state: Texas
city: Arlington
country: United States
state: Virginia
city: Chesapeake
country: United States
state: Virginia
city: Fairfax
country: United States
state: Virginia
city: Gainesville
country: United States
state: Virginia
city: Hampton
country: United States
state: Virginia
city: Leesburg
country: United States
state: Virginia
city: Newport News
country: United States
state: Virginia
city: Norfolk
country: United States
state: Virginia
city: Virginia Beach
country: United States
state: Virginia
city: Williamsburg
country: United States
state: Virginia
city: Winchester
country: United States
state: Virginia
city: Woodbridge
country: United States
state: Virginia
city: Spokane
country: United States
state: Washington
city: Vancouver
country: United States
state: Washington
city: Hong Kong
country: Hong Kong
city: Goyang
country: Korea, Republic of
city: Gyeonggi-do
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Kuantan
country: Malaysia
state: Pahang
city: George town
country: Malaysia
city: Singapore
country: Singapore
city: Taichung
country: Taiwan
city: Tainan
country: Taiwan
city: Taipei
country: Taiwan
city: Bangkok
country: Thailand
city: Chiang Mai
country: Thailand
city: Lampang
country: Thailand
city: Songkhla
country: Thailand
Study officials:
References:
citation: 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.