A Safety and Efficacy Study of Farletuzumab in Participants With Adenocarcinoma of the Lung

A Randomized, Double-Blind, Placebo-Controlled, Study of the Safety and Efficacy of Farletuzumab in Combination With a Platinum-Containing Doublet in Chemotherapy-Naive Subjects With Stage IV Adenocarcinoma of the Lung (FLAIR)

The primary objective of this study is to compare the effect of farletuzumab versus placebo in combination with either a platinum agent (carboplatin) with paclitaxel or a platinum agent (carboplatin or cisplatin) with pemetrexed followed by farletuzumab or placebo on investigator-assessed progression free survival (PFS) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 or definitive clinical disease progression (eg, new occurrence of positive fluid cytology) in chemotherapy naive participants with folate receptoralpha (FRA)-expressing Stage IV adenocarcinoma of the lung.

Study Overview

• Status: Completed
• Conditions: Adenocarcinoma of the Lung
• Intervention / Treatment: Biological: Farletuzumab; Drug: Carboplatin; Drug: Paclitaxel; Drug: Pemetrexed; Drug: Cisplatin; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Tweed Heads, New South Wales, Australia, 2485
      • The Tweed Hospital
    • Wollongong, New South Wales, Australia, 2500
      • Southern Medical Day Oncology Care Centre
  • Queensland
    • Brisbane, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital, Dept. of Medical Oncology
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital, Cancer Centre
    • Bedford Park, South Australia, Australia, 5042
      • Flinders Medical Centre, Dept. of Oncology
    • Elizabeth Vale, South Australia, Australia, 5112
      • Lyell McEwin Hospital
    • Woodville South, South Australia, Australia, 5011
      • The Queen Elizabeth Hospital
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Box Hill Hospital
    • Frankston, Victoria, Australia, 3199
      • Frankston Hospital, Oncology Day Unit
    • Richmond, Victoria, Australia, 3002
      • Epworth Healthcare
  • Western Australia
    • Fremantle, Western Australia, Australia, 6160
      • Fremantle Hospital
• Canada
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Royal Victoria Hospital
    • Kitchener, Ontario, Canada, N2G 1G3
      • Grand River Regional Cancer Centre
    • Toronto, Ontario, Canada, MSG 2L7
      • Princess Margaret Hospital
  • Quebec
    • Montréal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
• Germany
  • Berlin, Germany, 14165
    • Helios Klinikum Emil Von Behring
  • Hamburg, Germany, 21075
    • Asklepios Klinik Harburg
  • Baden-wuerttemberg
    • Heidelberg, Baden-wuerttemberg, Germany, 69126
      • Universitätsklinikum Heidelberg
    • Löwenstein, Baden-wuerttemberg, Germany, 74245
      • Klinik Löwenstein gGmbH
  • Bayern
    • Gauting, Bayern, Germany, 82131
      • Asklepios Fachkliniken München-Gauting
  • Hessen
    • Frankfurt am Main, Hessen, Germany, 60488
      • Krankenhaus Nordwest GmbH
  • Nordrhein-westfalen
    • Minden, Nordrhein-westfalen, Germany, 32429
      • Johannes-Wesling-Klinikum Minden
  • Sachsen-anhalt
    • Halle, Sachsen-anhalt, Germany, 06120
      • Städtisches Krankenhaus Martha-Maria Halle Dölau gGmbH
• Italy
  • Genova, Italy, 16132
    • Istituto Nazionale per la Ricerca sul Cancro
  • Napoli, Italy, 80131
    • A.O. Seconda Università degli Studi di Napoli
  • Lucca
    • Lido di Camaiore, Lucca, Italy, 55043
      • Ospedale Unico Versilia
  • Torino
    • Orbassano, Torino, Italy, 10043
      • Azienda Ospedaliero-Univesitaria "San Luigi Gonzaga"
• Poland
  • Kujawsko-pomorskie
    • Torun, Kujawsko-pomorskie, Poland, 87-100
      • Wojewódzki Szpital Zespolony im. L. Rydygiera w Toruniu Szpital Dzieciecy
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 02-781
      • Centrum Onkologii - Instytut im. M. Sklodowskiej-Curie w Warszawie
  • Zachodniopomorskie
    • Szczecin, Zachodniopomorskie, Poland, 70-891
      • Specjalistyczny Szpital im. Alfreda Sokolowskiego
• Russian Federation
  • Moscow, Russian Federation, 115478
    • Cancer Research Center n.a. N.N. Blokhin
  • Moscow, Russian Federation, 143423
    • City Oncology Hospital # 62
  • Tatarstan
    • Kazan, Tatarstan, Russian Federation, 420029
      • Republican Clinical Oncologic Dispensary of Ministry of health of Republic Tatarstan
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial de Barcelona
  • Barcelona, Spain, 08916
    • Hospital Germans Trias i Pujol
  • Barcelona, Spain, 08035
    • Hospital General Vall d'Hebron, Barcelona
  • Madrid, Spain, 28040
    • Fundacion Jimenez Diaz
  • Malaga
    • Málaga, Malaga, Spain, 29010
      • Hospital Regional Carlos Haya
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Ironwood Cancer and Research Center
    • Glendale, Arizona, United States, 85306-4666
      • Arizona Center for Hematology Oncology
  • California
    • Beverly Hills, California, United States, 90210-5501
      • Providence Health System
    • Fresno, California, United States, 93720
      • Cancer Care Associates of Fresno Medical Group, Inc.
    • Gilroy, California, United States, 95020
      • Medical Oncology Hematology
    • Greenbrae, California, United States, 94904
      • California Cancer Care, Inc.
    • La Jolla, California, United States, 92093
      • Moores University of California San Diego Cancer Center
    • La Verne, California, United States, 91750
      • Wilshire Medical Oncology Group
    • Los Angeles, California, United States, 90025
      • Glendale Adventist Medical Center
    • Montebello, California, United States, 90640
      • Clinical Trials and Research Associates, Inc.
    • Oceanside, California, United States, 92056
      • North Country Oncology-Hematology
    • San Francisco, California, United States, 94115
      • Pacific Hematology Oncology Associates
    • Santa Maria, California, United States, 93454
      • Central Coast Medical Oncology
  • Colorado
    • Denver, Colorado, United States, 80218-1237
      • Rocky Mountain Cancer Centers, LLP
  • Connecticut
    • Stamford, Connecticut, United States, 06902-3628
      • Hematology Oncology Associates, P.C.
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Center for Hematology-Oncology
    • Deerfield Beach, Florida, United States, 33441
      • Medical Specialists of the Palm Beaches
    • Fort Lauderdale, Florida, United States, 33316
      • Broward General Medical Center
    • Lake City, Florida, United States, 32024
      • Cancer Care of North Florida
    • New Port Richey, Florida, United States, 34655
      • Florida Cancer Institute-New Hope
    • Ocala, Florida, United States, 34474
      • Ocala Oncology Center, PL
    • Orlando, Florida, United States, 32806
      • MD Anderson Cancer Center-Orlando
  • Illinois
    • Centralia, Illinois, United States, 62801
      • University Hematology Oncology, Inc.
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Indiana
    • Evansville, Indiana, United States, 47713
      • Deaconess Clinic Downtown
    • Munster, Indiana, United States, 46321
      • The Community Hospital
  • Kentucky
    • Hazard, Kentucky, United States, 41701
      • Kentucky Cancer Center
    • Lexington, Kentucky, United States, 40503
      • Baptist Health System, Inc.
  • Louisiana
    • Alexandria, Louisiana, United States, 71301
      • Christus Saint Frances, Cabrini Hospital, Cabrini Cancer Center
    • Metairie, Louisiana, United States, 70006
      • Hematology And Oncology Specialists, Llc
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Cancer Institute
    • Columbia, Maryland, United States, 21044
      • Maryland Oncology Hematology, P.A.
  • Massachusetts
    • Pittsfield, Massachusetts, United States, 01201
      • Berkshire Hematology Oncology, PC
  • Michigan
    • Farmington Hills, Michigan, United States, 48336
      • Detroit Clinical Research Center
  • New Jersey
    • Englewood, New Jersey, United States, 07631
      • Englewood Hospital and Medical Center
  • New York
    • Jamaica, New York, United States, 11432
      • Queens Hospital Center
    • Syracuse, New York, United States, 13210
      • Syracuse Veterns Affairs Medical Center
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Willamette Valley Cancer Institute and Research Center
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • St. Luke's Cancer Center Associates
    • Gettysburg, Pennsylvania, United States, 17325
      • Gettysburg Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology, PLLC
  • Texas
    • Bedford, Texas, United States, 76022
      • Texas Oncology - Bedford
    • Galveston, Texas, United States, 77555
      • University of Texas Medical Branch
    • Houston, Texas, United States, 77055
      • Houston Cancer Institute
    • Plano, Texas, United States, 75075-7787
      • Texas Oncology - Plano East
    • Sugar Land, Texas, United States, 77479
      • Northwest Cancer Center
    • Tyler, Texas, United States, 75702-8363
      • Texas Oncology - Tyler
    • Waco, Texas, United States, 76712
      • Texas Oncology - Waco
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists, PC
    • Portsmouth, Virginia, United States, 23704
      • Delta Hematology Oncology Associates, PC
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
    • Spokane, Washington, United States, 99208
      • Medical Oncology Associates, PS
    • Spokane, Washington, United States, 99204
      • Rockwood Cancer Treatment Center
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54313
      • Cancer Team Bellin Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the lung classified as stage IV
• Confirmed folate receptor-alpha (FRA) expression by immunohistochemistry (IHC)
• Measurable disease with at least one unidimensionally measurable lesion according to RECIST criteria version 1.1 by computed tomography (CT) or magnetic resonance imaging (MRI) scans (CT or MRI scans must have been performed within 30 days prior to the first dose of farletuzumab or placebo)
• Must have received no prior chemotherapy, radiation therapy or surgery with curative intent for adenocarcinoma of the lung

Exclusion Criteria:

• Participants who have had previous chemotherapy for adenocarcinoma of the lung
• Prior surgery with curative intent for adenocarcinoma of the lung
• Prior radiotherapy for adenocarcinoma of the lung. (Prior treatment with local radiotherapy for symptom control [i.e., palliative radiation with non-curative intent] is permitted)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Farletuzumab plus Chemotherapy; During Combination Therapy, farletuzumab will be given with a protocol-approved platinum doublet (either carboplatin/paclitaxel, carboplatin/pemetrexed, or cisplatin/pemetrexed) for at least 4, but not more than 6, cycles. Participants who experience clinical benefit from the Combination Therapy will enter the Monotherapy Phase and receive farletuzumab as monotherapy until disease progression.	Biological: Farletuzumab; Combination Therapy: Farletuzumab 7.5 mg/kg will be administered intravenously on Cycle 1, Week 1 and Cycle 1, Week 2 (loading dose). Beginning on Cycle 2, Week 1, farletuzumab (7.5 mg/kg) will be administered intravenously on Week 1 of all additional cycles. Monotherapy: Farletuzumab 7.5 mg/kg will be administered intravenously on Week 1 of every 3-week cycle until disease progression.; Other Names: MORAb-003; Drug: Carboplatin; Carboplatin will be administered intravenously to achieve area under the serum concentration-time curve of 5 to 6 mg/mL^min [AUC5-6].; Drug: Paclitaxel; Paclitaxel 200 mg/m^2 will be administered intravenously.; Drug: Pemetrexed; Pemetrexed 500 mg/m^2 will be administered intravenously.; Drug: Cisplatin; Cisplatin 75 mg/m^2 will be administered intravenously.
PLACEBO_COMPARATOR: Placebo plus Chemotherapy; During Combination Therapy, placebo will be given with a protocol-approved platinum doublet (either carboplatin/paclitaxel, carboplatin/pemetrexed, or cisplatin/pemetrexed) for at least 4, but not more than 6 cycles. Participants who experience clinical benefit from the Combination Therapy will enter the Monotherapy Phase and receive placebo as monotherapy until disease progression.	Drug: Carboplatin; Carboplatin will be administered intravenously to achieve area under the serum concentration-time curve of 5 to 6 mg/mL^min [AUC5-6].; Drug: Paclitaxel; Paclitaxel 200 mg/m^2 will be administered intravenously.; Drug: Pemetrexed; Pemetrexed 500 mg/m^2 will be administered intravenously.; Drug: Cisplatin; Cisplatin 75 mg/m^2 will be administered intravenously.; Other: Placebo; Combination Therapy: Placebo will be administered intravenously on Cycle 1, Week 1 and Cycle 1, Week 2 (loading dose). Beginning on Cycle 2, Week 1, placebo will be administered IV on Week 1 of all additional cycles. Monotherapy: Placebo will be administered intravenously on Week 1 of every 3-week cycle until disease progression.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	PFS was defined as the time from the date of randomization to the date of the first observation of investigator-assessed (radiology review) progression based on Response Evaluation Criteria In Solid Tumors (RECIST) v.1.1 or other protocol-approved measures of disease progression (e.g., new occurrence of positive fluid cytology, newly diagnosed evidence of disease progression from histologic samples, PET-positive metastases, or new bone or brain metastases), or date of death, whatever the cause. Disease progression as assessed by the investigator per RECIST v1.0 was defined as at least a 20% increase in sum of longest diameters (RECIST definition) compared to baseline (or lowest sum while on study if less than baseline), or any new lesions (measurable or nonmeasurable).	From date of first administration of study drug up to 6 month follow-up from randomization of the last participant, i.e., cut-off date 15 Dec 2012 for primary analysis and cut-off date of 1 Nov 2013 or up to approximately 28 months for final analysis

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	ORR, defined as the percentage of participants who had best overall response (BOR) of complete response (CR) or partial response (PR) as determined by investigator's radiologic assessments using RECIST 1.1 for target lesions and assessed by Magnetic resonance imaging (MRI) and computerized tomography (CT) scan (for double blind treatment period i.e. Randomization Phase). CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 mm. 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 = CR + PR.	From Day 1 until documented radiographic progression, other protocol-approved measures of disease progression, withdrawal by participant, death due to any cause, or cut-off date of 1 Nov 2013, i.e., up to approximately 28 months for final analysis
Duration of Response (DR)	DR was derived for those participants with objective evidence of CR or PR. DR was defined as the time (in months) from first documentation of objective response (CR or PR) to the first documentation of disease progression (ie, objective tumor progression as assessed by investigator's radiology review or other protocol-approved measures of disease progression) or death due to any cause. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	From the first documentation of objective response (CR or PR) to the first documentation of disease progression, death due to any cause, or cut-off date of 1 Nov 2013, i.e., up to approximately 28 months for final analysis
Overall Survival (OS)	OS was defined as the time (in months) from the date of randomization to the date of death, regardless of cause.	From the date of randomization to the date of death due to any cause or up to cut-off date of 1 Nov 2013 (up to approximately 28 months) for final analysis
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (SAEs)	An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered with an investigational product. A serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose; resulted in death, was life-threatening (i.e., the participant was at a risk of death at the time of the event; this did not include an event that hypothetically might have caused death if it had been more severe), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, or was a congenital abnormality/birth defect. In this study, TEAEs (defined as an AE that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) were assessed.	For each participant, from the first dose till 30 days after the last dose or cut-off date of 1 Nov 2013, i.e., up to approximately 28 months for final analysis

Collaborators and Investigators

• Sponsor: Morphotek

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 27, 2011
• Primary Completion (ACTUAL): December 15, 2012
• Study Completion (ACTUAL): November 1, 2013

Study Registration Dates

• First Submitted: October 7, 2010
• First Submitted That Met QC Criteria: October 7, 2010
• First Posted (ESTIMATE): October 11, 2010

Study Record Updates

• Last Update Posted (ACTUAL): August 20, 2020
• Last Update Submitted That Met QC Criteria: August 10, 2020
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Adenocarcinoma; Adenocarcinoma of Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Folic Acid Antagonists; Carboplatin; Paclitaxel; Cisplatin; Pemetrexed; Farletuzumab
• Other Study ID Numbers: MORAb-003-009; 2010-022229-13 (EUDRACT_NUMBER)