A Safety and Efficacy Study of Farletuzumab in Participants With Adenocarcinoma of the Lung
- Conditions
- Adenocarcinoma of the Lung
- Interventions
- Biological: FarletuzumabOther: Placebo
- Registration Number
- NCT01218516
- Lead Sponsor
- Morphotek
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 130
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Farletuzumab plus Chemotherapy Farletuzumab 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. Farletuzumab plus Chemotherapy Cisplatin 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. Farletuzumab plus Chemotherapy Paclitaxel 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. Placebo plus Chemotherapy Placebo 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. Placebo plus Chemotherapy Pemetrexed 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. Placebo plus Chemotherapy Cisplatin 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. Farletuzumab plus Chemotherapy Carboplatin 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. Farletuzumab plus Chemotherapy Pemetrexed 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. Placebo plus Chemotherapy Carboplatin 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. Placebo plus Chemotherapy Paclitaxel 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.
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) 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 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).
- Secondary Outcome Measures
Name Time Method Overall Response Rate (ORR) 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 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.
Duration of Response (DR) 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 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.
Overall Survival (OS) 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 OS was defined as the time (in months) from the date of randomization to the date of death, regardless of cause.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (SAEs) 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 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.
Trial Locations
- Locations (93)
Clinical Trials and Research Associates, Inc.
🇺🇸Montebello, California, United States
Medical Specialists of the Palm Beaches
🇺🇸Deerfield Beach, Florida, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Maryland Oncology Hematology, P.A.
🇺🇸Columbia, Maryland, United States
Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
Cancer Care Associates of Fresno Medical Group, Inc.
🇺🇸Fresno, California, United States
Moores University of California San Diego Cancer Center
🇺🇸La Jolla, California, United States
Detroit Clinical Research Center
🇺🇸Farmington Hills, Michigan, United States
Texas Oncology - Tyler
🇺🇸Tyler, Texas, United States
Rockwood Cancer Treatment Center
🇺🇸Spokane, Washington, United States
Southern Medical Day Oncology Care Centre
🇦🇺Wollongong, New South Wales, Australia
Frankston Hospital, Oncology Day Unit
🇦🇺Frankston, Victoria, Australia
Epworth Healthcare
🇦🇺Richmond, Victoria, Australia
Cancer Team Bellin Health
🇺🇸Green Bay, Wisconsin, United States
Asklepios Fachkliniken München-Gauting
🇩🇪Gauting, Bayern, Germany
Jewish General Hospital
🇨🇦Montréal, Quebec, Canada
Johannes-Wesling-Klinikum Minden
🇩🇪Minden, Nordrhein-westfalen, Germany
Delta Hematology Oncology Associates, PC
🇺🇸Portsmouth, Virginia, United States
Grand River Regional Cancer Centre
🇨🇦Kitchener, Ontario, Canada
Royal Adelaide Hospital, Cancer Centre
🇦🇺Adelaide, South Australia, Australia
Hospital Germans Trías i Pujol
🇪🇸Barcelona, Spain
Queens Hospital Center
🇺🇸Jamaica, New York, United States
Krankenhaus Nordwest GmbH
🇩🇪Frankfurt am Main, Hessen, Germany
Medical Oncology Associates, PS
🇺🇸Spokane, Washington, United States
Box Hill Hospital
🇦🇺Box Hill, Victoria, Australia
Universitätsklinikum Heidelberg
🇩🇪Heidelberg, Baden-wuerttemberg, Germany
Virginia Mason Medical Center
🇺🇸Seattle, Washington, United States
Lyell McEwin Hospital
🇦🇺Elizabeth Vale, South Australia, Australia
The Queen Elizabeth Hospital
🇦🇺Woodville South, South Australia, Australia
Klinik Löwenstein gGmbH
🇩🇪Löwenstein, Baden-wuerttemberg, Germany
Asklepios Klinik Harburg
🇩🇪Hamburg, Germany
Hospital General Vall d'Hebron, Barcelona
🇪🇸Barcelona, Spain
Fundación Jiménez Díaz
🇪🇸Madrid, Spain
Istituto Nazionale per la Ricerca sul Cancro
🇮🇹Genova, Italy
A.O. Seconda Università degli Studi di Napoli
🇮🇹Napoli, Italy
Hospital Regional Carlos Haya
🇪🇸Málaga, Malaga, Spain
Städtisches Krankenhaus Martha-Maria Halle Dölau gGmbH
🇩🇪Halle, Sachsen-anhalt, Germany
Cancer Research Center n.a. N.N. Blokhin
🇷🇺Moscow, Russian Federation
Glendale Adventist Medical Center
🇺🇸Los Angeles, California, United States
Englewood Hospital and Medical Center
🇺🇸Englewood, New Jersey, United States
Pacific Hematology Oncology Associates
🇺🇸San Francisco, California, United States
Tennessee Oncology, PLLC
🇺🇸Nashville, Tennessee, United States
Houston Cancer Institute
🇺🇸Houston, Texas, United States
Rocky Mountain Cancer Centers, LLP
🇺🇸Denver, Colorado, United States
Flinders Medical Centre, Dept. of Oncology
🇦🇺Bedford Park, South Australia, Australia
HELIOS Klinikum Emil von Behring
🇩🇪Berlin, Germany
City Oncology Hospital # 62
🇷🇺Moscow, Russian Federation
Hospital Clinic i Provincial de Barcelona
🇪🇸Barcelona, Spain
National Cancer Institute
🇺🇸Bethesda, Maryland, United States
Texas Oncology - Plano East
🇺🇸Plano, Texas, United States
Wilshire Medical Oncology Group
🇺🇸La Verne, California, United States
California Cancer Care, Inc.
🇺🇸Greenbrae, California, United States
Ironwood Cancer and Research Center
🇺🇸Chandler, Arizona, United States
Arizona Center for Hematology Oncology
🇺🇸Glendale, Arizona, United States
Medical Oncology Hematology
🇺🇸Gilroy, California, United States
Florida Cancer Institute-New Hope
🇺🇸New Port Richey, Florida, United States
Ocala Oncology Center, PL
🇺🇸Ocala, Florida, United States
Center for Hematology-Oncology
🇺🇸Boca Raton, Florida, United States
North Country Oncology-Hematology
🇺🇸Oceanside, California, United States
Cancer Care of North Florida
🇺🇸Lake City, Florida, United States
Broward General Medical Center
🇺🇸Fort Lauderdale, Florida, United States
Hematology Oncology Associates, P.C.
🇺🇸Stamford, Connecticut, United States
Central Coast Medical Oncology
🇺🇸Santa Maria, California, United States
The Community Hospital
🇺🇸Munster, Indiana, United States
Christus Saint Frances, Cabrini Hospital, Cabrini Cancer Center
🇺🇸Alexandria, Louisiana, United States
Baptist Health System, Inc.
🇺🇸Lexington, Kentucky, United States
Deaconess Clinic Downtown
🇺🇸Evansville, Indiana, United States
Kentucky Cancer Center
🇺🇸Hazard, Kentucky, United States
University Hematology Oncology, Inc.
🇺🇸Centralia, Illinois, United States
Hematology and Oncology Specialists, LLC
🇺🇸Metairie, Louisiana, United States
St. Luke's Cancer Center Associates
🇺🇸Bethlehem, Pennsylvania, United States
Berkshire Hematology Oncology, PC
🇺🇸Pittsfield, Massachusetts, United States
Willamette Valley Cancer Institute and Research Center
🇺🇸Eugene, Oregon, United States
Syracuse Veterns Affairs Medical Center
🇺🇸Syracuse, New York, United States
Texas Oncology - Bedford
🇺🇸Bedford, Texas, United States
Gettysburg Cancer Center
🇺🇸Gettysburg, Pennsylvania, United States
Northwest Cancer Center
🇺🇸Sugar Land, Texas, United States
Texas Oncology - Waco
🇺🇸Waco, Texas, United States
University of Texas Medical Branch
🇺🇸Galveston, Texas, United States
Virginia Cancer Specialists, PC
🇺🇸Fairfax, Virginia, United States
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
The Tweed Hospital
🇦🇺Tweed Heads, New South Wales, Australia
Ospedale Unico Versilia
🇮🇹Lido di Camaiore, Lucca, Italy
Specjalistyczny Szpital im. Alfreda Sokolowskiego
🇵🇱Szczecin, Zachodniopomorskie, Poland
Azienda Ospedaliero-Univesitaria "San Luigi Gonzaga"
🇮🇹Orbassano, Torino, Italy
Centrum Onkologii - Instytut im. M. Sklodowskiej-Curie w Warszawie
🇵🇱Warszawa, Mazowieckie, Poland
Wojewódzki Szpital Zespolony im. L. Rydygiera w Toruniu Szpital Dzieciecy
🇵🇱Torun, Kujawsko-pomorskie, Poland
Republican Clinical Oncologic Dispensary of Ministry of health of Republic Tatarstan
🇷🇺Kazan, Tatarstan, Russian Federation
Providence Health System
🇺🇸Beverly Hills, California, United States
MD Anderson Cancer Center-Orlando
🇺🇸Orlando, Florida, United States
Royal Brisbane and Women's Hospital, Dept. of Medical Oncology
🇦🇺Brisbane, Queensland, Australia
Fremantle Hospital
🇦🇺Fremantle, Western Australia, Australia
Royal Victoria Hospital
🇨🇦Barrie, Ontario, Canada