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

Adenocarcinoma of the Lung Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01218516
• Other study ID #: MORAb-003-009
• Secondary ID: 2010-022229-13
• Status: Completed
• Phase: Phase 2
• Start date: June 27, 2011
• Est. completion date: November 1, 2013

Study information

• Verified date: March 2018
• Source: Morphotek
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 130
• Est. completion date: November 1, 2013
• Est. primary completion date: December 15, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of Lung
• Adenocarcinoma of the Lung

Intervention

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:
• 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.

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].
• Paclitaxel
Paclitaxel 200 mg/m^2 will be administered intravenously.
• Pemetrexed
Pemetrexed 500 mg/m^2 will be administered intravenously.
• Cisplatin
Cisplatin 75 mg/m^2 will be administered intravenously.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital, Cancer Centre	Adelaide	South Australia
Australia	Flinders Medical Centre, Dept. of Oncology	Bedford Park	South Australia
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Royal Brisbane and Women's Hospital, Dept. of Medical Oncology	Brisbane	Queensland
Australia	Lyell McEwin Hospital	Elizabeth Vale	South Australia
Australia	Frankston Hospital, Oncology Day Unit	Frankston	Victoria
Australia	Fremantle Hospital	Fremantle	Western Australia
Australia	Epworth Healthcare	Richmond	Victoria
Australia	The Tweed Hospital	Tweed Heads	New South Wales
Australia	Southern Medical Day Oncology Care Centre	Wollongong	New South Wales
Australia	The Queen Elizabeth Hospital	Woodville South	South Australia
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Canada	Royal Victoria Hospital	Barrie	Ontario
Canada	Grand River Regional Cancer Centre	Kitchener	Ontario
Canada	Jewish General Hospital	Montréal	Quebec
Canada	Princess Margaret Hospital	Toronto	Ontario
Germany	HELIOS Klinikum Emil von Behring	Berlin
Germany	Krankenhaus Nordwest GmbH	Frankfurt am Main	Hessen
Germany	Asklepios Fachkliniken München-Gauting	Gauting	Bayern
Germany	Städtisches Krankenhaus Martha-Maria Halle Dölau gGmbH	Halle	Sachsen-anhalt
Germany	Asklepios Klinik Harburg	Hamburg
Germany	Universitätsklinikum Heidelberg	Heidelberg	Baden-wuerttemberg
Germany	Klinik Löwenstein gGmbH	Löwenstein	Baden-wuerttemberg
Germany	Johannes-Wesling-Klinikum Minden	Minden	Nordrhein-westfalen
Italy	Istituto Nazionale per la Ricerca sul Cancro	Genova
Italy	Ospedale Unico Versilia	Lido di Camaiore	Lucca
Italy	A.O. Seconda Università degli Studi di Napoli	Napoli
Italy	Azienda Ospedaliero-Univesitaria "San Luigi Gonzaga"	Orbassano	Torino
Poland	Specjalistyczny Szpital im. Alfreda Sokolowskiego	Szczecin	Zachodniopomorskie
Poland	Wojewódzki Szpital Zespolony im. L. Rydygiera w Toruniu Szpital Dzieciecy	Torun	Kujawsko-pomorskie
Poland	Centrum Onkologii - Instytut im. M. Sklodowskiej-Curie w Warszawie	Warszawa	Mazowieckie
Russian Federation	Republican Clinical Oncologic Dispensary of Ministry of health of Republic Tatarstan	Kazan	Tatarstan
Russian Federation	Cancer Research Center n.a. N.N. Blokhin	Moscow
Russian Federation	City Oncology Hospital # 62	Moscow
Spain	Hospital Clinic i Provincial de Barcelona	Barcelona
Spain	Hospital General Vall d'Hebron, Barcelona	Barcelona
Spain	Hospital Germans Trías i Pujol	Barcelona
Spain	Fundación Jiménez Díaz	Madrid
Spain	Hospital Regional Carlos Haya	Málaga	Malaga
United States	Christus Saint Frances, Cabrini Hospital, Cabrini Cancer Center	Alexandria	Louisiana
United States	Texas Oncology - Bedford	Bedford	Texas
United States	National Cancer Institute	Bethesda	Maryland
United States	St. Luke's Cancer Center Associates	Bethlehem	Pennsylvania
United States	Providence Health System	Beverly Hills	California
United States	Center for Hematology-Oncology	Boca Raton	Florida
United States	University Hematology Oncology, Inc.	Centralia	Illinois
United States	Ironwood Cancer and Research Center	Chandler	Arizona
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Maryland Oncology Hematology, P.A.	Columbia	Maryland
United States	Medical Specialists of the Palm Beaches	Deerfield Beach	Florida
United States	Rocky Mountain Cancer Centers, LLP	Denver	Colorado
United States	Englewood Hospital and Medical Center	Englewood	New Jersey
United States	Willamette Valley Cancer Institute and Research Center	Eugene	Oregon
United States	Deaconess Clinic Downtown	Evansville	Indiana
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	Detroit Clinical Research Center	Farmington Hills	Michigan
United States	Broward General Medical Center	Fort Lauderdale	Florida
United States	Cancer Care Associates of Fresno Medical Group, Inc.	Fresno	California
United States	University of Texas Medical Branch	Galveston	Texas
United States	Gettysburg Cancer Center	Gettysburg	Pennsylvania
United States	Medical Oncology Hematology	Gilroy	California
United States	Arizona Center for Hematology Oncology	Glendale	Arizona
United States	Cancer Team Bellin Health	Green Bay	Wisconsin
United States	California Cancer Care, Inc.	Greenbrae	California
United States	Kentucky Cancer Center	Hazard	Kentucky
United States	Houston Cancer Institute	Houston	Texas
United States	Queens Hospital Center	Jamaica	New York
United States	Moores University of California San Diego Cancer Center	La Jolla	California
United States	Wilshire Medical Oncology Group	La Verne	California
United States	Cancer Care of North Florida	Lake City	Florida
United States	Baptist Health System, Inc.	Lexington	Kentucky
United States	Glendale Adventist Medical Center	Los Angeles	California
United States	Hematology and Oncology Specialists, LLC	Metairie	Louisiana
United States	Clinical Trials and Research Associates, Inc.	Montebello	California
United States	The Community Hospital	Munster	Indiana
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Florida Cancer Institute-New Hope	New Port Richey	Florida
United States	Ocala Oncology Center, PL	Ocala	Florida
United States	North Country Oncology-Hematology	Oceanside	California
United States	MD Anderson Cancer Center-Orlando	Orlando	Florida
United States	Berkshire Hematology Oncology, PC	Pittsfield	Massachusetts
United States	Texas Oncology - Plano East	Plano	Texas
United States	Delta Hematology Oncology Associates, PC	Portsmouth	Virginia
United States	Pacific Hematology Oncology Associates	San Francisco	California
United States	Central Coast Medical Oncology	Santa Maria	California
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Medical Oncology Associates, PS	Spokane	Washington
United States	Rockwood Cancer Treatment Center	Spokane	Washington
United States	Hematology Oncology Associates, P.C.	Stamford	Connecticut
United States	Northwest Cancer Center	Sugar Land	Texas
United States	Syracuse Veterns Affairs Medical Center	Syracuse	New York
United States	Texas Oncology - Tyler	Tyler	Texas
United States	Texas Oncology - Waco	Waco	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Morphotek

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Germany,  Italy,  Poland,  Russian Federation,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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