Clinical trial NCT00769704: Efficacy and Safety Study of Talimogene Laherparepvec Compared to Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) in Melanoma
Official title: A Randomized Phase 3 Clinical Trial to Evaluate the Efficacy and Safety of Treatment With OncoVEX^GM-CSF Compared to Subcutaneously Administered GM-CSF in Melanoma Patients With Unresectable Stage IIIb, IIIc and IV Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Melanoma
Keywords: Melanoma
OncoVEX^GM-CSF
GM-CSF
Stage IIIb, IIIc and IV Disease
oncolytic
OncoVex
T-Vec
talimogene laherparepvec
Lead sponsor: BioVex Limited
Sponsor class: INDUSTRY
Collaborators: name: Amgen
First posted: 2008-10-09
Enrollment: 437
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to evaluate the efficacy and safety of treatment with talimogene laherparepvec compared to subcutaneously administered GM-CSF in patients with unresectable Stage IIIb, IIIc and Stage IV melanoma. The efficacy endpoints of the study aim to demonstrate overall clinical benefit for patients treated with talimogene laherparepvec as compared to GM-CSF.


Eligibility criteria: Inclusion Criteria:

* Males or females age ≥ 18 years
* Stage IIIb, IIIc or stage IV disease that is not surgically resectable
* Injectable disease (i.e. suitable for direct injection or through the use of ultrasound guidance)
* At least 1 injectable cutaneous, subcutaneous or nodal melanoma lesion \>= 10 mm in longest diameter or, multiple injectable melanoma lesions which in aggregate have a longest diameter of \>= 10 mm
* Serum lactate dehydrogenase (LDH) levels less than 1.5 x upper limit of normal (ULN)
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Prolongation in International Normalized Ratio (INR), Prothrombin Time (PT), and Partial Thromboplastin Time (PTT) when the result is from therapeutic anticoagulation treatment are permitted for patients whose injectable lesions are cutaneous and/or subcutaneous such that direct pressure could be applied in the event of excessive bleeding

Exclusion Criteria:

* Clinically active cerebral or any bone metastases. Patients with up to 3 (neurological performance status of 0) cerebral metastases may be enrolled, provided that all lesions have been adequately treated with stereotactic radiation therapy, craniotomy, gammaknife therapy, with no evidence of progression, and have not required steroids, for at least two (2) months prior to randomization
* Greater than 3 visceral metastases (this does not include lung metastases or nodal metastases associated with visceral organs). For patients with \< 3 visceral metastases, no lesion \> 3 cm, and liver lesions must meet Response Evaluation Criteria In Solid Tumors (RECIST) criteria for stable disease for at least 1 month prior to randomization

Primary outcomes:
measure: Durable Response Rate
timeFrame: From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months.
Secondary outcomes:
measure: Overall Survival
timeFrame: From randomization until the first 290 survival events had occurred (data cut-off date of 31 March 2014); median time on follow-up was 44 months.
measure: Objective Response Rate
timeFrame: From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months.
measure: Duration of Response
timeFrame: From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months.
measure: Response Onset
timeFrame: From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months.
measure: Time to Treatment Failure
timeFrame: From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months.
measure: Response Interval
timeFrame: From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months.
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona Cancer Center
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: La Jolla
country: United States
facility: University of California San Diego, Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: San Francisco
country: United States
facility: San Francisco Oncology Associates
state: California
city: San Francisco
country: United States
facility: Northern California Melanoma Center, St. Mary's Medical Center
state: California
city: Santa Monica
country: United States
facility: John Wayne Cancer Institute
state: California
city: Sebastopol
country: United States
facility: Redwood Regional Medical Group Inc, North Bay Melanoma Program
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Jacksonville
country: United States
facility: Baptist Cancer Institute
state: Florida
city: Lakeland
country: United States
facility: Lakeland Regional Cancer Center
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center CCOP
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Orlando
country: United States
facility: MD Anderson Cancer Center Orlando
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Cancer Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Park Ridge
country: United States
facility: Cancer Care Center at Lutheran General Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Indianapolis
country: United States
facility: Investigative Clinical Research of Indiana
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Louisville
country: United States
facility: James Graham Brown Cancer Center
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Robbinsdale
country: United States
facility: Hubert H Humphrey Cancer Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Kansas City
country: United States
facility: Kansas City Cancer Center
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: St. Louis
country: United States
facility: St. Louis University Hospital
state: Missouri
city: Omaha
country: United States
facility: Methodist Estabrook Cancer Center
state: Nebraska
city: Morristown
country: United States
facility: Mountainside Hospital
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico Cancer Care Alliance
state: New Mexico
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Columbia Medical University
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina At Chapel Hill School of Medicine
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston Salem
country: United States
facility: Wake Forest University School of Medicine
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Cincinnati
country: United States
facility: Barrett Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation, Taussig Cancer Center
state: Ohio
city: Portland
country: United States
facility: Earle A Chiles Research Institute, Providence Cancer Center
state: Oregon
city: Bethlehem
country: United States
facility: St Luke's Hospital & Health Network
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Greenville
country: United States
facility: Institute for Translational Oncology Research
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt Ingram Cancer Center
state: Tennessee
city: Abilene
country: United States
facility: Texas Cancer Center, Abilene
state: Texas
city: Dallas
country: United States
facility: Mary Crowley Medical Research Center
state: Texas
city: Houston
country: United States
facility: University of Texas - MD Anderson
state: Texas
city: Midland
country: United States
facility: Texas Oncology, Allison Cancer Center
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Salem
country: United States
facility: Oncology and Hematology Associates of Southwest Virginia, Inc.
state: Virginia
city: Milwaukee
country: United States
facility: Aurora/St. Luke's Medical Center
state: Wisconsin
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Port Elizabeth
country: South Africa
facility: GVI Oncology
state: Eastern Cape
city: Bloemfontein
country: South Africa
facility: Dr. Fourie & Bonnet
state: Free State
city: Johannesburg
country: South Africa
facility: Medical Oncology Centre of Rosebank
state: Gauteng
city: Parktown
country: South Africa
facility: Wits Donald Gordon Clinical Trial Site
state: Guateng
city: Pretoria
country: South Africa
facility: University of Pretoria
state: Guateng
city: Pretoria
country: South Africa
facility: Mary Potter Oncology Centre
state: Guateng
city: Pietermaritzburg
country: South Africa
facility: Hopelands Cancer Centre
state: Kwa-Zulu Natal
city: Hatfield
country: South Africa
facility: Wilgers Oncology Center
state: Pretoria
city: Cape Town
country: South Africa
facility: GVI Onocology Clinical Trials Unit
state: Western Cape
city: Cape Town
country: South Africa
facility: GVI Oncology Centre
state: Western Cape
city: Birmingham
country: United Kingdom
facility: University of Birmingham
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital
city: Chelmsford
country: United Kingdom
facility: Broomfield Hospital
city: Leeds
country: United Kingdom
facility: St. James's University Hospital
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: St. George's University of London
city: London
country: United Kingdom
facility: Royal Marsden Hospital
city: Newcastle upon Tyne
country: United Kingdom
facility: Freeman Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
city: Oxford
country: United Kingdom
facility: Churchill Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
city: Wirral
country: United Kingdom
facility: Clatterbridge Centre for Oncology
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Andtbacka RH, Kaufman HL, Collichio F, Amatruda T, Senzer N, Chesney J, Delman KA, Spitler LE, Puzanov I, Agarwala SS, Milhem M, Cranmer L, Curti B, Lewis K, Ross M, Guthrie T, Linette GP, Daniels GA, Harrington K, Middleton MR, Miller WH Jr, Zager JS, Ye Y, Yao B, Li A, Doleman S, VanderWalde A, Gansert J, Coffin RS. Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma. J Clin Oncol. 2015 Sep 1;33(25):2780-8. doi: 10.1200/JCO.2014.58.3377. Epub 2015 May 26.
citation: Andtbacka RHI, Collichio F, Harrington KJ, Middleton MR, Downey G, Ӧhrling K, Kaufman HL. Final analyses of OPTiM: a randomized phase III trial of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in unresectable stage III-IV melanoma. J Immunother Cancer. 2019 Jun 6;7(1):145. doi: 10.1186/s40425-019-0623-z.
citation: Kaufman HL, Andtbacka RHI, Collichio FA, Wolf M, Zhao Z, Shilkrut M, Puzanov I, Ross M. Durable response rate as an endpoint in cancer immunotherapy: insights from oncolytic virus clinical trials. J Immunother Cancer. 2017 Sep 19;5(1):72. doi: 10.1186/s40425-017-0276-8.