Efficacy and Safety Study of Talimogene Laherparepvec Compared to Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) in Melanoma
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
3 other identifiers
interventional
437
4 countries
83
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Apr 2009
Longer than P75 for phase_3
83 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 7, 2008
CompletedFirst Posted
Study publicly available on registry
October 9, 2008
CompletedStudy Start
First participant enrolled
April 1, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2014
CompletedResults Posted
Study results publicly available
December 17, 2015
CompletedJuly 13, 2016
June 1, 2016
3.8 years
October 7, 2008
September 22, 2015
June 14, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Durable Response Rate
Durable response rate was defined as the percentage of participants with a complete response (CR) or partial response (PR) maintained continuously for at least 6 months from the time the objective response was first observed and initiating within 12 months of starting therapy as assessed by the Endpoint Assessment Committee (EAC). This reflects all new sites of disease as well as disease sites identified at baseline. Disease assessments were performed at the beginning of each treatment cycle in accordance with modified World Health Organization criteria. CR: Disappearance of all clinical evidence of tumor (both measurable and non-measurable but evaluable disease); PR: ≥ 50% reduction in the sum of the products of the perpendicular diameters of all measurable tumors at the time of assessment as compared to baseline.
From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months.
Secondary Outcomes (6)
Overall Survival
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.
Objective Response Rate
From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months.
Duration of Response
From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months.
Response Onset
From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months.
Time to Treatment Failure
From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months.
- +1 more secondary outcomes
Study Arms (2)
GM-CSF
ACTIVE COMPARATORGranulocyte macrophage colony-stimulating factor (GM-CSF) was administered at a dose of 125 μg/m²/day subcutaneously for 14 days, followed by a 14-day rest period for 24 weeks. Participants could continue treatment until clinically relevant disease progression, intolerability, withdrawal of consent, complete remission, or lack of response by 12 months, for a maximum of 18 months.
Talimogene Laherparepvec
EXPERIMENTALParticipants received talimogene laherparepvec on Days 1 and 15 of each 28-day cycle for 24 weeks. The initial dose of talimogene laherparepvec was at a concentration of 10⁶ plaque forming units (PFU)/mL, injected into 1 or more skin, subcutaneous or nodal tumors. Subsequent doses began at least 3 weeks after the first dose and consisted of talimogene laherparepvec at a concentration of 10⁸ PFU/mL. Participants could continue treatment until clinically relevant disease progression, intolerability, withdrawal of consent, complete remission, lack of response by 12 months, or disappearance of all injectable lesions, for a maximum of 18 months.
Interventions
Up to 4 mL of 10⁸ pfu/mL/per intratumoral injection
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- BioVex Limitedlead
- Amgencollaborator
Study Sites (83)
University of Arizona Cancer Center
Tucson, Arizona, 85724, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205, United States
University of California San Diego, Moores Cancer Center
La Jolla, California, 92093, United States
UCLA Medical Center
Los Angeles, California, 90095, United States
San Francisco Oncology Associates
San Francisco, California, 94115, United States
Northern California Melanoma Center, St. Mary's Medical Center
San Francisco, California, 94117, United States
John Wayne Cancer Institute
Santa Monica, California, 90404, United States
Redwood Regional Medical Group Inc, North Bay Melanoma Program
Sebastopol, California, 95472, United States
University of Colorado Cancer Center
Aurora, Colorado, 80014, United States
Baptist Cancer Institute
Jacksonville, Florida, 32207, United States
Lakeland Regional Cancer Center
Lakeland, Florida, 33805, United States
University of Miami
Miami, Florida, 33136, United States
Mount Sinai Medical Center CCOP
Miami Beach, Florida, 33140, United States
MD Anderson Cancer Center Orlando
Orlando, Florida, 32806, United States
H. Lee Moffitt Cancer Center
Tampa, Florida, 33612, United States
Palm Beach Cancer Institute
West Palm Beach, Florida, 33401, United States
Emory University
Atlanta, Georgia, 30322, United States
Rush University Medical Center
Chicago, Illinois, 60612, United States
Cancer Care Center at Lutheran General Hospital
Park Ridge, Illinois, 60068, United States
Indiana University
Indianapolis, Indiana, 46202, United States
Investigative Clinical Research of Indiana
Indianapolis, Indiana, 46254, United States
University of Iowa Hospitals & Clinics
Iowa City, Iowa, 52242, United States
University of Kansas Medical Center
Kansas City, Kansas, 66205, United States
James Graham Brown Cancer Center
Louisville, Kentucky, 40202, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114, United States
Hubert H Humphrey Cancer Center
Robbinsdale, Minnesota, 55422, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Kansas City Cancer Center
Kansas City, Missouri, 66210, United States
St. Louis University Hospital
St Louis, Missouri, 63110, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Methodist Estabrook Cancer Center
Omaha, Nebraska, 68114, United States
Mountainside Hospital
Morristown, New Jersey, 07962, United States
New Mexico Cancer Care Alliance
Albuquerque, New Mexico, 87109, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Columbia Medical University
New York, New York, 10032, United States
Mount Sinai School of Medicine
New York, New York, 10032, United States
University of North Carolina At Chapel Hill School of Medicine
Chapel Hill, North Carolina, 27599, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Wake Forest University School of Medicine
Winston-Salem, North Carolina, 27157, United States
Gabrail Cancer Center
Canton, Ohio, 44718, United States
Barrett Cancer Center
Cincinnati, Ohio, 45267, United States
Cleveland Clinic Foundation, Taussig Cancer Center
Cleveland, Ohio, 44195, United States
Earle A Chiles Research Institute, Providence Cancer Center
Portland, Oregon, 97213, United States
St Luke's Hospital & Health Network
Bethlehem, Pennsylvania, 18015, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107, United States
Rhode Island Hospital
Providence, Rhode Island, 02905, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Institute for Translational Oncology Research
Greenville, South Carolina, 29605, United States
Vanderbilt Ingram Cancer Center
Nashville, Tennessee, 37232, United States
Texas Cancer Center, Abilene
Abilene, Texas, 79701, United States
Mary Crowley Medical Research Center
Dallas, Texas, 75246, United States
University of Texas - MD Anderson
Houston, Texas, 77030, United States
Texas Oncology, Allison Cancer Center
Midland, Texas, 79701, United States
Intermountain Medical Center
Murray, Utah, 84107, United States
Huntsman Cancer Institute
Salt Lake City, Utah, 84112, United States
Oncology and Hematology Associates of Southwest Virginia, Inc.
Salem, Virginia, 24153, United States
Aurora/St. Luke's Medical Center
Milwaukee, Wisconsin, 53215, United States
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2, Canada
Princess Margaret Hospital
Toronto, Ontario, M5G2M9, Canada
Jewish General Hospital
Montreal, Quebec, H3T 1E2, Canada
GVI Oncology
Port Elizabeth, Eastern Cape, 6045, South Africa
Dr. Fourie & Bonnet
Bloemfontein, Free State, 9301, South Africa
Medical Oncology Centre of Rosebank
Johannesburg, Gauteng, 2196, South Africa
Wits Donald Gordon Clinical Trial Site
Parktown, Guateng, 2193, South Africa
University of Pretoria
Pretoria, Guateng, 0001, South Africa
Mary Potter Oncology Centre
Pretoria, Guateng, 0075, South Africa
Hopelands Cancer Centre
Pietermaritzburg, KwaZulu-Natal, 3201, South Africa
Wilgers Oncology Center
Hatfield, Pretoria, 0028, South Africa
GVI Onocology Clinical Trials Unit
Cape Town, Western Cape, 7500, South Africa
GVI Oncology Centre
Cape Town, Western Cape, South Africa
University of Birmingham
Birmingham, B15 2TT, United Kingdom
Addenbrookes Hospital
Cambridge, CB2 0QQ, United Kingdom
Broomfield Hospital
Chelmsford, CM1 7ET, United Kingdom
St. James's University Hospital
Leeds, LS9 7TF, United Kingdom
Leicester Royal Infirmary
Leicester, LE1 5WW, United Kingdom
Royal Free Hospital
London, NW3 2QG, United Kingdom
St. George's University of London
London, SW17 0RE, United Kingdom
Royal Marsden Hospital
London, SW3 6JJ, United Kingdom
Clatterbridge Centre for Oncology
Metropolitan Borough of Wirral, CH63 4JY, United Kingdom
Freeman Hospital
Newcastle upon Tyne, NE7 7DN, United Kingdom
Nottingham City Hospital
Nottingham, NG5 1PB, United Kingdom
Churchill Hospital
Oxford, OX3 7LJ, United Kingdom
Southampton General Hospital
Southampton, SO16 6YD, United Kingdom
Related Publications (3)
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.
PMID: 26014293RESULTAndtbacka 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.
PMID: 31171039DERIVEDKaufman 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.
PMID: 28923101DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Amgen, Inc.
Study Officials
- STUDY DIRECTOR
MD
Amgen
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 7, 2008
First Posted
October 9, 2008
Study Start
April 1, 2009
Primary Completion
February 1, 2013
Study Completion
September 1, 2014
Last Updated
July 13, 2016
Results First Posted
December 17, 2015
Record last verified: 2016-06