Efficacy and Safety Study of Talimogene Laherparepvec Compared to Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) in Melanoma

NCT ID: NCT00769704

Last Updated: 2016-07-13

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

437 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-04-30

Study Completion Date

2014-09-30

Brief Summary

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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.

Detailed Description

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Conditions

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Melanoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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GM-CSF

Granulocyte 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.

Group Type ACTIVE_COMPARATOR

GM-CSF

Intervention Type BIOLOGICAL

125 µg/m² subcutaneous injection

Talimogene Laherparepvec

Participants 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.

Group Type EXPERIMENTAL

Talimogene laherparepvec

Intervention Type BIOLOGICAL

Up to 4 mL of 10⁸ pfu/mL/per intratumoral injection

Interventions

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Talimogene laherparepvec

Up to 4 mL of 10⁸ pfu/mL/per intratumoral injection

Intervention Type BIOLOGICAL

GM-CSF

125 µg/m² subcutaneous injection

Intervention Type BIOLOGICAL

Other Intervention Names

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OncoVEX^GM-CSF IMLYGIC™ Leukine Sargramostim

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role collaborator

BioVex Limited

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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MD

Role: STUDY_DIRECTOR

Amgen

Locations

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University of Arizona Cancer Center

Tucson, Arizona, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

University of California San Diego, Moores Cancer Center

La Jolla, California, United States

Site Status

UCLA Medical Center

Los Angeles, California, United States

Site Status

San Francisco Oncology Associates

San Francisco, California, United States

Site Status

Northern California Melanoma Center, St. Mary's Medical Center

San Francisco, California, United States

Site Status

John Wayne Cancer Institute

Santa Monica, California, United States

Site Status

Redwood Regional Medical Group Inc, North Bay Melanoma Program

Sebastopol, California, United States

Site Status

University of Colorado Cancer Center

Aurora, Colorado, United States

Site Status

Baptist Cancer Institute

Jacksonville, Florida, United States

Site Status

Lakeland Regional Cancer Center

Lakeland, Florida, United States

Site Status

University of Miami

Miami, Florida, United States

Site Status

Mount Sinai Medical Center CCOP

Miami Beach, Florida, United States

Site Status

MD Anderson Cancer Center Orlando

Orlando, Florida, United States

Site Status

H. Lee Moffitt Cancer Center

Tampa, Florida, United States

Site Status

Palm Beach Cancer Institute

West Palm Beach, Florida, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

Cancer Care Center at Lutheran General Hospital

Park Ridge, Illinois, United States

Site Status

Indiana University

Indianapolis, Indiana, United States

Site Status

Investigative Clinical Research of Indiana

Indianapolis, Indiana, United States

Site Status

University of Iowa Hospitals & Clinics

Iowa City, Iowa, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

James Graham Brown Cancer Center

Louisville, Kentucky, United States

Site Status

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Site Status

Hubert H Humphrey Cancer Center

Robbinsdale, Minnesota, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Kansas City Cancer Center

Kansas City, Missouri, United States

Site Status

St. Louis University Hospital

St Louis, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Methodist Estabrook Cancer Center

Omaha, Nebraska, United States

Site Status

Mountainside Hospital

Morristown, New Jersey, United States

Site Status

New Mexico Cancer Care Alliance

Albuquerque, New Mexico, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Columbia Medical University

New York, New York, United States

Site Status

Mount Sinai School of Medicine

New York, New York, United States

Site Status

University of North Carolina At Chapel Hill School of Medicine

Chapel Hill, North Carolina, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Wake Forest University School of Medicine

Winston-Salem, North Carolina, United States

Site Status

Gabrail Cancer Center

Canton, Ohio, United States

Site Status

Barrett Cancer Center

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic Foundation, Taussig Cancer Center

Cleveland, Ohio, United States

Site Status

Earle A Chiles Research Institute, Providence Cancer Center

Portland, Oregon, United States

Site Status

St Luke's Hospital & Health Network

Bethlehem, Pennsylvania, United States

Site Status

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Institute for Translational Oncology Research

Greenville, South Carolina, United States

Site Status

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Texas Cancer Center, Abilene

Abilene, Texas, United States

Site Status

Mary Crowley Medical Research Center

Dallas, Texas, United States

Site Status

University of Texas - MD Anderson

Houston, Texas, United States

Site Status

Texas Oncology, Allison Cancer Center

Midland, Texas, United States

Site Status

Intermountain Medical Center

Murray, Utah, United States

Site Status

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

Oncology and Hematology Associates of Southwest Virginia, Inc.

Salem, Virginia, United States

Site Status

Aurora/St. Luke's Medical Center

Milwaukee, Wisconsin, United States

Site Status

Cross Cancer Institute

Edmonton, Alberta, Canada

Site Status

Princess Margaret Hospital

Toronto, Ontario, Canada

Site Status

Jewish General Hospital

Montreal, Quebec, Canada

Site Status

GVI Oncology

Port Elizabeth, Eastern Cape, South Africa

Site Status

Dr. Fourie & Bonnet

Bloemfontein, Free State, South Africa

Site Status

Medical Oncology Centre of Rosebank

Johannesburg, Gauteng, South Africa

Site Status

Wits Donald Gordon Clinical Trial Site

Parktown, Guateng, South Africa

Site Status

University of Pretoria

Pretoria, Guateng, South Africa

Site Status

Mary Potter Oncology Centre

Pretoria, Guateng, South Africa

Site Status

Hopelands Cancer Centre

Pietermaritzburg, KwaZulu-Natal, South Africa

Site Status

Wilgers Oncology Center

Hatfield, Pretoria, South Africa

Site Status

GVI Onocology Clinical Trials Unit

Cape Town, Western Cape, South Africa

Site Status

GVI Oncology Centre

Cape Town, Western Cape, South Africa

Site Status

University of Birmingham

Birmingham, , United Kingdom

Site Status

Addenbrookes Hospital

Cambridge, , United Kingdom

Site Status

Broomfield Hospital

Chelmsford, , United Kingdom

Site Status

St. James's University Hospital

Leeds, , United Kingdom

Site Status

Leicester Royal Infirmary

Leicester, , United Kingdom

Site Status

Royal Free Hospital

London, , United Kingdom

Site Status

St. George's University of London

London, , United Kingdom

Site Status

Royal Marsden Hospital

London, , United Kingdom

Site Status

Clatterbridge Centre for Oncology

Metropolitan Borough of Wirral, , United Kingdom

Site Status

Freeman Hospital

Newcastle upon Tyne, , United Kingdom

Site Status

Nottingham City Hospital

Nottingham, , United Kingdom

Site Status

Churchill Hospital

Oxford, , United Kingdom

Site Status

Southampton General Hospital

Southampton, , United Kingdom

Site Status

Countries

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United States Canada South Africa United Kingdom

References

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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.

Reference Type RESULT
PMID: 26014293 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31171039 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28923101 (View on PubMed)

Other Identifiers

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20110263

Identifier Type: OTHER

Identifier Source: secondary_id

2008-006140-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

005/05

Identifier Type: -

Identifier Source: org_study_id

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