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

This study has been completed.
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
BioVex Limited
ClinicalTrials.gov Identifier:
NCT00769704
First received: October 7, 2008
Last updated: June 14, 2016
Last verified: June 2016
  Purpose
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.

Condition Intervention Phase
Melanoma
Biological: Talimogene laherparepvec
Biological: GM-CSF
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by BioVex Limited:

Primary Outcome Measures:
  • Durable Response Rate [ Time Frame: From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months. ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Overall Survival [ Time Frame: 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. ] [ Designated as safety issue: No ]
    Overall survival was defined as the time from the date of randomization to the date of death from any cause. Overall survival time was censored at the last date the patient was known to be alive when the confirmation of death was absent or unknown. Participants were censored at the date of randomization if no additional follow-up data were obtained.

  • Objective Response Rate [ Time Frame: From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months. ] [ Designated as safety issue: No ]

    Objective response rate was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) assessed by the Endpoint Assessment Committee (EAC). Best overall response for a patient is the best overall response observed across all time points.

    Disease assessments were performed at the beginning of each treatment cycle and assessed 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.


  • Duration of Response [ Time Frame: From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months. ] [ Designated as safety issue: No ]
    The duration of response is defined as the longest individual period from entering response (CR or PR as assessed by the EAC) to the first documented evidence of the patient no longer meeting the criteria for being in response or death, whichever is earlier. Responses were censored at the last assessment showing response.

  • Response Onset [ Time Frame: From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months. ] [ Designated as safety issue: No ]
    Response onset is defined as the time from the date of randomization to the date of the first documented evidence of response (CR or PR) per EAC assessment.

  • Time to Treatment Failure [ Time Frame: From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months. ] [ Designated as safety issue: No ]

    Time to treatment failure was assessed by the investigator, and calculated from randomization until the first clinically relevant disease progression where there is no response achieved after the progression, or until death if no such progression occurs. Participants who did not have clinically relevant progression or did not die were censored at the time of the their last tumor assessment. Participants who withdrew from treatment due to a clinically unacceptable toxicity were not considered as an event in the analysis.

    Progressive disease (PD) is defined as a ≥ 25% increase in the sum of the products of the perpendicular diameters of all measurable tumors since baseline, or the unequivocal appearance of a new tumor since the last response assessment time point.

    Clinically relevant progressive disease is PD that is associated with a decline in performance status and/or in the opinion of the investigator the patient requires alternative therapy.


  • Response Interval [ Time Frame: From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months. ] [ Designated as safety issue: No ]
    Response interval is defined as the interval between the date of randomization and the date of the last documented evidence of response (CR or PR as assessed by the Investigator) prior to any new anti-cancer therapy. Response Interval post response onset was censored if a patient was still in response at the last observation.


Enrollment: 437
Study Start Date: April 2009
Study Completion Date: September 2014
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.
Biological: GM-CSF
125 µg/m² subcutaneous injection
Other Names:
  • Leukine
  • Sargramostim
Experimental: 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.
Biological: Talimogene laherparepvec
Up to 4 mL of 10⁸ pfu/mL/per intratumoral injection
Other Names:
  • OncoVEX^GM-CSF
  • IMLYGIC™

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00769704

  Hide Study Locations
Locations
United States, Arizona
University of Arizona Cancer Center
Tucson, Arizona, United States, 85724
United States, Arkansas
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, California
University of California San Diego, Moores Cancer Center
La Jolla, California, United States, 92093
UCLA Medical Center
Los Angeles, California, United States, 90095
San Francisco Oncology Associates
San Francisco, California, United States, 94115
Northern California Melanoma Center, St. Mary's Medical Center
San Francisco, California, United States, 94117
John Wayne Cancer Institute
Santa Monica, California, United States, 90404
Redwood Regional Medical Group Inc, North Bay Melanoma Program
Sebastopol, California, United States, 95472
United States, Colorado
University of Colorado Cancer Center
Aurora, Colorado, United States, 80014
United States, Florida
Baptist Cancer Institute
Jacksonville, Florida, United States, 32207
Lakeland Regional Cancer Center
Lakeland, Florida, United States, 33805
Mount Sinai Medical Center CCOP
Miami Beach, Florida, United States, 33140
University of Miami
Miami, Florida, United States, 33136
MD Anderson Cancer Center Orlando
Orlando, Florida, United States, 32806
H. Lee Moffitt Cancer Center
Tampa, Florida, United States, 33612
Palm Beach Cancer Institute
West Palm Beach, Florida, United States, 33401
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
Cancer Care Center at Lutheran General Hospital
Park Ridge, Illinois, United States, 60068
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
Investigative Clinical Research of Indiana
Indianapolis, Indiana, United States, 46254
United States, Iowa
University of Iowa Hospitals & Clinics
Iowa City, Iowa, United States, 52242
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66205
United States, Kentucky
James Graham Brown Cancer Center
Louisville, Kentucky, United States, 40202
United States, Massachusetts
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States, 02114
United States, Minnesota
Hubert H Humphrey Cancer Center
Robbinsdale, Minnesota, United States, 55422
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
Kansas City Cancer Center
Kansas City, Missouri, United States, 66210
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
St. Louis University Hospital
St. Louis, Missouri, United States, 63110
United States, Nebraska
Methodist Estabrook Cancer Center
Omaha, Nebraska, United States, 68114
United States, New Jersey
Mountainside Hospital
Morristown, New Jersey, United States, 07962
United States, New Mexico
New Mexico Cancer Care Alliance
Albuquerque, New Mexico, United States, 87109
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Columbia Medical University
New York, New York, United States, 10032
Mount Sinai School of Medicine
New York, New York, United States, 10032
United States, North Carolina
University of North Carolina At Chapel Hill School of Medicine
Chapel Hill, North Carolina, United States, 27599
Duke University Medical Center
Durham, North Carolina, United States, 27710
Wake Forest University School of Medicine
Winston Salem, North Carolina, United States, 27157
United States, Ohio
Gabrail Cancer Center
Canton, Ohio, United States, 44718
Barrett Cancer Center
Cincinnati, Ohio, United States, 45267
Cleveland Clinic Foundation, Taussig Cancer Center
Cleveland, Ohio, United States, 44195
United States, Oregon
Earle A Chiles Research Institute, Providence Cancer Center
Portland, Oregon, United States, 97213
United States, Pennsylvania
St Luke's Hospital & Health Network
Bethlehem, Pennsylvania, United States, 18015
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
United States, Rhode Island
Rhode Island Hospital
Providence, Rhode Island, United States, 02905
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Institute for Translational Oncology Research
Greenville, South Carolina, United States, 29605
United States, Tennessee
Vanderbilt Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Texas
Texas Cancer Center, Abilene
Abilene, Texas, United States, 79701
Mary Crowley Medical Research Center
Dallas, Texas, United States, 75246
University of Texas - MD Anderson
Houston, Texas, United States, 77030
Texas Oncology, Allison Cancer Center
Midland, Texas, United States, 79701
United States, Utah
Intermountain Medical Center
Murray, Utah, United States, 84107
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
United States, Virginia
Oncology and Hematology Associates of Southwest Virginia, Inc.
Salem, Virginia, United States, 24153
United States, Wisconsin
Aurora/St. Luke's Medical Center
Milwaukee, Wisconsin, United States, 53215
Canada, Alberta
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G2M9
Canada, Quebec
Jewish General Hospital
Montreal, Quebec, Canada, H3T 1E2
South Africa
GVI Oncology
Port Elizabeth, Eastern Cape, South Africa, 6045
Dr. Fourie & Bonnet
Bloemfontein, Free State, South Africa, 9301
Medical Oncology Centre of Rosebank
Johannesburg, Gauteng, South Africa, 2196
Wits Donald Gordon Clinical Trial Site
Parktown, Guateng, South Africa, 2193
University of Pretoria
Pretoria, Guateng, South Africa, 0001
Mary Potter Oncology Centre
Pretoria, Guateng, South Africa, 0075
Hopelands Cancer Centre
Pietermaritzburg, Kwa-Zulu Natal, South Africa, 3201
Wilgers Oncology Center
Hatfield, Pretoria, South Africa, 0028
GVI Onocology Clinical Trials Unit
Cape Town, Western Cape, South Africa, 7500
GVI Oncology Centre
Cape Town, Western Cape, South Africa
United Kingdom
University of Birmingham
Birmingham, United Kingdom, B15 2TT
Addenbrookes Hospital
Cambridge, United Kingdom, CB2 0QQ
Broomfield Hospital
Chelmsford, United Kingdom, CM1 7ET
St. James's University Hospital
Leeds, United Kingdom, LS9 7TF
Leicester Royal Infirmary
Leicester, United Kingdom, LE1 5WW
Royal Free Hospital
London, United Kingdom, NW3 2QG
St. George's University of London
London, United Kingdom, SW17 0RE
Royal Marsden Hospital
London, United Kingdom, SW3 6JJ
Freeman Hospital
Newcastle upon Tyne, United Kingdom, NE7 7DN
Nottingham City Hospital
Nottingham, United Kingdom, NG5 1PB
Churchill Hospital
Oxford, United Kingdom, OX3 7LJ
Southampton General Hospital
Southampton, United Kingdom, SO16 6YD
Clatterbridge Centre for Oncology
Wirral, United Kingdom, CH63 4JY
Sponsors and Collaborators
BioVex Limited
Amgen
Investigators
Study Director: MD Amgen
  More Information

Publications:
Responsible Party: BioVex Limited
ClinicalTrials.gov Identifier: NCT00769704     History of Changes
Other Study ID Numbers: 005/05  20110263  2008-006140-20 
Study First Received: October 7, 2008
Results First Received: September 22, 2015
Last Updated: June 14, 2016
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Canada: Health Canada
South Africa: Medicines Control Council

Keywords provided by BioVex Limited:
Melanoma
OncoVEX^GM-CSF
GM-CSF
Stage IIIb, IIIc and IV Disease
oncolytic
OncoVex
T-Vec
talimogene laherparepvec

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on August 25, 2016