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

Melanoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00769704
• Other study ID #: 005/05
• Secondary ID: 201102632008-006
• Status: Completed
• Phase: Phase 3
• First received: October 7, 2008
• Last updated: November 12, 2015
• Start date: April 2009
• Est. completion date: September 2014

Study information

• Verified date: November 2015
• Source: BioVex Limited
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyCanada: Health CanadaSouth Africa: Medicines Control Council
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 437
• Est. completion date: September 2014
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Melanoma

Intervention

Biological:
• Talimogene laherparepvec
Up to 4 mL of 108 pfu/mL/per intratumoral injection
• GM-CSF
125 µg/m² subcutaneous injection

Locations

Country	Name	City	State
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Jewish General Hospital	Montreal	Quebec
Canada	Princess Margaret Hospital	Toronto	Ontario
South Africa	Dr. Fourie & Bonnet	Bloemfontein	Free State
South Africa	GVI Oncology Centre	Cape Town	Western Cape
South Africa	GVI Onocology Clinical Trials Unit	Cape Town	Western Cape
South Africa	Wilgers Oncology Center	Hatfield	Pretoria
South Africa	Medical Oncology Centre of Rosebank	Johannesburg	Gauteng
South Africa	Wits Donald Gordon Clinical Trial Site	Parktown	Guateng
South Africa	Hopelands Cancer Centre	Pietermaritzburg	Kwa-Zulu Natal
South Africa	GVI Oncology	Port Elizabeth	Eastern Cape
South Africa	Mary Potter Oncology Centre	Pretoria	Guateng
South Africa	University of Pretoria	Pretoria	Guateng
United Kingdom	University of Birmingham	Birmingham
United Kingdom	Addenbrookes Hospital	Cambridge
United Kingdom	Broomfield Hospital	Chelmsford
United Kingdom	St. James's University Hospital	Leeds
United Kingdom	Leicester Royal Infirmary	Leicester
United Kingdom	Royal Free Hospital	London
United Kingdom	Royal Marsden Hospital	London
United Kingdom	St. George's University of London	London
United Kingdom	Freeman Hospital	Newcastle upon Tyne
United Kingdom	Nottingham City Hospital	Nottingham
United Kingdom	Churchill Hospital	Oxford
United Kingdom	Southampton General Hospital	Southampton
United Kingdom	Clatterbridge Centre for Oncology	Wirral
United States	Texas Cancer Center, Abilene	Abilene	Texas
United States	New Mexico Cancer Care Alliance	Albuquerque	New Mexico
United States	Emory University	Atlanta	Georgia
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	St Luke's Hospital & Health Network	Bethlehem	Pennsylvania
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Gabrail Cancer Center	Canton	Ohio
United States	University of North Carolina At Chapel Hill School of Medicine	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Rush University Medical Center	Chicago	Illinois
United States	Barrett Cancer Center	Cincinnati	Ohio
United States	Cleveland Clinic Foundation, Taussig Cancer Center	Cleveland	Ohio
United States	Mary Crowley Medical Research Center	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	Institute for Translational Oncology Research	Greenville	South Carolina
United States	University of Texas - MD Anderson	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	Investigative Clinical Research of Indiana	Indianapolis	Indiana
United States	University of Iowa Hospitals & Clinics	Iowa City	Iowa
United States	Baptist Cancer Institute	Jacksonville	Florida
United States	Kansas City Cancer Center	Kansas City	Missouri
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of California San Diego, Moores Cancer Center	La Jolla	California
United States	Lakeland Regional Cancer Center	Lakeland	Florida
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	UCLA Medical Center	Los Angeles	California
United States	James Graham Brown Cancer Center	Louisville	Kentucky
United States	University of Miami	Miami	Florida
United States	Mount Sinai Medical Center CCOP	Miami Beach	Florida
United States	Texas Oncology, Allison Cancer Center	Midland	Texas
United States	Aurora/St. Luke's Medical Center	Milwaukee	Wisconsin
United States	Mountainside Hospital	Morristown	New Jersey
United States	Intermountain Medical Center	Murray	Utah
United States	Vanderbilt Ingram Cancer Center	Nashville	Tennessee
United States	Columbia Medical University	New York	New York
United States	Mount Sinai School of Medicine	New York	New York
United States	Methodist Estabrook Cancer Center	Omaha	Nebraska
United States	MD Anderson Cancer Center Orlando	Orlando	Florida
United States	Cancer Care Center at Lutheran General Hospital	Park Ridge	Illinois
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Earle A Chiles Research Institute, Providence Cancer Center	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Hubert H Humphrey Cancer Center	Robbinsdale	Minnesota
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Oncology and Hematology Associates of Southwest Virginia, Inc.	Salem	Virginia
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	Northern California Melanoma Center, St. Mary's Medical Center	San Francisco	California
United States	San Francisco Oncology Associates	San Francisco	California
United States	John Wayne Cancer Institute	Santa Monica	California
United States	Redwood Regional Medical Group Inc, North Bay Melanoma Program	Sebastopol	California
United States	St. Louis University Hospital	St. Louis	Missouri
United States	H. Lee Moffitt Cancer Center	Tampa	Florida
United States	University of Arizona Cancer Center	Tucson	Arizona
United States	Palm Beach Cancer Institute	West Palm Beach	Florida
United States	Wake Forest University School of Medicine	Winston Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
BioVex Limited	Amgen

Countries where clinical trial is conducted

United States,  Canada,  South Africa,  United Kingdom, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No
Secondary	Overall Survival	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.	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.	No
Secondary	Objective Response Rate	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.	From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months.	No
Secondary	Duration of Response	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.	From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months.	No
Secondary	Response Onset	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.	From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months.	No
Secondary	Time to Treatment Failure	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.	From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months.	No
Secondary	Response Interval	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.	From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months.	No