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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
Results First Received: September 22, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Melanoma
Interventions: Biological: Talimogene laherparepvec
Biological: GM-CSF

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations

Eligible patients were adults with histologically confirmed, not surgically resectable, stage IIIB - IV melanoma suitable for direct or ultrasound-guided injection.

Among those randomized, the first patient enrolled 29 April 2009 and last patient enrolled 8 June 2011.

1 patient randomized 3 times is counted once under talimogene laherparepvec.


Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Patients were assigned at a 2:1 ratio using central random assignment to receive intralesional talimogene laherparepvec or subcutaneous granulocyte macrophage colony-stimulating factor (GM-CSF). Randomization was stratified by site of first recurrence, presence of liver metastases, disease stage, and prior nonadjuvant systemic treatment.

Reporting Groups
  Description
GM-CSF Granulocyte macrophage colony-stimulating factor (GM-CSF) was administered at a dose of 125 μg/m²/day subcutaneously for 14 days in 28-day cycles 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 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.

Participant Flow:   Overall Study
    GM-CSF   Talimogene Laherparepvec
STARTED   141   296 
Intent-to-treat Population   141 [1]   295 [2] 
Received Treatment   127   292 
COMPLETED   30   97 
NOT COMPLETED   111   199 
Lost to Follow-up                3                2 
Death                95                190 
Withdrawal by Subject                12                5 
Other                1                2 
[1] All participants who were randomized once to study treatment
[2] Participants who were randomized once to study treatment; excludes 1 participant randomized 3 times



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
GM-CSF GM-CSF was administered at a dose of 125 μg/m²/day subcutaneously for 14 days in 28-day cycles 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 Participants received talimogene laherparepvec on Days 1 and 15 of each 28-day cycle for 24 weeks. The initial dose was at a concentration of 10⁶ 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.
Total Total of all reporting groups

Baseline Measures
   GM-CSF   Talimogene Laherparepvec   Total 
Overall Participants Analyzed 
[Units: Participants]
 141   296   437 
Age 
[Units: Years]
Mean (Standard Deviation)
 62.92  (14.13)   63.07  (13.68)   63.03  (13.81) 
Gender 
[Units: Participants]
     
Female   64   123   187 
Male   77   173   250 
Race/Ethnicity, Customized 
[Units: Participants]
     
White   138   290   428 
Black   2   1   3 
Asian   0   1   1 
Native Hawaiian or Other Pacific Islander   0   1   1 
Other   1   3   4 
Eastern Cooperative Oncology Group (ECOG) Performance Status [1] 
[Units: Participants]
     
 97   210   307 
 32   82   114 
Missing   12   4   16 
[1] Scale used to assess how a patient's disease is progressing, how the disease affects the daily living abilities of the patient: 0 = Fully active, able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity, ambulatory, able to carry out work of a light nature; 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about > 50% of waking hours; 3 = Capable of only limited self care, confined to a bed or chair > 50% of waking hours; 4 = Completely disabled, confined to bed or chair; 5 = Dead.
Tumor, Node, Metastasis (TNM) Disease Stage [1] 
[Units: Participants]
     
Stage IIIB   12   22   34 
Stage IIIC   31   66   97 
Stage IV M1a   43   76   119 
Stage IV M1b   26   64   90 
Stage IV M1c   29   67   96 
Missing   0   1   1 
[1] Stage IIIB: Ulcerated lesion and 1 lymph node or 2-3 nodes with micrometastasis, or any-depth lesion with no ulceration, and 1 lymph node or 2-3 nodes with macrometastasis; Stage IIIC: Ulcerated lesion and 1 lymph node with macrometastasis; 2-3 nodes with macrometastasis or ≥4 metastatic lymph nodes, matted lymph nodes, or in-transit met(s)/satellite(s); Stage IV: M1a: Spread to skin, subcutaneous tissue, or lymph nodes; normal lactate dehydrogenase (LDH) level; M1b: Spread to lungs, normal LDH; M1c: Spread to all other visceral organs, normal LDH or any distant disease with elevated LDH.
Line of Therapy 
[Units: Participants]
     
First Line   65   138   203 
Second Line or Greater   76   158   234 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Durable Response Rate   [ Time Frame: From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months. ]

2.  Secondary:   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. ]

3.  Secondary:   Objective Response Rate   [ Time Frame: From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months. ]

4.  Secondary:   Duration of Response   [ Time Frame: From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months. ]

5.  Secondary:   Response Onset   [ Time Frame: From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months. ]

6.  Secondary:   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. ]

7.  Secondary:   Response Interval   [ Time Frame: From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months. ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Amgen, Inc.
phone: 866-572-6436


Publications of Results:

Responsible Party: BioVex Limited
ClinicalTrials.gov Identifier: NCT00769704     History of Changes
Other Study ID Numbers: 005/05
20110263 ( Other Identifier: Sponsor )
2008-006140-20 ( EudraCT Number )
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