Back to resultsAn Extended Use Study of Safety and Efficacy of Talimogene Laherparepvec in Melanoma
Primary Purpose
Melanoma
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Talimogene Laherparepvec
Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF)
Sponsored by
About this trial
This is an interventional treatment trial for Melanoma focused on measuring Melanoma, Stage IIIb, IIIc and IV Disease, oncolytic, OncoVex, OncoVEX^GM-CSF
Eligibility Criteria
Inclusion Criteria:
Previously participated in protocol 005/05 (NCT00769704) and:
- received the maximum number of talimogene laherparepvec treatment injections or cycles of GM-CSF allowable for that patient on study 005/05, or
- new injectable lesion(s) appeared after previous resolution of all injectable disease while on study 005/05. New injectable lesions must have appeared within ≤ 12 months from the End of Treatment visit on the 005/05 study.
- In the opinion of the investigator and the sponsor's medical monitor further treatment is warranted [e.g., those patients who do not have clinically relevant progressive disease (PDr)].
- Performance status (Eastern Cooperative Oncology Group, ECOG) 0 or 1.
- For patients randomized to talimogene laherparepvec only: Injectable disease (i.e. suitable for direct injection or through the use of ultrasound guidance) defined as at least 1 injectable cutaneous, subcutaneous or nodal melanoma lesion. There is no minimum size for injection.
Exclusion Criteria:
- Prior Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or 4 toxicity related to talimogene laherparepvec of any organ system (with the exception of injection site reactions, fever and vomiting).
- History of Grade 3 fatigue lasting > 1 week while on talimogene laherparepvec treatment.
- History of Grade 3 arthralgia/myalgias while on talimogene laherparepvec treatment.
- History of ≥ Grade 2 autoimmune reactions, allergic reactions or urticaria or other talimogene laherparepvec related non-hematological toxicities while on talimogene laherparepvec treatment that required a dose delay or discontinuation of talimogene laherparepvec therapy.
- PDr while participating in study 005/05
- Patient requested to be withdrawn from study 005/05 or was unable to comply with the demands of the 005/05 trial.
- At the discretion of the investigator, patient was withdrawn from the 005/05 trial.
Sites / Locations
- Rush University Medical Center
- Indiana University
- University of Iowa Hospitals & Clinics
- James Graham Brown Cancer Center
- Hubert H Humphrey Cancer Center
- University of North Carolina At Chapel Hill School of Medicine
- Mary Crowley Medical Research Center
- Huntsman Cancer Institute
- Oncology and Hematology Associates of Southwest Virginia, Inc.
- Royal Marsden Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
GM-CSF
Talimogene Laherparepvec
Arm Description
Granulocyte macrophage colony-stimulating factor (GM-CSF) was administered at a dose of 125 μg/m²/day subcutaneously for 14 consecutive days followed by 14 days of rest, in 28-day treatment cycles for up to 12 months or until a complete response, occurrence of an unacceptable toxicity, death or another criterion for withdrawal from treatment was met. Participants who demonstrated a partial response after being on treatment for 12 months could continue to be treated until disease progression or another treatment discontinuation criterion was met.
Talimogene laherparepvec was administered at a concentration of 10⁸ plaque forming units (PFU)/mL injected into 1 or more skin or subcutaneous tumors on Days 1 and 15 of each 28-day cycle for up to 12 months or until a complete response, occurrence of an unacceptable toxicity, death or another criterion for withdrawal from treatment was met. Participants who demonstrated a partial response after being on treatment for 12 months could continue to be treated until disease progression or another treatment discontinuation criterion was met.
Outcomes
Primary Outcome Measures
Number of Participants With Treatment-emergent Adverse Events (AEs)
AEs were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 based on the following guideline:
Grade 1: Mild AE; Grade 2: Moderate AE; Grade 3: Severe AE; Grade 4: Life-threatening or disabling AE; Grade 5: Death related to AE.
Treatment-related AE refers to AEs that have possible or probable relation to study treatment as determined by the investigator.
A serious AE is one that meets one or more of the following criteria/outcomes:
Results in death.
Is life-threatening.
Requires inpatient hospitalization or prolongation of existing hospitalization.
Results in persistent or significant disability/incapacity.
Is a congenital anomaly/birth defect.
Is an important medical event.
Secondary Outcome Measures
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 investigator. Best overall response for a patient is the best overall response observed across all time points and is cumulative (ie, includes responses during the parent study 005/05 and during Study 005/05-E).
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.
Durable Response Rate
Durable response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) assessed by the investigator, initiating at any time while receiving talimogene laherparepvec or GM-CSF therapy on the 005/05 or the 005/05-E study and maintained continuously for at least 6 months from response initiation. 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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01368276
Brief Title
An Extended Use Study of Safety and Efficacy of Talimogene Laherparepvec in Melanoma
Official Title
An Extension Protocol to Evaluate the Efficacy and Safety of Extended Use Treatment With OncoVEX^GM-CSF for Eligible Melanoma Patients Participating in Study 005/05
Study Type
Interventional
2. Study Status
Record Verification Date
November 2015
Overall Recruitment Status
Completed
Study Start Date
October 2010 (undefined)
Primary Completion Date
September 2014 (Actual)
Study Completion Date
September 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BioVex Limited
4. Oversight
5. Study Description
Brief Summary
The purpose of this study is to learn about the safety and the risks of using talimogene laherparepvec in patients who already received treatment with talimogene laherparepvec in study 005/05 (NCT00769704), and to see if extended treatment with talimogene laherparepvec can destroy melanoma tumors.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma
Keywords
Melanoma, Stage IIIb, IIIc and IV Disease, oncolytic, OncoVex, OncoVEX^GM-CSF
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
31 (Actual)
8. Arms, Groups, and Interventions
Arm Title
GM-CSF
Arm Type
Active Comparator
Arm Description
Granulocyte macrophage colony-stimulating factor (GM-CSF) was administered at a dose of 125 μg/m²/day subcutaneously for 14 consecutive days followed by 14 days of rest, in 28-day treatment cycles for up to 12 months or until a complete response, occurrence of an unacceptable toxicity, death or another criterion for withdrawal from treatment was met. Participants who demonstrated a partial response after being on treatment for 12 months could continue to be treated until disease progression or another treatment discontinuation criterion was met.
Arm Title
Talimogene Laherparepvec
Arm Type
Experimental
Arm Description
Talimogene laherparepvec was administered at a concentration of 10⁸ plaque forming units (PFU)/mL injected into 1 or more skin or subcutaneous tumors on Days 1 and 15 of each 28-day cycle for up to 12 months or until a complete response, occurrence of an unacceptable toxicity, death or another criterion for withdrawal from treatment was met. Participants who demonstrated a partial response after being on treatment for 12 months could continue to be treated until disease progression or another treatment discontinuation criterion was met.
Intervention Type
Biological
Intervention Name(s)
Talimogene Laherparepvec
Other Intervention Name(s)
OncoVEX^GM-CSF, IMLYGIC™
Intervention Description
Up to 4 mL of 10⁸ pfu/mL/per intratumoral injection
Intervention Type
Drug
Intervention Name(s)
Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF)
Intervention Description
125 µg/m² subcutaneous injection
Primary Outcome Measure Information:
Title
Number of Participants With Treatment-emergent Adverse Events (AEs)
Description
AEs were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 based on the following guideline:
Grade 1: Mild AE; Grade 2: Moderate AE; Grade 3: Severe AE; Grade 4: Life-threatening or disabling AE; Grade 5: Death related to AE.
Treatment-related AE refers to AEs that have possible or probable relation to study treatment as determined by the investigator.
A serious AE is one that meets one or more of the following criteria/outcomes:
Results in death.
Is life-threatening.
Requires inpatient hospitalization or prolongation of existing hospitalization.
Results in persistent or significant disability/incapacity.
Is a congenital anomaly/birth defect.
Is an important medical event.
Time Frame
From first administration of study drug in the extension period until 30 days after last dose. Median duration of treatment was 50 weeks in the GM-CSF group and 36 weeks in the talimogene laherparepvec group.
Secondary Outcome Measure Information:
Title
Objective Response Rate
Description
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 investigator. Best overall response for a patient is the best overall response observed across all time points and is cumulative (ie, includes responses during the parent study 005/05 and during Study 005/05-E).
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.
Time Frame
From randomization in study 005/05 until the data-cut-off date for the extension period of 08 August 2014; median treatment duration for 005/05 and 005/05-E studies combined was 88 weeks for talimogene laherparepvec and 100 weeks for GM-CSF.
Title
Durable Response Rate
Description
Durable response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) assessed by the investigator, initiating at any time while receiving talimogene laherparepvec or GM-CSF therapy on the 005/05 or the 005/05-E study and maintained continuously for at least 6 months from response initiation. 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.
Time Frame
From randomization in study 005/05 until the data-cut-off date for the extension period of 08 August 2014; median treatment duration for 005/05 and 005/05-E studies combined was 88 weeks for talimogene laherparepvec and 100 weeks for GM-CSF.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Previously participated in protocol 005/05 (NCT00769704) and:
received the maximum number of talimogene laherparepvec treatment injections or cycles of GM-CSF allowable for that patient on study 005/05, or
new injectable lesion(s) appeared after previous resolution of all injectable disease while on study 005/05. New injectable lesions must have appeared within ≤ 12 months from the End of Treatment visit on the 005/05 study.
In the opinion of the investigator and the sponsor's medical monitor further treatment is warranted [e.g., those patients who do not have clinically relevant progressive disease (PDr)].
Performance status (Eastern Cooperative Oncology Group, ECOG) 0 or 1.
For patients randomized to talimogene laherparepvec only: Injectable disease (i.e. suitable for direct injection or through the use of ultrasound guidance) defined as at least 1 injectable cutaneous, subcutaneous or nodal melanoma lesion. There is no minimum size for injection.
Exclusion Criteria:
Prior Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or 4 toxicity related to talimogene laherparepvec of any organ system (with the exception of injection site reactions, fever and vomiting).
History of Grade 3 fatigue lasting > 1 week while on talimogene laherparepvec treatment.
History of Grade 3 arthralgia/myalgias while on talimogene laherparepvec treatment.
History of ≥ Grade 2 autoimmune reactions, allergic reactions or urticaria or other talimogene laherparepvec related non-hematological toxicities while on talimogene laherparepvec treatment that required a dose delay or discontinuation of talimogene laherparepvec therapy.
PDr while participating in study 005/05
Patient requested to be withdrawn from study 005/05 or was unable to comply with the demands of the 005/05 trial.
At the discretion of the investigator, patient was withdrawn from the 005/05 trial.
Facility Information:
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Iowa Hospitals & Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
James Graham Brown Cancer Center
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Hubert H Humphrey Cancer Center
City
Robbinsdale
State/Province
Minnesota
ZIP/Postal Code
55422
Country
United States
Facility Name
University of North Carolina At Chapel Hill School of Medicine
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Mary Crowley Medical Research Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
Huntsman Cancer Institute
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Oncology and Hematology Associates of Southwest Virginia, Inc.
City
Salem
State/Province
Virginia
ZIP/Postal Code
24153
Country
United States
Facility Name
Royal Marsden Hospital
City
London
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom
12. IPD Sharing Statement
Links:
URL
http://www.biovex.com
Description
Sponsor Website
Learn more about this trial
An Extended Use Study of Safety and Efficacy of Talimogene Laherparepvec in Melanoma
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