Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

  Show 83 Study Locations
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 December 08, 2016