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A Study of Talimogene Laherparepvec in Stage IIIc and Stage IV Malignant Melanoma

This study has been completed.
Sponsor:
Collaborator:
Symbion Research International
Information provided by (Responsible Party):
BioVex Limited
ClinicalTrials.gov Identifier:
NCT00289016
First received: February 8, 2006
Last updated: November 12, 2015
Last verified: November 2015
  Purpose
The primary objective of the study was to assess the clinical efficacy of talimogene laherparepvec in terms of tumor response rates.

Condition Intervention Phase
Melanoma
Drug: Talimogene Laherparepvec
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of the Efficacy, Safety and Immunogenicity of OncoVEX^GM-CSF in Patients With Stage IIIc and Stage IV Malignant Melanoma

Resource links provided by NLM:


Further study details as provided by BioVex Limited:

Primary Outcome Measures:
  • Objective Tumor Response Rate [ Time Frame: From enrollment until the data cut-off date of 29 November 2008; Median duration of follow-up was 253 days ] [ Designated as safety issue: No ]

    Objective response rate is defined as the percentage of participants with an overall best response of complete response or partial response. The objective response to treatment was assessed by computed tomography (CT) scanning or other clinical measurement using modified Response Evaluation Criteria In Solid Tumors (RECIST). Responses must have been confirmed on two visits not less than 4 weeks apart.

    Tumor burden for a visit was calculated as the sum of the longest diameters of all tumors identified and measured up to that visit. Tumor response at each visit was derived from tumor burden, as follows:

    • Complete response (CR): zero tumor burden
    • Partial response (PR): a 30% or greater decrease in tumor burden
    • Progressive disease (PD): a 20% or greater increase in tumor burden
    • Stable disease (SD): none of the above (a < 30% decrease and < 20% increase in tumor burden)


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: From enrollment until the data cut-off date of 29 November 2008; Median duration of follow-up was 253 days ] [ Designated as safety issue: No ]
    Overall survival (OS) was calculated from the date of the first talimogene laherparepvec dose to the date of death. Median OS was estimated using the Kaplan-Meier method.

  • Time to Progression [ Time Frame: From enrollment until the data cut-off date of 29 November 2008; Median duration of follow-up was 253 days. ] [ Designated as safety issue: No ]

    Time to progression was calculated from the date of the first talimogene laherparepvec dose to the first date of documented progressive disease (via clinical symptom or tumor burden assessment) that was not followed by a later response of CR, PR, or stable disease.

    Median time to progression was calculated using the Kaplan-Meier method.


  • Time to Longest Continuous Response [ Time Frame: From enrollment until the data cut-off date of 29 November 2008; Median duration of follow-up was 253 days. ] [ Designated as safety issue: No ]
    Time to response was calculated from the date of the first talimogene laherparepvec dose to the initial date of the participant's last response interval.

  • Duration of Response [ Time Frame: From enrollment until the data cut-off date of 29 November 2008; Median duration of follow-up was 253 days. ] [ Designated as safety issue: No ]
    Duration of response was calculated from the initial date of response (CR or PR) until the date of progressive disease (or until last follow up that was CR or PR). Participants could have multiple response periods; in this situation, the last response interval was used for the calculation of duration of response.

  • Number of Participants With Adverse Events [ Time Frame: From first dose of talimogene laherparepvec until 30 days after the last dose; the median (minimum, maximum) duration of treatment was 82 (1, 346) days. ] [ Designated as safety issue: No ]

    The severity of an adverse event (AE) was graded according to Common Toxicity Criteria for Adverse Events (CTCAE) Version 3 (1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = death).

    Serious adverse events include death, life-threatening events, events requiring or prolonging hospitalization, result in persistent or significant disability/incapacity, or a congenital anomaly/birth defect, or otherwise important medical events that may jeopardise the patient or require intervention to prevent one of the above outcomes.



Enrollment: 50
Study Start Date: December 2005
Study Completion Date: May 2009
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Talimogene Laherparepvec
Participants received talimogene laherparepvec at an initial dose of 10⁶ plaque forming units (PFU)/mL injected into 1 or more tumors with maximum total volume of 4 mL (up to 2 mL per tumor). Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL began 3 weeks after the first dose and were administered every 2 weeks for up to 15 weeks. After the initial 8 doses, if indications of biological activity were observed, treatment could continue for up to 16 additional doses.
Drug: Talimogene Laherparepvec
Up to 4 mL of 10⁸ pfu/mL/per intratumoral injection
Other Names:
  • OncoVEX^GM-CSF
  • T-VEC
  • IMLYGIC

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with histologically proven stage IIIc (including two or more palpable lymph nodes, extracapsular or in-transit metastases) or stage IV melanoma that is not eligible for curative surgery and who have one or more tumors that are accessible for direct injection.
  2. Tumors 0.5 to 10 cm in the longest diameter that are suitable for injection (i.e. not bleeding or weeping).
  3. Serum lactate dehydrogenase (LDH) levels ≤ 2.0 times the upper limit of normal.
  4. Aged 18 years or more.
  5. Eastern Cooperative Oncology Group (ECOG) Performance status 0 or 1.
  6. Clinically immunocompetent.
  7. Recovered from prior therapy with at least 4 weeks since the last exposure to chemotherapy or radiotherapy.
  8. Total white cell count ≥ 3.0 x 10^9/L, platelet count ≥ 80 x 10^9/L.
  9. Serum creatinine ≤ 0.2 mmol/L.
  10. Bilirubin ≤ 1.5 times the upper limit of the normal range, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) equal to or less than twice the upper limit of the normal range and alkaline phosphatase equal to or less than twice the upper limit of the normal range.

Exclusion Criteria:

  1. Participation in any previous melanoma immunotherapy trial within one month prior to entry to this trial or any trial of any other investigational agent within the last month prior to entry to this trial.
  2. Tumors to be injected lying in mucosal regions or close to an airway, major blood vessel or spinal cord that, in the opinion of the Investigators, could cause occlusion or compression in the case of tumor swelling or erosion into a major vessel in the case of necrosis.
  3. Pregnancy, lactation or lack of effective contraception in women of child-bearing potential; lack of effective contraception in men if the partner is of child-bearing potential; women must have been practising an effective contraceptive method for at least three months prior to entry in to the trial (hormonal contraception or intrauterine device in conjunction with a barrier method OR surgically sterilised). Men must use a condom or be surgically sterilised.
  4. Major surgery within the 14 days prior to entry to the trial.
  5. Intercurrent serious infections within the 28 days prior to entry to the trial.
  6. Life-threatening illness unrelated to cancer.
  7. Treatment with antiviral agents within the 14 days prior to entry to the trial.
  8. Uncontrolled congestive cardiac failure.
  9. Clinically active autoimmune disease.
  10. Dermatoses involving or near to the tumors to be injected. Limb tumors may not be injected if active dermatoses are present on the same limb. Trunk and head and neck tumors must not be injected if dermatoses are present within 50 cm of the tumor.
  11. Known to test positive for human immunodeficiency virus (HIV), hepatitis B or C or syphilis.
  12. Patient only has injectable tumors that are not potentially resectable in the case of tumor necrosis or swelling.
  13. Previous history of malignancies of other types that have occurred or recurred within the previous 5 years with the exception of cone biopsied carcinoma of the cervix.
  14. Corticosteroid use.
  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: NCT00289016

Locations
United States, California
UCSD Cancer Center, Thornton Hospital
La Jolla, California, United States, 92093
UCLA
Los Angeles, California, United States, 90095
United States, Colorado
University of Colorado, Anschutz Cancer Pavillion
Aurora, Colorado, United States, 80010
United States, Minnesota
Hubert H Humphrey Cancer Center
Robbinsdale, Minnesota, United States, 55422
United States, New Jersey
Mountainside Hospital
Montclair, New Jersey, United States, 07042
United States, New York
Columbia University, Department of Surgery
New York, New York, United States, 10032
United States, Texas
Mary Crowely Medical Research Center
Dallas, Texas, United States, 75246
United Kingdom
Royal Marsden Hospital
London, United Kingdom, SW3 6JJ
Sponsors and Collaborators
BioVex Limited
Symbion Research International
Investigators
Principal Investigator: John Nemunaitis, MD Mary Crowley Medical Research Center
Study Director: Rob Coffin, PhD BioVex Limited
  More Information

Responsible Party: BioVex Limited
ClinicalTrials.gov Identifier: NCT00289016     History of Changes
Other Study ID Numbers: 002/03 
Study First Received: February 8, 2006
Results First Received: November 12, 2015
Last Updated: November 12, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by BioVex Limited:
gene transfer
gene therapy
oncolytic virus
GM-CSF
melanoma

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 09, 2016