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

Melanoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00289016
• Other study ID #: 002/03
• Status: Completed
• Phase: Phase 2
• First received: February 8, 2006
• Last updated: November 12, 2015
• Start date: December 2005
• Est. completion date: May 2009

Study information

• Verified date: November 2015
• Source: BioVex Limited
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The primary objective of the study was to assess the clinical efficacy of talimogene laherparepvec in terms of tumor response rates.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: May 2009
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma

Intervention

Drug:
• Talimogene Laherparepvec
Up to 4 mL of 108 pfu/mL/per intratumoral injection

Locations

Country	Name	City	State
United Kingdom	Royal Marsden Hospital	London
United States	University of Colorado, Anschutz Cancer Pavillion	Aurora	Colorado
United States	Mary Crowely Medical Research Center	Dallas	Texas
United States	UCSD Cancer Center, Thornton Hospital	La Jolla	California
United States	UCLA	Los Angeles	California
United States	Mountainside Hospital	Montclair	New Jersey
United States	Columbia University, Department of Surgery	New York	New York
United States	Hubert H Humphrey Cancer Center	Robbinsdale	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
BioVex Limited	Symbion Research International

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Tumor Response Rate	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)	From enrollment until the data cut-off date of 29 November 2008; Median duration of follow-up was 253 days	No
Secondary	Overall Survival	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.	From enrollment until the data cut-off date of 29 November 2008; Median duration of follow-up was 253 days	No
Secondary	Time to Progression	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.	From enrollment until the data cut-off date of 29 November 2008; Median duration of follow-up was 253 days.	No
Secondary	Time to Longest Continuous Response	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.	From enrollment until the data cut-off date of 29 November 2008; Median duration of follow-up was 253 days.	No
Secondary	Duration of Response	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.	From enrollment until the data cut-off date of 29 November 2008; Median duration of follow-up was 253 days.	No
Secondary	Number of Participants With Adverse Events	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.	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.	No