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

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Talimogene Laherparepvec

About this trial

This is an interventional treatment trial for Melanoma focused on measuring gene transfer, gene therapy, oncolytic virus, GM-CSF, melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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. Tumors 0.5 to 10 cm in the longest diameter that are suitable for injection (i.e. not bleeding or weeping). Serum lactate dehydrogenase (LDH) levels ≤ 2.0 times the upper limit of normal. Aged 18 years or more. Eastern Cooperative Oncology Group (ECOG) Performance status 0 or 1. Clinically immunocompetent. Recovered from prior therapy with at least 4 weeks since the last exposure to chemotherapy or radiotherapy. Total white cell count ≥ 3.0 x 10^9/L, platelet count ≥ 80 x 10^9/L. Serum creatinine ≤ 0.2 mmol/L. 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: 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. 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. 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. Major surgery within the 14 days prior to entry to the trial. Intercurrent serious infections within the 28 days prior to entry to the trial. Life-threatening illness unrelated to cancer. Treatment with antiviral agents within the 14 days prior to entry to the trial. Uncontrolled congestive cardiac failure. Clinically active autoimmune disease. 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. Known to test positive for human immunodeficiency virus (HIV), hepatitis B or C or syphilis. Patient only has injectable tumors that are not potentially resectable in the case of tumor necrosis or swelling. 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. Corticosteroid use.

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Talimogene Laherparepvec

Arm Description

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.

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT00289016

First Posted

February 8, 2006

Last Updated

November 12, 2015

Sponsor

BioVex Limited

Collaborators

Symbion Research International

1. Study Identification

Unique Protocol Identification Number

NCT00289016

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2015

Overall Recruitment Status

Completed

Study Start Date

December 2005 (undefined)

Primary Completion Date

December 2008 (Actual)

Study Completion Date

May 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

BioVex Limited

Collaborators

Symbion Research International

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Melanoma

Keywords

gene transfer, gene therapy, oncolytic virus, GM-CSF, melanoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

50 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Talimogene Laherparepvec

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Talimogene Laherparepvec

Other Intervention Name(s)

OncoVEX^GM-CSF, T-VEC, IMLYGIC

Intervention Description

Up to 4 mL of 10⁸ pfu/mL/per intratumoral injection

Primary Outcome Measure Information:

Title

Objective Tumor Response Rate

Description

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)

Time Frame

From enrollment until the data cut-off date of 29 November 2008; Median duration of follow-up was 253 days

Secondary Outcome Measure Information:

Title

Overall Survival

Description

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 Frame

From enrollment until the data cut-off date of 29 November 2008; Median duration of follow-up was 253 days

Title

Time to Progression

Description

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 Frame

From enrollment until the data cut-off date of 29 November 2008; Median duration of follow-up was 253 days.

Title

Time to Longest Continuous Response

Description

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.

Time Frame

From enrollment until the data cut-off date of 29 November 2008; Median duration of follow-up was 253 days.

Title

Duration of Response

Description

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.

Time Frame

From enrollment until the data cut-off date of 29 November 2008; Median duration of follow-up was 253 days.

Title

Number of Participants With Adverse Events

Description

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.

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.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria: 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. Tumors 0.5 to 10 cm in the longest diameter that are suitable for injection (i.e. not bleeding or weeping). Serum lactate dehydrogenase (LDH) levels ≤ 2.0 times the upper limit of normal. Aged 18 years or more. Eastern Cooperative Oncology Group (ECOG) Performance status 0 or 1. Clinically immunocompetent. Recovered from prior therapy with at least 4 weeks since the last exposure to chemotherapy or radiotherapy. Total white cell count ≥ 3.0 x 10^9/L, platelet count ≥ 80 x 10^9/L. Serum creatinine ≤ 0.2 mmol/L. 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: 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. 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. 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. Major surgery within the 14 days prior to entry to the trial. Intercurrent serious infections within the 28 days prior to entry to the trial. Life-threatening illness unrelated to cancer. Treatment with antiviral agents within the 14 days prior to entry to the trial. Uncontrolled congestive cardiac failure. Clinically active autoimmune disease. 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. Known to test positive for human immunodeficiency virus (HIV), hepatitis B or C or syphilis. Patient only has injectable tumors that are not potentially resectable in the case of tumor necrosis or swelling. 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. Corticosteroid use.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

John Nemunaitis, MD

Organizational Affiliation

Mary Crowley Medical Research Center

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Rob Coffin, PhD

Organizational Affiliation

BioVex Limited

Official's Role

Study Director

Facility Information:

Facility Name

UCSD Cancer Center, Thornton Hospital

City

La Jolla

State/Province

California

ZIP/Postal Code

92093

Country

United States

Facility Name

UCLA

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

Facility Name

University of Colorado, Anschutz Cancer Pavillion

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80010

Country

United States

Facility Name

Hubert H Humphrey Cancer Center

City

Robbinsdale

State/Province

Minnesota

ZIP/Postal Code

55422

Country

United States

Facility Name

Mountainside Hospital

City

Montclair

State/Province

New Jersey

ZIP/Postal Code

07042

Country

United States

Facility Name

Columbia University, Department of Surgery

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

Facility Name

Mary Crowely Medical Research Center

City

Dallas

State/Province

Texas

ZIP/Postal Code

75246

Country

United States

Facility Name

Royal Marsden Hospital

City

London

ZIP/Postal Code

SW3 6JJ

Country

United Kingdom

Melanoma

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial