MelanomaPhase 2NCT00289016
A Study of Talimogene Laherparepvec in Stage IIIc and Stage IV Malignant Melanoma
A Phase 2 study testing Talimogene Laherparepvec in people with Melanoma, run by BioVex Limited at 8 sites in 2 countries.
Trial summary
The primary objective of the study was to assess the clinical efficacy of talimogene laherparepvec in terms of tumor response rates. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- Talimogene Laherparepvec
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 8 sitesin 2 countries
- Study dates
- Dec 2005to May 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
United States7 sites
University of Colorado, Anschutz Cancer Pavillion
Aurora, Colorado, 80010
Mary Crowely Medical Research Center
Dallas, Texas, 75246
UCSD Cancer Center, Thornton Hospital
La Jolla, California, 92093
UCLA
Los Angeles, California, 90095
Mountainside Hospital
Montclair, New Jersey, 07042
Columbia University, Department of Surgery
New York, New York, 10032
Hubert H Humphrey Cancer Center
Robbinsdale, Minnesota, 55422
About this study
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
The primary objective of the study was to assess the clinical efficacy of talimogene laherparepvec in terms of tumor response rates.
- Conditions
- Melanoma
- Being tested
- Talimogene Laherparepvec
- Keywords
- gene transfer, gene therapy, oncolytic virus, GM-CSF, melanoma
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Talimogene LaherparepvecDrug
Also called OncoVEX^GM-CSF, T-VEC, IMLYGIC
Up to 4 mL of 10⁸ pfu/mL/per intratumoral injection
| Study group | Role | What they receive |
|---|---|---|
| Talimogene Laherparepvec | Experimental | 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. Receives: Drug: Talimogene Laherparepvec |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: From enrollment until the data cut-off date of 29 November 2008; Median duration of follow-up was 253 days
Secondary outcomes (5)
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.
Measured: From enrollment until the data cut-off date of 29 November 2008; Median duration of follow-up was 253 days
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.
Measured: From enrollment until the data cut-off date of 29 November 2008; Median duration of follow-up was 253 days.
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.
Measured: From enrollment until the data cut-off date of 29 November 2008; Median duration of follow-up was 253 days.
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.
Measured: From enrollment until the data cut-off date of 29 November 2008; Median duration of follow-up was 253 days.
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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2006 (estimated)
- Study startDec 2005
- Primary completionDec 2008
- Study completionMay 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioVex Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Symbion Research International
- Responsible party
- Sponsor
- Investigators
- John Nemunaitis, MD, Principal investigator, Mary Crowley Medical Research CenterRob Coffin, PhD, Study director, BioVex Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00289016
- Sponsor's protocol ID
- 002/03
- Status last verified
- Nov 2015
- First submitted
- 8 Feb 2006
- Last updated
- 18 Dec 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00289016
- Acronym / sponsor ID
- 002/03
- Conditions
- Melanoma
- Keywords
- gene transfer, gene therapy, oncolytic virus, GM-CSF, melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- BioVex LimitedIndustry (pharma, biotech, devices)
- Collaborators
- Symbion Research International
- Study start
- Dec 2005
- Primary completion
- Dec 2008 (actual)
- Study completion
- May 2009 (actual)
- First posted
- 9 Feb 2006 (estimated)
- Results
- Posted 18 Dec 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of the study was to assess the clinical efficacy of talimogene laherparepvec in terms of tumor response rates.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Talimogene Laherparepvec | Experimental | Drug: Talimogene LaherparepvecParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Talimogene LaherparepvecAlso: OncoVEX^GM-CSF, T-VEC, IMLYGICUp to 4 mL of 10⁸ pfu/mL/per intratumoral injection | Drug | Talimogene Laherparepvec |
Primary outcome
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
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)
5 secondary outcomes
Overall Survival
Time frame: From enrollment until the data cut-off date of 29 November 2008; Median duration of follow-up was 253 days
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.
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.
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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John Nemunaitis, MD principal investigator
Mary Crowley Medical Research Center
Rob Coffin, PhD study director
BioVex Limited
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Talimogene Laherparepvec in people with Melanoma, run by BioVex Limited at 8 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Dec 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2015.