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MelanomaPhase 3NCT00769704

Efficacy and Safety Study of Talimogene Laherparepvec Compared to Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) in Melanoma

A Phase 3 study testing Talimogene laherparepvec and GM-CSF in people with Melanoma, run by BioVex Limited at 83 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. 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 and GM-CSF
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
437 participants
Where
83 sitesin 4 countries
Study dates
Apr 2009to Sep 2014
Phase
Phase 3
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

  • 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

Who cannot join

  • 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

Trial locations and contacts

83 sites in 4 countries.

83 sites in 4 countries

United States57 sites

  • Texas Cancer Center, Abilene

    Abilene, Texas, 79701

  • New Mexico Cancer Care Alliance

    Albuquerque, New Mexico, 87109

  • Emory University

    Atlanta, Georgia, 30322

  • University of Colorado Cancer Center

    Aurora, Colorado, 80014

  • St Luke's Hospital & Health Network

    Bethlehem, Pennsylvania, 18015

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Gabrail Cancer Center

    Canton, Ohio, 44718

  • University of North Carolina At Chapel Hill School of Medicine

    Chapel Hill, North Carolina, 27599

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • Barrett Cancer Center

    Cincinnati, Ohio, 45267

  • Cleveland Clinic Foundation, Taussig Cancer Center

    Cleveland, Ohio, 44195

  • Mary Crowley Medical Research Center

    Dallas, Texas, 75246

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Institute for Translational Oncology Research

    Greenville, South Carolina, 29605

  • University of Texas - MD Anderson

    Houston, Texas, 77030

  • Indiana University

    Indianapolis, Indiana, 46202

  • Investigative Clinical Research of Indiana

    Indianapolis, Indiana, 46254

  • University of Iowa Hospitals & Clinics

    Iowa City, Iowa, 52242

  • Baptist Cancer Institute

    Jacksonville, Florida, 32207

  • University of Kansas Medical Center

    Kansas City, Kansas, 66205

  • Kansas City Cancer Center

    Kansas City, Missouri, 66210

  • University of California San Diego, Moores Cancer Center

    La Jolla, California, 92093

  • Lakeland Regional Cancer Center

    Lakeland, Florida, 33805

  • University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • UCLA Medical Center

    Los Angeles, California, 90095

  • James Graham Brown Cancer Center

    Louisville, Kentucky, 40202

  • University of Miami

    Miami, Florida, 33136

  • Mount Sinai Medical Center CCOP

    Miami Beach, Florida, 33140

  • Texas Oncology, Allison Cancer Center

    Midland, Texas, 79701

  • Aurora/St. Luke's Medical Center

    Milwaukee, Wisconsin, 53215

  • Mountainside Hospital

    Morristown, New Jersey, 07962

  • Intermountain Medical Center

    Murray, Utah, 84107

  • Vanderbilt Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Columbia Medical University

    New York, New York, 10032

  • Mount Sinai School of Medicine

    New York, New York, 10032

  • Methodist Estabrook Cancer Center

    Omaha, Nebraska, 68114

  • MD Anderson Cancer Center Orlando

    Orlando, Florida, 32806

  • Cancer Care Center at Lutheran General Hospital

    Park Ridge, Illinois, 60068

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

  • Earle A Chiles Research Institute, Providence Cancer Center

    Portland, Oregon, 97213

  • Rhode Island Hospital

    Providence, Rhode Island, 02905

  • Hubert H Humphrey Cancer Center

    Robbinsdale, Minnesota, 55422

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Oncology and Hematology Associates of Southwest Virginia, Inc.

    Salem, Virginia, 24153

  • Huntsman Cancer Institute

    Salt Lake City, Utah, 84112

  • San Francisco Oncology Associates

    San Francisco, California, 94115

  • Northern California Melanoma Center, St. Mary's Medical Center

    San Francisco, California, 94117

  • John Wayne Cancer Institute

    Santa Monica, California, 90404

  • Redwood Regional Medical Group Inc, North Bay Melanoma Program

    Sebastopol, California, 95472

  • St. Louis University Hospital

    St Louis, Missouri, 63110

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • H. Lee Moffitt Cancer Center

    Tampa, Florida, 33612

  • University of Arizona Cancer Center

    Tucson, Arizona, 85724

  • Palm Beach Cancer Institute

    West Palm Beach, Florida, 33401

  • Wake Forest University School of Medicine

    Winston-Salem, North Carolina, 27157

Other trials in United States

United Kingdom13 sites

  • University of Birmingham

    Birmingham, B15 2TT

  • Addenbrookes Hospital

    Cambridge, CB2 0QQ

  • Broomfield Hospital

    Chelmsford, CM1 7ET

  • St. James's University Hospital

    Leeds, LS9 7TF

  • Leicester Royal Infirmary

    Leicester, LE1 5WW

  • Royal Free Hospital

    London, NW3 2QG

  • St. George's University of London

    London, SW17 0RE

  • Royal Marsden Hospital

    London, SW3 6JJ

  • Clatterbridge Centre for Oncology

    Metropolitan Borough of Wirral, CH63 4JY

  • Freeman Hospital

    Newcastle upon Tyne, NE7 7DN

  • Nottingham City Hospital

    Nottingham, NG5 1PB

  • Churchill Hospital

    Oxford, OX3 7LJ

  • Southampton General Hospital

    Southampton, SO16 6YD

Other trials in United Kingdom

South Africa10 sites

  • Dr. Fourie & Bonnet

    Bloemfontein, Free State, 9301

  • GVI Onocology Clinical Trials Unit

    Cape Town, Western Cape, 7500

  • GVI Oncology Centre

    Cape Town, Western Cape

  • Wilgers Oncology Center

    Hatfield, Pretoria, 0028

  • Medical Oncology Centre of Rosebank

    Johannesburg, Gauteng, 2196

  • Wits Donald Gordon Clinical Trial Site

    Parktown, Guateng, 2193

  • Hopelands Cancer Centre

    Pietermaritzburg, KwaZulu-Natal, 3201

  • GVI Oncology

    Port Elizabeth, Eastern Cape, 6045

  • University of Pretoria

    Pretoria, Guateng, 0001

  • Mary Potter Oncology Centre

    Pretoria, Guateng, 0075

Other trials in South Africa

Canada3 sites

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

  • Jewish General Hospital

    Montreal, Quebec, H3T 1E2

  • Princess Margaret Hospital

    Toronto, Ontario, M5G2M9

Other trials in Canada

About this study

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

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.

Conditions
Melanoma
Being tested
Talimogene laherparepvec, GM-CSF
Keywords
Melanoma, OncoVEX^GM-CSF, GM-CSF, Stage IIIb, IIIc and IV Disease, oncolytic, OncoVex, T-Vec, talimogene laherparepvec
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Talimogene laherparepvecBiological

    Also called OncoVEX^GM-CSF, IMLYGIC™

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

  • GM-CSFBiological

    Also called Leukine, Sargramostim

    125 µg/m² subcutaneous injection

Study groups in NCT00769704
Study groupRoleWhat they receive
GM-CSFActive comparatorGranulocyte 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.
Receives: Biological: GM-CSF
Talimogene LaherparepvecExperimentalParticipants 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.
Receives: Biological: Talimogene laherparepvec

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Durable Response Rate

    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.

    Measured: From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months.

Secondary outcomes (6)

  1. Overall Survival

    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.

    Measured: 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.

  2. Objective Response Rate

    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.

    Measured: From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months.

  3. Duration of Response

    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.

    Measured: From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months.

  4. Response Onset

    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.

    Measured: From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months.

  5. Time to Treatment Failure

    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.

    Measured: From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months.

  6. Response Interval

    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.

    Measured: From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Oct 2008 (estimated)
  2. Study startApr 2009
  3. Primary completionFeb 2013
  4. Study completionSep 2014

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
437 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00769704
Sponsor's protocol ID
005/05
Other IDs
20110263, 2008-006140-20, 2008
Status last verified
Jun 2016
First submitted
7 Oct 2008
Last updated
13 Jul 2016
Data monitoring committee
Yes

Publications

  • Andtbacka RH, Kaufman HL, Collichio F, Amatruda T, Senzer N, Chesney J, Delman KA, Spitler LE, Puzanov I, Agarwala SS, Milhem M, Cranmer L, Curti B, Lewis K, Ross M, Guthrie T, Linette GP, Daniels GA, Harrington K, Middleton MR, Miller WH Jr, Zager JS, Ye Y, Yao B, Li A, Doleman S, VanderWalde A, Gansert J, Coffin RS. Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma. J Clin Oncol. 2015 Sep 1;33(25):2780-8. doi: 10.1200/JCO.2014.58.3377. Epub 2015 May 26.

    PubMed 26014293

  • Andtbacka RHI, Collichio F, Harrington KJ, Middleton MR, Downey G, Ӧhrling K, Kaufman HL. Final analyses of OPTiM: a randomized phase III trial of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in unresectable stage III-IV melanoma. J Immunother Cancer. 2019 Jun 6;7(1):145. doi: 10.1186/s40425-019-0623-z.

    PubMed 31171039

  • Kaufman HL, Andtbacka RHI, Collichio FA, Wolf M, Zhao Z, Shilkrut M, Puzanov I, Ross M. Durable response rate as an endpoint in cancer immunotherapy: insights from oncolytic virus clinical trials. J Immunother Cancer. 2017 Sep 19;5(1):72. doi: 10.1186/s40425-017-0276-8.

    PubMed 28923101

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Talimogene laherparepvec and GM-CSF in people with Melanoma, run by BioVex Limited at 83 sites in 4 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 7 inclusion and 2 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 13 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 83 sites in United States, United Kingdom, South Africa, Canada. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 17 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?

Durable Response Rate (time frame: From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00769704, which also lists 3 linked publications.

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 13 Jul 2016.

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