Trial from ClinicalTrials.gov

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Trial ID
NCT02211131
Ethics application status
Date submitted
5/08/2014
Date registered
5/08/2014
Date last updated
12/06/2017

Titles & IDs
Public title
Efficacy and Safety of Talimogene Laherparepvec Neoadjuvant Treatment Plus Surgery Versus Surgery Alone for Melanoma
Scientific title
A Phase 2, Multicenter, Randomized, Open-label Trial Assessing the Efficacy and Safety of Talimogene Laherparepvec Neoadjuvant Treatment Plus Surgery Versus Surgery Alone for Resectable, Stage IIIB to IVM1a Melanoma
Secondary ID [1] 0 0
2014-001146-13
Secondary ID [2] 0 0
20110266
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Completely Resectable Stage IIIB, IIIC, or IVM1a Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: drugs - Talimogene Laherparepvec
Treatment: surgery - Immediate surgical resection of melanoma lesion(s)

Experimental: Talimogene Laherparepvec - Arm 1 Talimogene laherparepvec for 6 doses followed by surgical resection of melanoma tumor lesion(s).

Other: Surgery - Arm 2: Surgical resection of melanoma tumor lesion(s)


Treatment: drugs: Talimogene Laherparepvec
Talimogene laherparepvec will be administered by intralesional injection into the injectable cutaneous, subcutaneous, and nodal tumors initially at a dose of 10^6 plaque forming units (PFU)/mL at day 1 of week 1 followed by a dose of 10^8 PFU/mL at day 1 (±3 days) of week 4, 6, 8, 10 and 12 or until all injectable tumors have disappeared, or intolerance of study treatment or in the opinion of the investigator, immediate surgical resection or any other treatment for melanoma is warranted, whichever occurs first.

Treatment: surgery: Immediate surgical resection of melanoma lesion(s)
Surgical resection of melanoma tumor lesion(s) will be performed after randomization any time during weeks 1 to 6.

Intervention code [1] 0 0
Treatment: drugs
Intervention code [2] 0 0
Treatment: surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Efficacy - Estimate the efficacy of neoadjuvant talimogene laherparepvec plus surgery versus surgery alone on recurrence-free survivial (RFS)
Timepoint [1] 0 0
24 months after last patient randomized
Secondary outcome [1] 0 0
Efficacy - Estimate the efficacy of neoadjuvant talimogene laherparepvec plus surgery compared to surgery alone on 2-year, 3-year and 5-year RFS
Timepoint [1] 0 0
Primary analysis for 2-year RFS will occur approximately 2 years after the end of randomisation. Additional analysis for 3-year RFS and final analysis for 5-year RFS will occur approximately 3 and 5 years after the end of randomization
Secondary outcome [2] 0 0
Efficacy - Estimate the efficacy of neoadjuvant talimogene laherparepvec plus surgery compared to surgery alone on rate of histopathological tumor-free margin (R0) surgical resection
Timepoint [2] 0 0
16 weeks after last patient randomized
Secondary outcome [3] 0 0
Efficacy - Estimate the effect of neoadjuvant talimogene laherparepvec on rate of pathological complete response (pCR)
Timepoint [3] 0 0
16 weeks after last patient randomized
Secondary outcome [4] 0 0
Efficacy - Estimate the effect of neoadjuvant talimogene laherparepvec plus surgery compared to surgery alone on local recurrence-free survival (LRFS) and distant metastases-free survival (DMFS)
Timepoint [4] 0 0
24 months after last patient randomized
Secondary outcome [5] 0 0
Efficacy - Estimate the effect of neoadjuvant talimogene laherparepvec plus surgery compared to surgery alone on 2-year, 3-year, 5-year and overall survival (OS)
Timepoint [5] 0 0
Primary analysis for 2 year overall survival will occur approximately 2 years after the end of randomisation. Additional analysis for 3-year OS and final analysis for 5-year OS will occur approximately 3 and 5 years after the end of randomization
Secondary outcome [6] 0 0
Overall Response - Estimate response to neoadjuvant talimogene laherparepvec overall and seperately in injected and uninjected lesions during treatment (Arm 1 only)
Timepoint [6] 0 0
16 weeks after last patient randomized
Secondary outcome [7] 0 0
Safety - Evaluate the safety of neoadjuvant talimogene laherparepvec plus surgery commpared to surgery alone
Timepoint [7] 0 0
16 weeks after 40tth, 75th and last patient randomized

Eligibility
Key inclusion criteria
- Histologically confirmed diagnosis of stage IIIB, IIIC or IVM1a melanoma eligible for
complete surgical resection.

- Prior systemic, regional and radiation anticancer therapies for melanoma must have
been completed at least 3 months prior to randomization.

- Subject must have measurable disease and must be a candidate for intralesional therapy
with at least one injectable cutaneous, subcutaneous, or nodal melanoma lesion (= 10
mm in longest diameter) or with multiple injectable lesions that in aggregate have a
longest diameter of = 10 mm.

- Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0
or 1 and must have a serum lactate dehydrogenase (LDH) = 1.0 X upper limit of normal
and adequate hematologic, hepatic, renal, and coagulation organ function- Other
criteria may apply
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Subject must not have primary ocular or mucosal melanoma, or history or evidence of
melanoma associated with immunodeficiency states (eg, hereditary immune deficiency,
organ transplant, or leukemia).

- Subject must not have history or evidence of symptomatic autoimmune pneumonitis,
glomerulonephritis, vasculitis, or other symptomatic autoimmune disease.

- Subject must not have evidence of clinically significant immunosuppression or active
herpetic skin lesions or prior complications of herpes simplex type 1 (HSV-1)
infection (eg, herpetic keratitis or encephalitis) and must not require intermittent
or chronic systemic treatment with an antiherpetic drug (eg, acyclovir), other than
intermittent topical use.

- Subject known to have acute or chronic active hepatitis B, hepatitis C, or human
immunodeficiency virus infection will also be excluded.

- Subject must not have been treated previously with talimogene laherparepvec or tumor
vaccine.

Other criteria may apply

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Current
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Research Site - North Sydney
Recruitment hospital [2] 0 0
Research Site - Woodville South
Recruitment hospital [3] 0 0
Research Site - Heidelberg
Recruitment postcode(s) [1] 0 0
2060 - North Sydney
Recruitment postcode(s) [2] 0 0
5011 - Woodville South
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
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California
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United States of America
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Florida
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United States of America
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Kentucky
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United States of America
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Massachusetts
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United States of America
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Nebraska
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United States of America
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New Jersey
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United States of America
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New York
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United States of America
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North Carolina
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United States of America
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Ohio
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United States of America
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Pennsylvania
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United States of America
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Tennessee
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United States of America
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Texas
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United States of America
State/province [14] 0 0
Utah
Country [15] 0 0
Brazil
State/province [15] 0 0
Santa Catarina
Country [16] 0 0
Brazil
State/province [16] 0 0
São Paulo
Country [17] 0 0
Brazil
State/province [17] 0 0
Rio de Janeiro
Country [18] 0 0
France
State/province [18] 0 0
Dijon
Country [19] 0 0
France
State/province [19] 0 0
Marseille cedex 05
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France
State/province [20] 0 0
Paris
Country [21] 0 0
France
State/province [21] 0 0
Pierre Benite Cedex
Country [22] 0 0
France
State/province [22] 0 0
Toulouse cedex 9
Country [23] 0 0
Greece
State/province [23] 0 0
Athens
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Greece
State/province [24] 0 0
Heraklion - Crete
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Poland
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Poznan
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Poland
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Warszawa
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Poland
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Wroclaw
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Russian Federation
State/province [28] 0 0
Moscow
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Russian Federation
State/province [29] 0 0
Saint-Petersburg
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Spain
State/province [30] 0 0
Andalucía
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Spain
State/province [31] 0 0
Navarra
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Spain
State/province [32] 0 0
Madrid
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Switzerland
State/province [33] 0 0
Chur
Country [34] 0 0
Switzerland
State/province [34] 0 0
Zürich

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a phase 2, multicenter, randomized, open-label study to estimate the efficacy of
talimogene laherparepvec as a neoadjuvant treatment followed by surgery compared to surgery
alone in subjects with completely resectable stage IIIB, IIIC, or IVM1a melanoma.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries
Contact person responsible for updating information