Efficacy and safety of Talimogene Laherparepvec Neoadjuvant Treatment Plus Surgery versus Surgery alone for Melanoma

• Register: EUCTR
• Last refreshed on: 8 August 2022
• Main ID: EUCTR2014-001146-13-GR
• Date of registration: 07/08/2015
• Prospective Registration: Yes
• Primary sponsor: Amgen Inc.
• 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
• Date of first enrolment: 30/09/2015
• Target sample size: 102
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001146-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Brazil, Greece, Russian Federation, Spain, United States

Contacts

• Name: IHQ medical Info-Clinical Trials
• Affiliation: Amgen (EUROPE) GmbH

• Name: IHQ medical Info-Clinical Trials
• Affiliation: Amgen (EUROPE) GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
Male or female = 18 years of age with 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. Also, 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 76
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 74

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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Resectable, Stage IIIB to IVM1a Melanoma
MedDRA version: 18.0 Level: LLT Classification code 10053571 Term: Melanoma System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: Talimogene Laherparepvec
Product Code: AMG 678
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Talimogene laherparepvec
Current Sponsor code: AMG 678
Other descriptive name: TALIMOGENE LAHERPAREPVEC
Concentration unit: PFU/ml plaque forming unit(s)/millilitre
Concentration type: equal
Concentration number: 1000000-

Product Name: Talimogene Laherparepvec
Product Code: AMG 678
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Talimogene laherparepvec
Current Sponsor code: AMG 678
Other descriptive name: TALIMOGENE LAHERPAREPVEC
Concentration unit: PFU/ml plaque forming unit(s)/millilitre
Concentration type: equal
Concentration number: 100000000-

Primary Outcome(s)

Main Objective: To estimate the treatment effect of neoadjuvant talimogene laherparepvec plus surgery compared to surgery alone on recurrence-free survival (RFS).

Secondary Objective: To estimate the effect of:
- neoadjuvant talimogene laherparepvec plus surgery compared to surgery alone on 2-year, 3-year, and 5-year RFS
- neoadjuvant talimogene laherparepvec plus surgery compared to surgery alone on rate of histopathological tumor-free margin (R0) surgical resection
neoadjuvant talimogene laherparepvec on rate of pathological complete response (pCR)
- neoadjuvant talimogene laherparepvec plus surgery compared to surgery alone on local recurrence-free survival (LRFS) and distant metastases-free survival (DMFS)
- neoadjuvant talimogene laherparepvec plus surgery compared to surgery alone on 2-year, 3-year, 5-year, and overall survival (OS)
To estimate response to neoadjuvant talimogene laherparepvec overall and separately in injected and uninjected lesions during treatment (arm 1 only)
To evaluate the safety of neoadjuvant talimogene laherparepvec plus surgery compared to surgery alone

Primary end point(s): Recurrence-free survival (RFS)

Timepoint(s) of evaluation of this end point: The primary analyses for RFS will occur at the later time of either the occurrence of approximately 64 events (local or distant recurrence of melanoma or death) or approximately 2 years after end of randomization. The final analyses will occur approximately 5 years after end of randomization.

Secondary Outcome(s)

Secondary end point(s): 2-year, 3-year, and 5-year RFS
Rate of histopathology tumor-free margin (R0) surgical resection
Rate of pCR
LRFS
DMFS
2-year, 3-year and 5-year, and overall survival
Overall tumor response and tumor response in injected and uninjected lesions
Subject incidence of treatment-emergent and treatment-related adverse events

Timepoint(s) of evaluation of this end point: The primary analysis for certain secondary endpoints will be performed using the data from the second interim analysis. The final analyses will occur approximately 5 years after end of randomization.

Secondary ID(s)

20110266

2014-001146-13-ES

Source(s) of Monetary Support

Amgen Inc.

Ethics review

Status: Approved
Approval date: 30/09/2015
Contact: