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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02211131




Registration number
NCT02211131
Ethics application status
Date submitted
5/08/2014
Date registered
7/08/2014
Date last updated
28/05/2020

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)

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

Experimental: Talimogene Laherparepvec - Talimogene laherparepvec for 6 doses followed by 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
Recurrence-Free Survival (RFS) - Recurrence free survival (RFS) is defined as the time from randomization to the date of event, and is presented as a Kaplan Meier estimate of time to events. The event for RFS is defined as the first of local, regional, or distant recurrence of melanoma or death due to any cause. Participants without a histopathology tumor-free margin (R0) surgical outcome or those who withdrew prior to surgery were considered an event at randomization. Participants without an event were censored at their last evaluable tumor assessment.
Timepoint [1] 0 0
24 months after last participant randomized (data cutoff date of 30 April 2019)
Secondary outcome [1] 0 0
Kaplan-Meier (K-M) Estimate of RFS Rate at 1 Year and 2 Years - Kaplan-Meier estimates of the percentage of participants with RFS events at 1 year and 2 years from randomization. The event for RFS is defined as the first of local, regional, or distant recurrence of melanoma or death due to any cause. Participants without an R0 surgical outcome or those who withdrew prior to surgery are considered an event at randomization. Participants without an event were censored at their last evaluable tumor assessment. Rate is presented as the percentage of participants with RFS at given time point.
Timepoint [1] 0 0
1 year (Month 12), 2 years (Month 24)
Secondary outcome [2] 0 0
Histopathology Tumor-Free Margin (R0) Surgical Resection Rate - Histopathology tumor-free margin (R0) surgical resection is defined by pathologist as absence of ink on the tumor for all disease. Rate is presented as the percentage of participants with histopathology tumor-free margin (R0) surgical resection.
Timepoint [2] 0 0
18 weeks after last participant randomized (data cutoff date of 30 April 2019)
Secondary outcome [3] 0 0
Pathological Complete Response (pCR) Rate - Pathological Complete Response (pCR) is defined as no evidence of viable tumor cells on complete pathological evaluation of the surgical specimen per institutional standards of care. Rate is presented as the percentage of participants with pCR.
Timepoint [3] 0 0
18 weeks after last participant randomized (data cutoff date of 30 April 2019)
Secondary outcome [4] 0 0
Local Recurrence-Free Survival (LRFS) - Local recurrence-free survival (LRFS) is defined as the time from randomization to the earlier date of the first of local disease recurrence or death due to any cause. Participants without an R0 surgical outcome or those who withdrew prior to surgery are considered an event at randomization. Local recurrence is defined as histologically or cytologically confirmed reappearance of melanoma in the area of up to 2 cm from the scar from the surgical excision or at the edge of the skin graft if that was used for closure.
Timepoint [4] 0 0
24 months after last participant randomized (data cutoff date of 30 April 2019)
Secondary outcome [5] 0 0
Regional Recurrence-Free Survival (RRFS) - Regional recurrence-free survival (RRFS) is defined as the time from randomization to the date of the first of regional disease recurrence or death due to any cause. Participants without an R0 surgical outcome or those who withdrew prior to surgery are considered an event at randomization. Regional recurrence excludes local recurrence and is defined as histologically, cytologically, or radiographically confirmed reappearance of melanoma in the regional lymph node basin.
Timepoint [5] 0 0
24 months after last participant randomized (data cutoff date of 30 April 2019)
Secondary outcome [6] 0 0
Distant Metastases-Free Survival (DMFS) - Distant metastases-free survival (DMFS) is defined as the time from randomization to the date of the first of distant metastases or death due to any cause. Participants without an R0 surgical outcome or those who withdrew prior to surgery are considered an event at randomization. Distant metastases exclude local and regional recurrence and will include distant cutaneous/subcutaneous metastases, distant nodal metastases, or visceral, central nervous system, brain, or bone metastases.
Timepoint [6] 0 0
24 months after last participant randomized (data cutoff date of 30 April 2019)
Secondary outcome [7] 0 0
Overall Survival (OS) - Overall survival (OS) is defined as the time from randomization to the date of death due to any cause.
Timepoint [7] 0 0
24 months after last participant randomized (data cutoff date of 30 April 2019)
Secondary outcome [8] 0 0
Kaplan-Meier (K-M) Estimate of OS at 1 Year and 2 Years - Kaplan-Meier estimates of the percentage of participants with OS events at 1 year and 2 years from randomization. An OS event is defined as death due to any cause.
Timepoint [8] 0 0
1 year (Month 12), 2 years (Month 24)
Secondary outcome [9] 0 0
Best Overall Tumor Response Per Investigator Response Rate (Talimogene Laherparepvec Arm Only) - Response was assessed based on the response of the index lesions and nonindex lesions as described in protocol-defined World Health Organization (WHO) criteria (for complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD]), and presence or absence of new lesions. Best response for a participant is the best overall response observed across all time points. Response rate is reported as the percentage of participants with the best overall response (per investigator) of CR or PR. CR: complete disappearance of all index lesions, including any new measurable tumor lesions which might have appeared. PR: = 50% reduction in the sum of the products of the 2 largest perpendicular diameters of all index lesions and new measurable lesions, if applicable, at the time of assessment as compared to the sum of the products of the perpendicular diameters of all index lesions at baseline.
Timepoint [9] 0 0
18 months after last participant randomized (data cutoff date of 30 April 2019).
Secondary outcome [10] 0 0
Lesion Objective Response Rate: Injected Lesions (Talimogene Laherparepvec Arm Only) - The investigator-assessed tumor response rate for injected lesions, reported as the percentage of evaluable lesions in response. A lesion is in response if the decrease in tumor area is = 50%.
Timepoint [10] 0 0
18 months after last participant randomized (data cutoff date of 30 April 2019).
Secondary outcome [11] 0 0
Lesion Objective Response Rate: Uninjected Lesions (Talimogene Laherparepvec Arm Only) - The investigator-assessed tumor response rate for uninjected lesions, reported as the percentage of evaluable lesions in response. A lesion is in response if the decrease in tumor area is = 50%.
Timepoint [11] 0 0
18 months after last participant randomized (data cutoff date of 30 April 2019).
Secondary outcome [12] 0 0
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions - Adverse event (AE): any untoward medical occurrence that does not necessarily have a causal relationship with study treatment. SAE: AE meeting at least 1 of the following serious criteria: fatal; life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event. Event severity grades: 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening), 5 (death). Treatment begins when the first dose of protocol-required therapies is administered to a subject (Talimogene Laherparepvec Arm) or the participant undergoes surgery (Surgery Arm). Events are reported from first day of study drug or the surgery through 30 days after the last administration of talimogene laherparepvec or 30 days after the surgical resection of melanoma tumor lesion(s), whichever is later.
Timepoint [12] 0 0
Up to data cutoff date of 30 April 2019. Median duration of treatment for participants in the talimogene laherparepvec plus surgery group was 11.14 weeks (range 0.1 to 12.3 weeks).
Secondary outcome [13] 0 0
Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions - Adverse event (AE): any untoward medical occurrence that does not necessarily have a causal relationship with study treatment. SAE: AE meeting at least 1 of the following serious criteria: fatal; life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event. Event severity grades: 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening), 5 (death). Treatment begins when the first dose of protocol-required therapies is administered to a subject (Talimogene Laherparepvec Arm) or the participant undergoes surgery (Surgery Arm). Events are reported from first day of study drug or the surgery through 30 days after the last administration of talimogene laherparepvec or 30 days after the surgical resection of melanoma tumor lesion(s), whichever is later.
Timepoint [13] 0 0
Up to data cutoff date of 30 April 2019. Median duration of treatment for participants in the talimogene laherparepvec plus surgery group was 11.14 weeks (range 0.1 to 12.3 weeks).

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
Open (masking not 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
Accrual to date
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
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Kentucky
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Nebraska
Country [7] 0 0
United States of America
State/province [7] 0 0
New Jersey
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
Tennessee
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
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
Country [20] 0 0
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
Country [24] 0 0
Greece
State/province [24] 0 0
Heraklion - Crete
Country [25] 0 0
Poland
State/province [25] 0 0
Poznan
Country [26] 0 0
Poland
State/province [26] 0 0
Warszawa
Country [27] 0 0
Poland
State/province [27] 0 0
Wroclaw
Country [28] 0 0
Russian Federation
State/province [28] 0 0
Moscow
Country [29] 0 0
Russian Federation
State/province [29] 0 0
Saint-Petersburg
Country [30] 0 0
Spain
State/province [30] 0 0
Andalucía
Country [31] 0 0
Spain
State/province [31] 0 0
Navarra
Country [32] 0 0
Spain
State/province [32] 0 0
Madrid
Country [33] 0 0
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
https://clinicaltrials.gov/show/NCT02211131
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

Summary results
Other publications