Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT02211131
Registration number
NCT02211131
Ethics application status
Date submitted
5/08/2014
Date registered
7/08/2014
Date last updated
5/06/2023
Titles & IDs
Public title
Efficacy and Safety of Talimogene Laherparepvec Neoadjuvant Treatment Plus Surgery Versus Surgery Alone for Melanoma
Query!
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
Query!
Secondary ID [1]
0
0
2014-001146-13
Query!
Secondary ID [2]
0
0
20110266
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Completely Resectable Stage IIIB, IIIC, or IVM1a Melanoma
0
0
Query!
Condition category
Condition code
Cancer
0
0
0
0
Query!
Malignant melanoma
Query!
Intervention/exposure
Study type
Interventional
Query!
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.
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Intervention code [2]
0
0
Treatment: Surgery
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Recurrence-Free Survival (RFS)
Query!
Assessment method [1]
0
0
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.
Query!
Timepoint [1]
0
0
24 months after last participant was randomized (data cutoff date of 30 April 2019)
Query!
Secondary outcome [1]
0
0
RFS
Query!
Assessment method [1]
0
0
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.
Query!
Timepoint [1]
0
0
5 years after the last participant was randomized (last subject last visit occurred 28 April 2022)
Query!
Secondary outcome [2]
0
0
Kaplan-Meier (K-M) Estimate of RFS Rate at 1 Year, 2 Years, 3 Years, and 5 Years
Query!
Assessment method [2]
0
0
Kaplan-Meier estimates of the percentage of participants with RFS at 1 year, 2 years, 3 years, and 5 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.
Query!
Timepoint [2]
0
0
5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022)
Query!
Secondary outcome [3]
0
0
Histopathology Tumor-Free Margin (R0) Surgical Resection Rate
Query!
Assessment method [3]
0
0
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.
Query!
Timepoint [3]
0
0
18 weeks after last participant randomized (data cutoff date of 30 April 2019)
Query!
Secondary outcome [4]
0
0
Pathological Complete Response (pCR) Rate
Query!
Assessment method [4]
0
0
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.
Query!
Timepoint [4]
0
0
18 weeks after last participant randomized (data cutoff date of 30 April 2019)
Query!
Secondary outcome [5]
0
0
Local Recurrence-Free Survival (LRFS)
Query!
Assessment method [5]
0
0
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.
Query!
Timepoint [5]
0
0
5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022)
Query!
Secondary outcome [6]
0
0
Regional Recurrence-Free Survival (RRFS)
Query!
Assessment method [6]
0
0
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.
Query!
Timepoint [6]
0
0
5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022)
Query!
Secondary outcome [7]
0
0
Distant Metastases-Free Survival (DMFS)
Query!
Assessment method [7]
0
0
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.
Query!
Timepoint [7]
0
0
5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022)
Query!
Secondary outcome [8]
0
0
Overall Survival (Kaplan-Meier)
Query!
Assessment method [8]
0
0
Overall Survival (OS) is defined as the time from randomization to the date of death due to any cause.
Query!
Timepoint [8]
0
0
5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022)
Query!
Secondary outcome [9]
0
0
Kaplan-Meier Estimate of OS at 1 Year, 2 Years, 3 Years, and 5 Years
Query!
Assessment method [9]
0
0
Kaplan-Meier estimates of the percentage of participants alive at 1 year, 2 years, 3 years, and 5 years from randomization.
Query!
Timepoint [9]
0
0
5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022)
Query!
Secondary outcome [10]
0
0
Best Overall Tumor Response Per Investigator Response Rate (Talimogene Laherparepvec Arm Only)
Query!
Assessment method [10]
0
0
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.
Query!
Timepoint [10]
0
0
18 months after last participant randomized (data cutoff date of 30 April 2019).
Query!
Secondary outcome [11]
0
0
Lesion Objective Response Rate: Injected Lesions (Talimogene Laherparepvec Arm Only)
Query!
Assessment method [11]
0
0
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%.
Query!
Timepoint [11]
0
0
18 months after last participant randomized (data cutoff date of 30 April 2019).
Query!
Secondary outcome [12]
0
0
Lesion Objective Response Rate: Uninjected Lesions (Talimogene Laherparepvec Arm Only)
Query!
Assessment method [12]
0
0
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%.
Query!
Timepoint [12]
0
0
18 months after last participant randomized (data cutoff date of 30 April 2019).
Query!
Secondary outcome [13]
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
Query!
Assessment method [13]
0
0
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 participant (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.
Query!
Timepoint [13]
0
0
Adverse Events are reported from first day of study drug or the surgery through 30 days after the last dose of study drug or 30 days after the surgery, whichever is later. Median duration of treatment was 11.14 weeks (range 0.1 to 12.3 weeks).
Query!
Secondary outcome [14]
0
0
Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions
Query!
Assessment method [14]
0
0
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 participant (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.
Query!
Timepoint [14]
0
0
Adverse 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.
Query!
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
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
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
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 2
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Completed
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
3/02/2015
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
28/04/2022
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
150
Query!
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Query!
Recruitment hospital [1]
0
0
Research Site - North Sydney
Query!
Recruitment hospital [2]
0
0
Research Site - Woodville South
Query!
Recruitment hospital [3]
0
0
Research Site - Heidelberg
Query!
Recruitment postcode(s) [1]
0
0
2060 - North Sydney
Query!
Recruitment postcode(s) [2]
0
0
5011 - Woodville South
Query!
Recruitment postcode(s) [3]
0
0
3084 - Heidelberg
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
Alabama
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
California
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
Florida
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
Kentucky
Query!
Country [5]
0
0
United States of America
Query!
State/province [5]
0
0
Massachusetts
Query!
Country [6]
0
0
United States of America
Query!
State/province [6]
0
0
Nebraska
Query!
Country [7]
0
0
United States of America
Query!
State/province [7]
0
0
New Jersey
Query!
Country [8]
0
0
United States of America
Query!
State/province [8]
0
0
New York
Query!
Country [9]
0
0
United States of America
Query!
State/province [9]
0
0
North Carolina
Query!
Country [10]
0
0
United States of America
Query!
State/province [10]
0
0
Ohio
Query!
Country [11]
0
0
United States of America
Query!
State/province [11]
0
0
Pennsylvania
Query!
Country [12]
0
0
United States of America
Query!
State/province [12]
0
0
Tennessee
Query!
Country [13]
0
0
United States of America
Query!
State/province [13]
0
0
Texas
Query!
Country [14]
0
0
United States of America
Query!
State/province [14]
0
0
Utah
Query!
Country [15]
0
0
Brazil
Query!
State/province [15]
0
0
Santa Catarina
Query!
Country [16]
0
0
Brazil
Query!
State/province [16]
0
0
São Paulo
Query!
Country [17]
0
0
Brazil
Query!
State/province [17]
0
0
Rio de Janeiro
Query!
Country [18]
0
0
France
Query!
State/province [18]
0
0
Dijon
Query!
Country [19]
0
0
France
Query!
State/province [19]
0
0
Marseille cedex 05
Query!
Country [20]
0
0
France
Query!
State/province [20]
0
0
Paris
Query!
Country [21]
0
0
France
Query!
State/province [21]
0
0
Pierre Benite Cedex
Query!
Country [22]
0
0
France
Query!
State/province [22]
0
0
Toulouse cedex 9
Query!
Country [23]
0
0
Greece
Query!
State/province [23]
0
0
Athens
Query!
Country [24]
0
0
Greece
Query!
State/province [24]
0
0
Heraklion - Crete
Query!
Country [25]
0
0
Poland
Query!
State/province [25]
0
0
Poznan
Query!
Country [26]
0
0
Poland
Query!
State/province [26]
0
0
Warszawa
Query!
Country [27]
0
0
Poland
Query!
State/province [27]
0
0
Wroclaw
Query!
Country [28]
0
0
Russian Federation
Query!
State/province [28]
0
0
Moscow
Query!
Country [29]
0
0
Russian Federation
Query!
State/province [29]
0
0
Saint-Petersburg
Query!
Country [30]
0
0
Spain
Query!
State/province [30]
0
0
Andalucía
Query!
Country [31]
0
0
Spain
Query!
State/province [31]
0
0
Navarra
Query!
Country [32]
0
0
Spain
Query!
State/province [32]
0
0
Madrid
Query!
Country [33]
0
0
Switzerland
Query!
State/province [33]
0
0
Chur
Query!
Country [34]
0
0
Switzerland
Query!
State/province [34]
0
0
Zürich
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Query!
Name
Amgen
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
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.
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT02211131
Query!
Trial related presentations / publications
Dummer R, Gyorki DE, Hyngstrom J, Berger AC, Conry R, Demidov L, Sharma A, Treichel SA, Radcliffe H, Gorski KS, Anderson A, Chan E, Faries M, Ross MI. Neoadjuvant talimogene laherparepvec plus surgery versus surgery alone for resectable stage IIIB-IVM1a melanoma: a randomized, open-label, phase 2 trial. Nat Med. 2021 Oct;27(10):1789-1796. doi: 10.1038/s41591-021-01510-7. Epub 2021 Oct 4.
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
MD
Query!
Address
0
0
Amgen
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT02211131
Download to PDF