Study of Talimogene Laherparepvec In Children With Advanced Non CNS Tumors
- Registration Number
- NCT02756845
- Lead Sponsor
- Amgen
- Brief Summary
This is a phase 1 study to evaluate the safety of intralesional talimogene laherparepvec administration in pediatric subjects with advanced non-CNS tumors that are amenable to direct injection
- Detailed Description
This is a phase 1, multicenter, open-label study of talimogene laherparepvec in pediatric subjects with advanced non-CNS tumors that are amenable to direct injection in the clinical setting. Approximately 18 - 24 pediatric subjects are expected to be enrolled and treated with at least 1 dose of talimogene laherparepvec into 2 cohorts stratified by age. DLT will be evaluated based on at least 9 DLT-evaluable subjects in cohort A1. The DLT evaluation period is 35 days from the initial administration of talimogene laherparepvec.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 15
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Talimogene Laherparepvec (TVEC) Talimogene Laherparepvec The first dose of talimogene laherparepvec will be administered at a dose of up to 4.0 mL of 10ᶺ6 PFU/mL followed by a dose of up to 4.0 mL of 10ᶺ8 PFU/mL 21 days (+3 days) later. Subsequent doses of up to 4.0 mL of 10ᶺ8 PFU/mL will be administered every 14 days (± 3 days) thereafter. Cohorts will be assigned as follows: Cohort A1 (age 12 to ≤ 21 years). Cohort B1 (age 2 to \< 12 years). The DLRT will review the safety data of the first 3 subjects in the older age cohort A1 to decide if the younger age cohort B1 can be opened for enrollment. If dose de-escalation is needed and if permissible based on the incidence of DLTs, additional DLT-evaluable subjects will be enrolled and treated at a lower dose level of talimogene laherparepvec. Dose de-escalation cohorts will be assigned as follows and the same DLT rules will be applied: Cohort A2 (age 12 to ≤ 21 years), Cohort B2 (age 2 to \< 12 years).
- Primary Outcome Measures
Name Time Method Percentage of Participants Who Experienced a Dose-limiting Toxicity (DLT) Day 1 to Day 35 All toxicities were graded using the Common Terminology Criteria for Adverse Events version 4.0:
* Grade 1: Mild
* Grade 2: Moderate
* Grade 3: Severe/medically significant but not immediately life-threatening
* Grade 4: Life-threatening
* Grade 5: Death related to adverse event
The occurrence of any of the below was considered a DLT, if judged to be related to talimogene laherparepvec:
* Grade 4 non-hematologic toxicity
* Grade 3 non-hematologic toxicity that lasted \> 3 days despite optimal supportive care
* Any ≥ grade 3 non-hematologic laboratory value if medical intervention was required, the abnormality led to hospitalization or the abnormality persisted for \> 1 week unless deemed not clinically important per both investigator \& sponsor
* Febrile neutropenia grade 3/4
* Thrombocytopenia \< 25 x 10\^9/L associated with bleeding event that required intervention
* Serious herpetic event
* Grade 5 toxicity
* Any intolerable toxicity that led to permanent discontinuation of talimogene laherparepvec
- Secondary Outcome Measures
Name Time Method Overall Response Rate (ORR) Every 12 weeks until the end of follow-up; maximum duration of follow-up was 54.51 months ORR was defined as the percentage of participants who experienced either complete response (CR) or partial response (PR) per modified immune-related response criteria simulating Response Evaluation Criteria in Solid Tumors (irRC-RECIST) response criteria.
CR was defined as the disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment no less than 4 weeks (28 days) from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.
PR was defined as the decrease in tumor burdena ≥ 30% relative to baseline confirmed by a consecutive assessment at least 4 weeks (28 days) after first documentation.Time to Response (TTR) Every 12 weeks until the end of follow-up; maximum duration of follow-up was 54.51 months TTR was defined as the number of days from the first dose of talimogene laherparepvec to the first objective assessment of response as per modified irRC-RECIST.
Duration of Response (DOR) Every 12 weeks until the end of follow-up; maximum duration of follow-up was 54.51 months DOR was defined as the time from the date of an initial response of CR or PR to the earlier of PD/death.
Overall Survival (OS) Every 12 weeks until the end of follow-up; maximum duration of follow-up was 54.51 months OS was defined as as the time from first dose to the event of death from any cause.
OS was estimated using the Kaplan-Meier method.Time to Progression (TTP) Every 12 weeks until the end of follow-up; maximum duration of follow-up was 54.51 months TTP was defined as the time from the first dose of talimogene laherparepvec until objective tumor progression per irRC-RECIST.
TTP was estimated using the Kaplan-Meier method.Progression Free Survival (PFS) Every 12 weeks until the end of follow-up; maximum duration of follow-up was 54.51 months PFS was defined as the time from the first dose to the earlier of disease progression per modified irRC-RECIST or death from any cause.
PFS was estimated using the Kaplan-Meier method.
Trial Locations
- Locations (22)
Centre Hospitalier Universitaire de Marseille - Hopital de la Timone
🇫🇷Marseille cedex 5, France
AI Dupont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Institut Hematologie et Oncologie Pediatrique
🇫🇷Lyon cedex 08, France
Centre Hospitalier Universitaire Sainte Justine
🇨🇦Montreal, Quebec, Canada
Universitaets-Kinderspital
🇨🇭Zuerich, Switzerland
Hospital Sant Joan de Deu
🇪🇸Esplugues de Llobregat, Cataluña, Spain
Institut Curie
🇫🇷Paris, France
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Andalucía, Spain
IRCCS Ospedale Pediatrico Bambino
🇮🇹Roma, Italy
Hospital Universitario Infantil Niño Jesus
🇪🇸Madrid, Spain
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, Comunidad Valenciana, Spain
Universitaets-Kinderspital beider Basel
🇨🇭Basel, Switzerland
Hospital Universitari Vall d Hebron
🇪🇸Barcelona, Cataluña, Spain
Childrens Hospital of Philidelphia
🇺🇸Philadelphia, Pennsylvania, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Cincinnati Childrens Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Ann and Robert H Lurie Childrens Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
Nationwide Childrens Hospital
🇺🇸Columbus, Ohio, United States
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
Nemours du Pont Hospital in Florida
🇺🇸Jacksonville, Florida, United States
Childrens Hospital of Michigan
🇺🇸Detroit, Michigan, United States