Talimogene Laherparepvec in Patients With Unresectable Pancreatic Cancer
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Targeted Delivery of OncoVEX^GM-CSF by Endoscopic Ultrasound (EUS)-Guided Fine Needle Injection (FNI) in Patients With Irresectable Pancreatic Cancer: A Pilot Multinational Experiment on Safety and Proof of Concept|
- Number of Participants With Adverse Events [ Time Frame: From first dose of talimogene laherparepvec until 30 days after the last dose; the median duration of treatment was 44.0 days, 22.0 days, and 11.5 days in each group respectively. ] [ Designated as safety issue: No ]A serious adverse event is defined as any untoward medical occurrence that at any dose results in death, is life threatening, requires hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an important and significant medical event that, based upon appropriate medical judgment, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed above.
- Number of Participants With Talimogene Laherparepvec Detected in Blood and Urine [ Time Frame: Treatment Day 1 predose and 2, 6, 12 and 24 hours postdose, and Week 3 and 6 at (predose and 2 hours postdose. ] [ Designated as safety issue: No ]Samples of blood and urine collected before and up to 24 hours after dosing were tested for the presence of talimogene laherparepvec deoxyribonucleic acid (DNA) using a validated quantitative polymerase chain reaction (qPCR) assay.
- Number of Participants Positive for Anti-herpes Simplex Virus-1 (HSV-1) Antibodies [ Time Frame: Week 0 (Day 1, predose) and Week 3 ] [ Designated as safety issue: No ]Anti-HSV-1 antibodies were detected using an enzyme-linked immunosorbent assay (ELISA).
- Change From Baseline in Sum of Longest Diameters of Injected Tumors [ Time Frame: Baseline and Week 6, 12 and 18 ] [ Designated as safety issue: No ]Spiral computed tomography (CT) scans were performed to assess tumors at screening and at Weeks 6, 12 and 18 after the initial dose.
- Number of Participants With Overall Objective Response [ Time Frame: Every 6 weeks until 12 weeks after the last dose; the median duration of treatment was 44.0 days, 22.0 days, and 11.5 days in each group respectively. ] [ Designated as safety issue: No ]
Tumor response was assessed via CT scan by the investigator using Response Evaluation Criteria In Solid Tumors (RECIST) v1.0 guidelines. Objective response is defined as a complete response (CR) or partial response (PR).
CR: Disappearance of all target and non-target lesions, normalization of tumor marker level and no new lesions and with confirmation no less than 4 weeks after the criteria for CR is first met.
PR: At least a 30% decrease in the sum of longest diameters of target lesions taking as reference the baseline sum of the longest diameters, absence of non-target lesion progression, and no new lesions. These criteria must be confirmed no less than 4 weeks after they are first met.
- Change From Baseline in Pain Intensity [ Time Frame: Baseline and Weeks 3 and 6 ] [ Designated as safety issue: No ]Pain was assessed by the participant using a validated Visual Analog Scale (VAS) pain assessment instrument. A single 10-cm line was used with the leftmost end (0 cm) representing "no pain" and the rightmost end (10 cm) representing "worst pain". The distance was measured from the leftmost part of the scale to the mark made by the participant indicating pain level.
|Study Start Date:||November 2006|
|Study Completion Date:||January 2008|
|Primary Completion Date:||January 2008 (Final data collection date for primary outcome measure)|
Experimental: Talimogene Laherparepvec
Participants received 3 doses of talimogene laherparepvec administered by direct injection 3 weeks apart. At the discretion of the investigator, treatment with talimogene laherparepvec could continue beyond the third dose until week 15 in a regimen of at least 3 weeks between doses.
Biological: Talimogene Laherparepvec
Talimogene laherparepvec administered by direct injection into pancreatic tumors using EUS-guided FNI, up to a maximum of 4 mL per treatment.
Talimogene laherparepvec is a conditionally replication competent herpes simplex type-1 virus designed for use in solid tumors. It has been specifically modified to replicate in tumors and to provide a local source of the immune-stimulating cytokine, granulocyte macrophage colony stimulating factor (GM-CSF). It is injected directly into cancer tumors and is believed to destroy tumor cells by direct infection of the tumor cells and an enhanced immune response due to the release of tumor antigens and GM-CSF expression.
This was an open-label, dose-escalation study evaluating the safety and efficacy of talimogene laherparepvec administered by direct injection into pancreatic tumors using endoscopic ultrasound (EUS)-guided fine needle injection (FNI). Only 1 tumor mass within the body and tail of the pancreas was injected in any participant. The protocol called for evaluation of 4 dosing regimens in sequential cohorts of participants; however, cohort 4 was not opened for enrollment.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00402025
|United States, California|
|UCI Medical Center|
|Orange, California, United States, 92868|
|California Pacific Medical Center|
|San Francisco, California, United States, 94115|
|United States, Texas|
|Mary Crowely Medical Research Center|
|Dallas, Texas, United States, 75246|
|Principal Investigator:||Neil N Senzer, MD||Mary Crowley Medical Research Center|
|Study Director:||Robert Coffin, PhD||BioVex Limited|