Talimogene Laherparepvec In Patients With Unresectable Pancreatic Cancer

Study Overview

Talimogene Laherparepvec in Patients With Unresectable Pancreatic Cancer

The purpose of the study is to assess the safety of injections of talimogene laherparepvec into patients with pancreatic cancer that cannot be removed by surgery. The study will also test whether the injections are effective in treating the tumor.

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.

Pancreatic Cancer

BIOLOGICAL: Talimogene Laherparepvec

005/04

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2006-11-17	Results First Submitted 2015-11-19	Last Update Submitted that met QC Criteria 2016-04-11
First Submitted that Met QC Criteria 2006-11-17	Results First Submitted that Met QC Criteria 2016-04-11	Last Update Posted (ESTIMATED) 2016-04-15
First Posted (ESTIMATED) 2006-11-22	Results First Posted 2016-04-15	Last Verified 2016-04

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
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	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.

Participant Group/Arm

Intervention/Treatment

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

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.

Primary Outcome Measures	Measure Description	Time Frame
Number of Participants With Adverse Events	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.	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.
Number of Participants With Talimogene Laherparepvec Detected in Blood and Urine	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.	Treatment Day 1 predose and 2, 6, 12 and 24 hours postdose, and Week 3 and 6 at (predose and 2 hours postdose.
Number of Participants Positive for Anti-herpes Simplex Virus-1 (HSV-1) Antibodies	Anti-HSV-1 antibodies were detected using an enzyme-linked immunosorbent assay (ELISA).	Week 0 (Day 1, predose) and Week 3

Secondary Outcome Measures	Measure Description	Time Frame
Change From Baseline in Sum of Longest Diameters of Injected Tumors	Spiral computed tomography (CT) scans were performed to assess tumors at screening and at Weeks 6, 12 and 18 after the initial dose.	Baseline and Week 6, 12 and 18
Number of Participants With Overall Objective Response	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.	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.
Change From Baseline in Pain Intensity	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.	Baseline and Weeks 3 and 6

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

cytological or histological proof of adenocarcinoma of the pancreas
unresectable, locally advanced disease (isolated liver metastases are permitted)
tumors of at least 1 cm diameter at screening
measurable disease using Response Evaluation Criteria In Solid Tumors (RECIST) criteria
failure of either standard therapy, OR any one of the following:

no alternative therapeutic of higher curative potential is available;
investigator determination that patient could not tolerate alternative therapeutic due to unacceptable toxicity; or,
patient refusal to be treated with available alternative therapeutic
age > 18 years
life expectancy > 3 months
adequate bone marrow function as indicated by:

White blood cells (WBC) ≥ 3.0 x 10^9/L
platelets ≥ 100 x 10^9/L
hemoglobin ≥ 8.5 gm/dL
adequate liver function as indicated by:

bilirubin < 1.5 x upper limit of normal (ULN)
alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 5 x ULN in case of presence of liver metastasis
ALT or AST < 2.5 x ULN in case of absence of liver metastasis
adequate renal function as indicated by a serum creatinine level < 1.5 x ULN.
adequate hemostasis indicated by international normalized ratio (INR) ≤ 1.5
mentally, physically and geographically able to undergo treatment and follow-up
provided written informed consent
first patient in each cohort only: seropositive for herpes simplex virus type 1 (HSV1)

history of other malignancy within two years prior to screening, except for prostate cancer (T1c, T2ab with definitive treatment, prostate-specific antigen (PSA) < 1 ng/ml, and without ongoing hormone suppression) or adequately treated in situ carcinoma of the cervix, basal cell carcinoma, or squamous cell carcinoma of the skin
cystic form of pancreatic cancer; microcystic disease may be eligible upon discussion with Medical Monitor
Common Terminology Criteria for Adverse Events (CTCAE) version 3 grade 2 or greater clinical pancreatitis within 8 weeks prior to dosing with OncoVEX^GM-CSF
other than metastases limited to the liver, imaging evidence of metastatic disease to any other organ or tissue
any serious concomitant systemic disorder that would compromise the safety of the patient, at the discretion of the investigator
evidence of compromised immune function including but not limited to:

clinically significant absolute lymphocyte count < Lower Limit of Normal (LLN)
known human immunodeficiency virus (HIV), acute or chronic active hepatitis B, or hepatitis C infection;
concurrently taking HIV antiviral medications (e.g. protease inhibitors, azidothymidine, etc.)
received intravenous (IV), intramuscular (IM) or subcutaneous (SC) human gamma globulin within 6 months prior to dosing with OncoVEX^GM-CSF
patients taking immunosuppressive agents (e.g. cyclosporine, tacrolimus, or oral or systemic corticosteroids at a dose of > 10 mg/day of prednisone or equivalent).
pregnancy, lactation or lack of effective contraception in women of child-bearing potential (e.g., not post menopausal for > 2 years, or had tubal ligation); lack of effective contraception in men if the partner is of child-bearing potential; women must have been practicing an effective contraceptive method for at least three months prior to entry in to the trial (hormonal contraception or intrauterine device in conjunction with a barrier method); men must use a condom or be surgically sterilized
patients with active bacterial or viral infections that require treatment with systemic antibiotics or antiviral agents within 2 weeks prior to the first dose of OncoVEX^GM-CSF); (note: patients with active cold sores or other HSV1 infections must wait until those lesions have crusted over before receiving OncoVEX^GM-CSF)
surgery requiring general or spinal anesthesia within four weeks prior to dosing with OncoVEX^GM-CSF
Treatment with an investigational agent within 4 weeks prior to the first dose of OncoVEX^GM-CSF
serum carbohydrate antigen (CA)19.9 levels > 3000 U/mL at screening
evidence of ascites on screening abdominal computed tomography (CT) scan

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Neil N Senzer, MD, Mary Crowley Medical Research Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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Resources

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Caregivers

Clinical Trial Record