Talimogene Laherparepvec in Patients With Unresectable Pancreatic Cancer

• ClinicalTrials.gov Identifier: NCT00402025
• Recruitment Status: Completed
• First Posted: November 22, 2006
• Results First Posted: April 15, 2016
• Last Update Posted: April 15, 2016
• Sponsor: BioVex Limited
• Information provided by (Responsible Party): BioVex Limited

Tracking Information

• First Submitted Date: November 17, 2006
• First Posted Date: November 22, 2006
• Results First Submitted Date: November 19, 2015
• Results First Posted Date: April 15, 2016
• Last Update Posted Date: April 15, 2016
• Study Start Date: November 2006
• Actual Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 11, 2016)

• 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. ]
  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. ]
  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 ]
  Anti-HSV-1 antibodies were detected using an enzyme-linked immunosorbent assay (ELISA).

Original Primary Outcome Measures (submitted: November 17, 2006)

• Adverse event summaries of events captured prior to and following treatment to end of study
• Effects on hematology, biochemistry as changes from values obtained prior to treatment and summaries of clinically significant abnormalities
• Effects on vital signs

Current Secondary Outcome Measures (submitted: April 11, 2016)

• Change From Baseline in Sum of Longest Diameters of Injected Tumors [ Time Frame: Baseline and Week 6, 12 and 18 ]
  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. ]
  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 ]
  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.

Original Secondary Outcome Measures (submitted: November 17, 2006)

• Tumor response assessed via CT scan using RECIST
• Survival time assessed from first injection of OncoVEX
• Effects on pain relief using a patient self-assessment pain scale

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Talimogene Laherparepvec in Patients With Unresectable Pancreatic Cancer
• 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
• Brief Summary: 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.

Detailed Description

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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Pancreatic Cancer

Intervention

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.

Other Names:

• OncoVEX^GM-CSF
• T-VEC
• IMLYGIC

Study Arms

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.

Intervention: Biological: Talimogene Laherparepvec

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 11, 2016): 17
• Original Enrollment (submitted: November 17, 2006): 15
• Actual Study Completion Date: January 2008
• Actual Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 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)

Exclusion Criteria:

• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00402025
• Other Study ID Numbers: 005/04
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: BioVex Limited
• Study Sponsor: BioVex Limited
• Collaborators: Not Provided

Investigators

• Principal Investigator: Neil N Senzer, MD; Mary Crowley Medical Research Center
• Study Director: Robert Coffin, PhD; BioVex Limited

• PRS Account: BioVex Limited
• Verification Date: April 2016