OncoVEX GM-CSF in Patients With Unresectable Pancreatic Cancer

This study has been completed.
Sponsor:
Information provided by:
BioVex Limited
ClinicalTrials.gov Identifier:
NCT00402025
First received: November 17, 2006
Last updated: August 10, 2011
Last verified: August 2011
  Purpose

The purpose of the study is to assess the safety of injections of OncoVEX GM-CSF 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.


Condition Intervention Phase
Pancreatic Cancer
Genetic: OncoVEX GM-CSF modified herpes-simplex 1 virus
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
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

Resource links provided by NLM:


Further study details as provided by BioVex Limited:

Primary Outcome Measures:
  • Adverse event summaries of events, changes in vital signs, blood chemistry and hematology captured prior to and following treatment to end of study [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Tumor response assessed via CT scan using RECIST [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
  • Effects on pain relief using a patient self-assessment pain scale [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: November 2006
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Genetic: OncoVEX GM-CSF modified herpes-simplex 1 virus
    multiple dose levels, every 3 weeks for up to 6 injections
    Other Name: OncoVex gm-csf
Detailed Description:

The outcome for most patients with pancreatic cancer is very poor. Surgery offers the only change for cure. Unfortunately, at the time of diagnosis, 80 to 90% of patients have inoperable or metastatic disease. Chemotherapy (Gemcitabine) and chemoradiation therapy offer only a small therapeutic effect and primarily affect pain and overall condition. Given the poor prognosis of pancreatic cancer, many alternative strategies have been tested to improve treatment results. A wide variety of gene and immunotherapies have been tested.

OncoVEX GM-CSF 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, GM-CSF. It 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.

OncoVEX GM-CSF will be delivered directly to pancreatic tumors using EUS-FNI. A series of three injections will be administered of 6 weeks. Patients will be hospitalized for the first injection. Screening will occur within 3 weeks of the first injection and visits for injections will occur at 0, 3 and 6 weeks. Spiral CT scans of chest and abdomen will be done prior to each injection and again at 12 weeks (6 weeks after last injection)and also at 18 weeks if response has occurred. Assessments of pain, vital signs and laboratory evaluations will occur at each visit. If appropriate patients may be offered up to three additional injections.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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:

    • WBC ≥ 3.0 x 109/L
    • platelets ≥ 100 x 109/L
    • hemoglobin ≥ 8.5 gm/dL
  • adequate liver function as indicated by:

    • bilirubin < 1.5 x upper limit of normal (ULN)
    • ALT or 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 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 HSV1

Exclusion Criteria:

  • history of other malignancy within two years prior to screening, except for prostate cancer (T1c, T2ab with definitive treatment, 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
  • CTCAE v3 grade 2 or greater clinical pancreatitis within 8 weeks prior to dosing with OncoVEXGM 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 HIV, acute or chronic active hepatitis B, or hepatitis C infection;
    • concurrently taking HIV antiviral medications (e.g. protease inhibitors, AZT, etc.)
  • received IV, IM or SC human gamma globulin within 6 months prior to dosing with OncoVEXGM CSF
  • patients taking immunosuppressive agents (e.g. cyclosporine, tacrolimus, or oral or systemic corticosteroids at a dose of >10mg/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 OncoVEXGM-CSF); (note: patients with active cold sores or other HSV1 infections must wait until those lesions have crusted over before receiving OncoVEXGM-CSF)
  • surgery requiring general or spinal anesthesia within four weeks prior to dosing with OncoVEXGM CSF
  • Treatment with an investigational agent within 4 weeks prior to the first dose of OncoVEXGM CSF
  • serum CA19.9 levels > 3000 U/mL at screening
  • evidence of ascites on screening abdominal CT scan
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00402025

Locations
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
Sponsors and Collaborators
BioVex Limited
Investigators
Principal Investigator: Neil N Senzer, MD Mary Crowley Medical Research Center
Study Director: Robert Coffin, PhD BioVex Limited
  More Information

No publications provided

Responsible Party: Robert Coffin, PhD, BioVex Inc
ClinicalTrials.gov Identifier: NCT00402025     History of Changes
Other Study ID Numbers: OncoVEX GM-CSF 005/04
Study First Received: November 17, 2006
Last Updated: August 10, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by BioVex Limited:
Metastatic
Pancreas
Adenocarcinoma

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on September 30, 2014