Gene Transfer for Cancer Pain

Study Overview
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Brief Summary
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The primary purpose of this study is to examine the safety of NP2 (a nonreplicating HSV-based vector expressing enkephalin) in patients with cancer pain. The secondary purpose is to evaluate efficacy.

Detailed Description
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Therapeutic HSV-based vectors deliver genes from skin inoculation to sensory neurons to interrupt pain signaling at the spinal level. Side effects may be limited by the focal distribution of vector delivery and preproenkephalin expression. Preproenkephalin is a natural human gene that produces peptides that bind to opioid receptors in the body. The therapeutic being evaluated, NP2, is a replication defective herpes simplex type 1 virus (HSV-1) modified to express the human preproenkephalin gene that has demonstrated efficacy in numerous model of pain, including pain caused by cancer.

Official Title
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Gene Transfer for Intractable Pain: A Phase I Clinical Trial to Determine the Maximum Tolerable Dose of a Replication-Defective Herpes Simplex Virus Type I (HSV-1) Vector Expressing Human Preproenkephalin (NP2) in Patients With Malignancies

Conditions
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Cancer Pain

Intervention / Treatment
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* Biological: NP2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with intractable pain from malignant disease with a 5 year projected survival of less than 25%. Female patients of childbearing potential who have a negative pregnancy test and using birth control. Patients who have not received recent treatment with a radiation, chemotherapeutic or immunotherapeutic agent and are not expected to undergo such treatment 28 days after injection of NP2. Patients who have not had surgical stabilization/resection within 4 weeks of Screening and have no plans for additional surgical procedures. Patients with adequate bone marrow function, IgG levels greater than 565 mg% and CD4 count greater than 500. . Exclusion Criteria: Patients with serious uncontrolled medical conditions other than malignancy. Patients with severe liver or renal impairment Patients currently or previously with positive serology for HIV, Hepatitis B or Hepatitis C. Patients with a hemoglobin <9 gm% or uncontrolled coagulopathy or bleeding diathesis. Patients with a clinical diagnosis of any active herpes infection within the past 6 months. Patients who have been vaccinated to prevent HSV infection or a history of shingles or the presence of active shingles.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NP2<br>Intradermal injection | Biological: NP2<br>* Intradermal injection of NP2 at doses ranging from 10e7 to 10e9 pfu at the site of pain.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety measured by vital signs, physical exam findings, clinical laboratory analyses and treatment related Adverse Events (AE). |  | 4 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate changes in cancer-related pain |  | 4 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gene therapy, replication defective HSV vector, pain, enkephalin, intradermal