Intrapleural AdV-tk Therapy in Patients With Malignant Pleural Effusion

Study Overview
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Brief Summary
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This is a phase I study of intrapleural AdV-tk therapy in patients with malignant pleural effusion (MPE). The primary objective is to test the safety of intrapleural AdV-tk therapy. Secondary objectives are to evaluate clinical efficacy and biologic activity

Detailed Description
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The goal of this open-label, dose escalation clinical trial is to investigate if the administration of AdV-tk to patients with MPE followed by valacyclovir and chemotherapy is safe, can be effectively delivered without disturbing standard therapy, and will have anti-tumor activity in patients with solid tumors. The first and second dose levels have been completed, and the study is currently expanded to enroll more patients to dose level 2 with Celecoxib. Patients will receive one injection of AdV-tk through a pleural catheter on day 0. The prodrug, valacyclovir, will be administered orally at a fixed dose for 14 days after each AdV-tk injection. Celecoxib will be administered starting 3 days before AdV-tk and continuing for 2 days after AdV-tk administration. Chemotherapy may begin at any time after completion of valacyclovir. Choice of chemotherapy depends on the treating oncologist.

Official Title
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A Phase I Study of Intrapleural AdV-tk Therapy in Patients With Malignant Pleural Effusion

Conditions
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Lung Cancer, Malignant Pleural Effusion, Mesothelioma, Breast Cancer, Ovarian Cancer

Intervention / Treatment
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* Biological: AdV-tk + valacyclovir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have MPE (defined as positive pleural fluid cytology). Eligible patients include NSCLC, small cell lung cancer, malignant mesothelioma (MM), breast cancer and ovarian cancer. Diagnosis must be made prior to AdV-tk injection. For patients with MM, histologic proof is needed, but positive pleural fluid cytology is not required. Patients must have an indication for placement of pleural catheter Patients must be 18 years of age or older Performance status must be ECOG 0-1 Acute toxic effects from any prior radiotherapy, chemotherapy, or prior surgical procedures must have resolved to NCI CTCAE v 4.0 grade ≤ 1 Baseline pulmonary function tests must be FEV1 ≥1 liter or 40% of predicted value (may be post-drainage and/or bronchodilator) Bilirubin ≤ 1.5 x upper limit of normal (ULN) and ALT, AST and alkaline phosphatase ≤ 2 x ULN Serum creatinine < 2 mg/dl and calculated creatinine clearance > 30 ml/min Hemoglobin ≥ 9 g/dL, ANC > 1000/mm3 and platelets > 100,000/mm3 Serum albumin level ≥ 2.5 g/dL Patients must give study specific informed consent prior to enrollment Exclusion Criteria: Patients may not be on systemic corticosteroids (>10 mg prednisone per day) or other systemic immunosuppressive drugs Patient is not known to be HIV+ Patient is not pregnant or breast-feeding. Female patients of childbearing age must have negative serum or urine pregnancy test within 1 week of beginning therapy. Patient may not have clinically significant pericardial effusion Patient may not have other serious co-morbid illness or compromised organ function Patient may not have liver disease including known cirrhosis, active hepatitis or chronic active hepatitis B No prior allergic reaction or hypersensitivity to sulfonamides, celecoxib, aspirin or other NSAIDs No concurrent use of other NSAID or aspirin exceeding 100mg/day during celecoxib administration. No wash-out period required.

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: Study Arm<br>AdV-tk + valacyclovir | Biological: AdV-tk + valacyclovir<br>* AdV-tk will be administered intrapleural through pleural catheter followed by oral valacyclovir. Valacyclovir will be administered orally at a fixed dose for 14 days after each AdV-tk administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment emergent adverse events |  | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | 5 years | 
| Overall survival |  | 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunotherapy, Gene therapy, Tumor vaccine