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Intrapleural AdV-tk Therapy in Patients With Malignant Pleural Effusion (MpeTK01)

Published: December 13, 2013

Primary Outcome Measures:

Safety [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
The primary study endpoint for the phase I portion is safety based on standard laboratory and clinical adverse event monitoring. Safety profile will be characterized by collection of adverse event information and laboratory values during the treatment phase. Acute toxicity data will be collected at each follow up visit every 2 weeks until week 8. The long term effects will be evaluated at follow up visits very 3 months for 1 year, then every 6 months for the second year. After 2 years, clinical assessment of late toxicity and disease status will be conducted yearly through year 5 after which long-term follow up of general health status will continue yearly through at least 10 years.

Secondary Outcome Measures:

Progression-free survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
Assessed at each visit every 3 months for 1 year, then every 6 months for the second year and then at least yearly until 10 years or until disease progression.
Overall survival [ Time Frame: 10 years ] [ Designated as safety issue: No ]
Follow up for survival for at least 10 years.

Detailed Description:

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.

Three dose levels of AdV-tk will be evaluated. The first two dose levels will receive one injection of AdV-tk through a pleural catheter on day 0. Dose level 3 will receive 2 injections of AdV-tk. Timing for the second administration for dose level 3 will be decided based on the data obtained from dose level 1 and 2. The prodrug, valacyclovir, will be administered orally at a fixed dose for 14 days after each AdV-tk injection. At Level 3, valacyclovir will be administered after the first AdV-tk administration until 14 days after the second administration of AdV-tk.

Chemotherapy may begin at any time after completion of valacyclovir. Choice of chemotherapy depends on the treating oncologist.

Eligibility Criteria

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
  • 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
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