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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2015 by Advantagene, Inc.
Sponsor:
Collaborator:
University of Pennsylvania
Information provided by (Responsible Party):
Advantagene, Inc.
ClinicalTrials.gov Identifier:
NCT01997190
First received: November 19, 2013
Last updated: April 13, 2015
Last verified: April 2015
  Purpose

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


Condition Intervention Phase
Malignant Pleural Effusion
Lung Cancer
Mesothelioma
Breast Cancer
Ovarian Cancer
Biological: AdV-tk + valacyclovir
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Intrapleural AdV-tk Therapy in Patients With Malignant Pleural Effusion

Resource links provided by NLM:


Further study details as provided by Advantagene, Inc.:

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 2-3 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.


Estimated Enrollment: 19
Study Start Date: October 2013
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Study Arm
AdV-tk + valacyclovir
Biological: AdV-tk + valacyclovir
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.

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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • 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.
  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: NCT01997190

Locations
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadephia, Pennsylvania, United States, 19104
Contact: Susan Metzger    215-615-5478    Susan.Metzger@uphs.upenn.edu   
Principal Investigator: Charu Aggarwal, MD         
Sponsors and Collaborators
Advantagene, Inc.
University of Pennsylvania
Investigators
Principal Investigator: Charu Aggarwal, MD University of Pennsylvania
  More Information

No publications provided

Responsible Party: Advantagene, Inc.
ClinicalTrials.gov Identifier: NCT01997190     History of Changes
Other Study ID Numbers: MpeTK01
Study First Received: November 19, 2013
Last Updated: April 13, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Advantagene, Inc.:
Immunotherapy
Gene therapy
Tumor vaccine

Additional relevant MeSH terms:
Pleural Effusion
Pleural Effusion, Malignant
Mesothelioma
Adenoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms, Mesothelial
Pleural Diseases
Pleural Neoplasms
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Valacyclovir
Anti-Infective Agents
Antiviral Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on September 02, 2015