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

This study is currently recruiting participants.
Verified November 2013 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: November 22, 2013
Last verified: November 2013
  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 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 Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Study Arm
AdV-tk administered intrapleural through pleural catheter followed by oral valacyclovir.
Biological: AdV-tk + valacyclovir
Three dose levels of AdV-tk will be evaluated. 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.

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

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
  • 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
  Contacts and Locations
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: November 22, 2013
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Breast Neoplasms
Lung Neoplasms
Mesothelioma
Ovarian Neoplasms
Pleural Effusion
Pleural Effusion, Malignant
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Mesothelial
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Pleural Diseases
Pleural Neoplasms
Valacyclovir
Antiviral Agents

ClinicalTrials.gov processed this record on April 17, 2014