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

Sponsor

Candel Therapeutics, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01997190

Collaborator

University of Pennsylvania (Other)

Enrollment

Location

Arm

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Malignant Pleural Effusion Lung Cancer Mesothelioma Breast Cancer Ovarian Cancer	Biological: AdV-tk + valacyclovir	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

19 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2013

Actual Primary Completion Date :

Dec 1, 2015

Actual Study Completion Date :

Feb 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
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.

Arm

Intervention/Treatment

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.

Outcome Measures

Primary Outcome Measures

Safety [8 weeks]
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 [5 years]
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 [10 years]
Follow up for survival for at least 10 years.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.