Chemotherapy With or Without Porfimer Sodium-Based Photodynamic Therapy During Surgery in Treating Patients With Malignant Pleural Mesothelioma

Status: Active

Description

This randomized phase II trial studies how well chemotherapy with or without porfimer sodium-based photodynamic therapy during surgery works in treating patients with malignant pleural mesothelioma. Drugs used in chemotherapy, such as pemetrexed disodium, work in different ways to stop the growth of cancer, either by killing the cancer cells, by stopping them from dividing, or by stopping them from spreading. Photodynamic therapy uses a drug, such as porfimer sodium, that becomes active when it is exposed to a certain kind of light. When the drug is active, tumor cells are killed. It is not yet known whether chemotherapy is more effective with or without porfimer sodium-based photodynamic therapy during surgery in treating patients with malignant pleural mesothelioma.

Eligibility Criteria

Inclusion Criteria

  • Patients with a histologic diagnosis of malignant pleural mesothelioma (MPM), epithelioid subtype, who in the opinion of the attending thoracic surgeon can receive a macroscopically complete resection of tumor
  • Patients must have disease limited to the hemithorax
  • Patients who have received prior surgery, gene therapy, or combination chemotherapy will be permitted if it has been at least 30 days since the last treatment
  • Subjects treated with pemetrexed (pemetrexed disodium) previously will be eligible only if 8 weeks have elapsed between the last dose of pemetrexed and the date of surgery
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Medical suitability for resection, including documented medical and cardiac clearance
  • Patients must sign a document that indicates that they are aware of the investigative nature of the treatment of this protocol, and the potential benefits and risks; patients unwilling or unable due to cognitive impairment to sign informed consent are excluded from the study

Exclusion Criteria

  • Patients with active invasive cancers, other than MPM, that require additional treatment, except non-melanomatous skin cancer, superficial bladder or cervical cancer, and early-stage prostate cancer
  • Pregnant or lactating patients
  • Patients who have a history of human immunodeficiency virus (HIV) disease
  • Patients who have a white blood cell count less than 2,500 per cubic mm
  • Platelets less than 100,000/cubic mm
  • Serum creatinine equal or greater than 2.5 mg/deciliter
  • Patients who have severe liver disease including cirrhosis, grade III-IV elevations in liver function studies, or bilirubin in excess of 1.5 mg/deciliter
  • Patients with porphyria or hypersensitivity to porphyrin or porphyrin-like compounds
  • Patients who have been treated with pemetrexed if the last dose of pemetrexed is < 8 weeks to the date of surgery
  • Patients that have been treated with prior mantle field radiation
  • Patients with distant metastatic disease or otherwise not confined to the ipsilateral hemithorax

Locations & Contacts

New York

Buffalo
Roswell Park Cancer Institute
Status: Active
Contact: Todd L. Demmy
Phone: 877-275-7724
Email: todd.demmy@roswellpark.org

Pennsylvania

Philadelphia
University of Pennsylvania / Abramson Cancer Center
Status: Active
Contact: Keith A. Cengel
Phone: 215-906-2183
Email: cengel@mail.med.upenn.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To test the superiority of overall survival (OS) in mesothelioma patients who undergo radical pleurectomy (RP) plus photodynamic therapy (PDT) relative to that of patients who undergo RP.

SECONDARY OBJECTIVES:

I. To determine whether the addition of PDT to surgery and postoperative chemotherapy improves progression free survival (PFS).

II. To assess serum for cytokine, tumor-associated antigen and anti-tumor antibody levels before and after surgery or surgery/PDT.

III. To evaluate molecular and microenvironment markers by immunohistochemical studies of excised tissue.

IV. To assess the contribution of toxicity from the photodynamic therapy. (For PDT subjects only)

V. To measure the uptake of Photofrin (porfimer sodium) in normal and malignant tissue. (For PDT subjects only)

VI. To evaluate activation of cytokine and growth factor signaling in tissue specimens obtained before, during and after surgery or surgery/PDT. (For PDT subjects only)

VII. To make non-invasive optical measurements of tumor and normal tissues, including optical properties, tissue oxygenation, photosensitizer uptake, and blood flow. (For PDT subjects only)

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive porfimer sodium intravenously (IV) over 5-15 minutes. Approximately 24 hours later, patients undergo RP with intraoperative PDT. Within 4-8 weeks after surgery, patients receive up to 4 courses of pemetrexed disodium with a platinum agent or other suitable regimen at the discretion of the study medical oncologist.

ARM II: Patients undergo RP. Within 4-8 weeks after surgery, patients receive pemetrexed disodium with a platinum agent or other suitable regimen at the discretion of the study medical oncologist as in Arm I.

After completion of study treatment, patients are followed up at 1 month, every 3 months for 24 months, and then every 3-6 months for up to 10 years.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
University of Pennsylvania / Abramson Cancer Center

Principal Investigator
Keith A. Cengel

Trial IDs

Primary ID UPCC 14513
Secondary IDs NCI-2014-01242, 819186, UPCC # 14513
Clinicaltrials.gov ID NCT02153229