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EF5 in Detecting Oxygen Level and Blood Vessels in Tumor Cells of Patients Undergoing Photodynamic Therapy for Intraperitoneal or Pleural Cancer

Not Applicable
Terminated
Conditions
Malignant Ascites
Recurrent Malignant Mesothelioma
Localized Malignant Mesothelioma
Advanced Malignant Mesothelioma
Primary Peritoneal Cavity Cancer
Interventions
Procedure: therapeutic conventional surgery
Other: laboratory biomarker analysis
Registration Number
NCT00028782
Lead Sponsor
National Cancer Institute (NCI)
Brief Summary

This phase II trial is studying how well EF5 works in detecting oxygen level and blood vessels in tumor cells of patients who are undergoing photodynamic therapy for intraperitoneal or pleural cancer. Diagnostic procedures using EF5 to detect oxygen level and blood vessels in tumor cells may help to improve the way photodynamic therapy is given

Detailed Description

OBJECTIVES:

I. Determine the level of hypoxia through etanidazole derivative EF5 binding in patients with intraperitoneal or pleural malignancies treated with photodynamic therapy.

II. Determine the microvascular density in this patient population. III. Determine the relationships between levels of hypoxia, measures of microvascular density, and photosensitizer levels in this patient population.

IV. Correlate hypoxia and photosensitizer levels with clinical outcome in this patient population.

V. Determine the toxic effects of EF5 in this patient population.

OUTLINE: This is a multicenter study.

Patients receive etanidazole derivative EF5 IV over 1-2 hours. Approximately 48 hours after EF5 administration, patients with intraperitoneal tumors undergo surgical resection. Patients with pleural tumors undergo surgical resection approximately 24 hours after EF5 administration. Tumors are then analyzed for EF5 binding and microvascular density by immunohistochemistry and fluorescent antibody techniques.

Patients are followed at 2 weeks and at 30-45 days post EF5 infusion.

PROJECTED ACCRUAL: A total of 80 patients (50 with intraperitoneal malignancy and 30 with pleural malignancy) will be accrued for this study within 2.5 years. Patients are stratified by disease (intraperitoneal malignancy vs pleural malignancy).

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
80
Inclusion Criteria
  • Histologically confirmed intraperitoneal or pleural malignancy

  • Currently enrolled on 1 of 3 photodynamic therapy trials (UPCC-2997, UPCC-4997, or UPCC-05503)

    • Plan to undergo surgery for treatment on one of these protocols
  • Patients with suspected recurrent disease undergoing surgery for diagnosis and debulking allowed if frozen section shows malignant disease

  • No active extra-abdominal metastatic disease and/or intrahepatic involvement secondary to metastatic carcinoma

  • No borderline tumors of low malignant potential

  • No abdominal disease that cannot be debulked to less than 5 mm residual disease in maximal dimension

  • Performance status - ECOG 0-2

  • WBC at least 2,000/mm^3

  • Platelet count greater than 100,000/mm^3

  • Bilirubin less than 1.5 mg/dL

  • No severe liver disease

  • No cirrhosis

  • No grade III or IV elevations in liver function studies

  • Creatinine no greater than upper limit of normal

  • Creatinine clearance at least 60 mL/min

  • Not pregnant or nursing

  • Negative pregnancy test

  • Fertile patients must use effective contraception during and for 1 month after completion of study treatment

  • Weight no more than 130 kg

  • HIV negative

  • Able to tolerate anesthesia or major surgery

  • No grade III or IV peripheral neuropathy

  • No regional enteritis or ulcerative colitis

  • No contraindication for anesthesia or major surgery

  • Prior combination chemotherapy for malignancy allowed

  • No concurrent chemotherapy except for recurrent or persistent disease

  • No concurrent radiotherapy except for recurrent or persistent disease

  • Prior surgery for malignancy allowed

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Diagnostic (etanidazole)etanidazolePatients receive etanidazole derivative EF5 IV over 1-2 hours. Approximately 48 hours after EF5 administration, patients with intraperitoneal tumors undergo surgical resection. Patients with pleural tumors undergo surgical resection approximately 24 hours after EF5 administration. Tumors are then analyzed for EF5 binding and microvascular density by immunohistochemistry and fluorescent antibody techniques.
Diagnostic (etanidazole)therapeutic conventional surgeryPatients receive etanidazole derivative EF5 IV over 1-2 hours. Approximately 48 hours after EF5 administration, patients with intraperitoneal tumors undergo surgical resection. Patients with pleural tumors undergo surgical resection approximately 24 hours after EF5 administration. Tumors are then analyzed for EF5 binding and microvascular density by immunohistochemistry and fluorescent antibody techniques.
Diagnostic (etanidazole)laboratory biomarker analysisPatients receive etanidazole derivative EF5 IV over 1-2 hours. Approximately 48 hours after EF5 administration, patients with intraperitoneal tumors undergo surgical resection. Patients with pleural tumors undergo surgical resection approximately 24 hours after EF5 administration. Tumors are then analyzed for EF5 binding and microvascular density by immunohistochemistry and fluorescent antibody techniques.
Primary Outcome Measures
NameTimeMethod
Levels of microvascular density by PECAM/CD31 stainingAt the completion of surgery

Distributions of the four EF5 binding variables and MVD will be examined graphically we anticipate that certain variables may have a Poisson distribution.

Level of hypoxia in tumor nodulesAt the completion of surgery

Exploratory techniques will be used to describe patterns of EF5 binding as well as MVD within and among patients.

Inter- and intra-patient variability of hypoxia by EF5 bindingAt the completion of surgery

Inter- and intra-subject variability can be estimated using summary statistics (standard deviations, or the range of data).

Associations between hypoxia and photosensitizer levels in tumor nodules with clinical outcome periodically until disease recurrenceNot Provided
Relationships among levels of hypoxia, microvascular density, and photosensitizer levelsAt the completion of surgery
Secondary Outcome Measures
NameTimeMethod
Toxicity of EF5 administrationUp to 45 days after EF5 infusion

All observed toxicities will be graded, tabled for each stratum (IP study) and for the entire study and summarized by frequencies and percentages.

Trial Locations

Locations (1)

Abramson Cancer Center of The University of Pennsylvania

🇺🇸

Philadelphia, Pennsylvania, United States

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