Photodynamic Therapy Using HPPH in Treating Patients With Advanced Non-Small Cell Lung Cancer That Blocks the Air Passages

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Photodynamic therapy uses a drug, such as HPPH, that becomes active when it is exposed to a certain kind of light. When the drug is active, tumor cells are killed. This may be an effective treatment for advanced non-small cell lung cancer that blocks the air passages. PURPOSE: This phase II trial is studying how well photodynamic therapy using HPPH works in treating patients with advanced non-small cell lung cancer that blocks the air passages.

Detailed Description
-----------------
OBJECTIVES: Primary To determine the efficacy of photodynamic therapy (PDT) using HPPH in patients with advanced obstructing endobronchial non-small cell lung cancer. Secondary To determine palliation of symptoms in patients treated with this regimen. To determine the amount of HPPH taken up by the obstructing endobronchial tumors in these patients. To determine the extent of STAT3 cross-links, which are molecular markers of immediate PDT reaction, in the obstructing tumors of these patients before and after PDT treatment. To determine inflammation and apoptosis in the obstructing bronchial tumors of these patients before and after PDT treatment. OUTLINE: Patients receive HPPH IV over 1 hour on day 1. On day 3, patients undergo photodynamic therapy (PDT) comprising laser light delivered by flexible, fiberoptic fibers passed through the biopsy channel of an endoscope. Patients undergo endoscopic debridement on day 5. If viable tumor is found outside of the initial treatment area, patients may receive another dose of laser light without additional HPPH. Patients may undergo tumor biopsies periodically during study for optional biomarker/correlative studies. Tumor tissue samples are analyzed for STAT3 cross-links by western blotting; apoptosis and inflammation biomarkers by immunohistochemistry, TUNEL, and other immunological laboratory methods; and tumor concentrations of HPPH by fluorescence emission spectroscopy. After completion of study treatment, patients are followed at 4-6 weeks and then periodically thereafter.

Official Title
-----------------
A Phase II Study of Photodynamic Therapy (PDT) Using 2-[1-hexyloxyethyl]-2 Devinyl Pyropheophorbide-a (HPPH) for Treatment of Advanced Obstructing Endobronchial Lung Cancer

Conditions
-----------------
Lung Cancer

Intervention / Treatment
-----------------
* Drug: HPPH
* Procedure: endoscopic procedure


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Biopsy confirmed advanced obstructing endobronchial non-small cell lung cancer May have squamous cell carcinoma, adenocarcinoma, or large cell carcinoma histology Ineligible for or refused surgical resection Local endobronchial recurrence after prior surgical resection, radiotherapy, or chemotherapy allowed No evidence of tumor encasement of major pulmonary vessels on CT scan of the chest PATIENT CHARACTERISTICS: Karnofsky performance status (PS) 50-100% OR ECOG PS 0-2 WBC ≥ 4,000/mm³ Platelet count ≥ 100,000/mm³ Prothrombin time < 1.5 times upper limit of normal (ULN) Total bilirubin ≤ 2.0 mg/dL Creatinine ≤ 2.0 mg/dL Alkaline phosphatase (hepatic) ≤ 3 times ULN SGOT ≤ 3 times ULN No contraindications for bronchoscopy Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after the completion of study treatment Patients with underlying lung disease must be judged (by the principal investigator) able to withstand mucous/debris formation at the site of treatment Patients who cannot breathe due to complete upper airway obstruction and who need emergency treatment to open the airway are not eligible No porphyria or hypersensitivity to porphyrin or porphyrin-like compounds No severe chronic obstructive pulmonary disease that, in the opinion of the investigator, would preclude multiple bronchoscopies No partial central airway obstruction from mucous/debris formation No high-grade upper airway obstruction of the trachea PRIOR CONCURRENT THERAPY: Any type of prior therapy (e.g., chemotherapy or radiotherapy) for lung cancer allowed At least 4 weeks since prior and no concurrent chemotherapy or radiotherapy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HPPH<br>Patients will receive 4 mg/m2 HPPH (given light exposure precautions) and approximately 2 days later be treated endoscopically with 150J/cm of 665 +-5nm light. | Drug: HPPH<br>* 4 mg/m2 IV<br>Procedure: endoscopic procedure<br>* Treatment with 150 joules from laser<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Response |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Palliation of Symptoms as Assessed by the Pulmonary Symptom Scale |  | 2 months | 
| Photosensitizer (HPPH) Concentration in Tumor |  | 2 months | 
| STAT3 Cross-links as Assessed by Western Blotting |  | 2 months | 
| Inflammation and Apoptosis as Assessed by Immunohistochemistry |  | 2 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
adenocarcinoma of the lung, large cell lung cancer, squamous cell lung cancer, recurrent non-small cell lung cancer, stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer