Radiation Therapy and Ammonium Tetrathiomolybdate in Treating Patients With Stage I, Stage II, or Stage III Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Ammonium tetrathiomolybdate may stop the growth of non-small cell lung cancer by blocking blood flow to the tumor. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving ammonium tetrathiomolybdate together with radiation therapy may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects of giving radiation therapy together with ammonium tetrathiomolybdate in treating patients with stage I, stage II, or stage III non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary To assess the acute toxicity of combining antiangiogenic copper reduction with ammonium tetrathiomolybdate (TM) and standard external-beam radiotherapy in patients with stage I-IIIB non-small cell lung cancer. Secondary To measure changes in biological markers of angiogenesis (i.e., ELISA analysis of serum bFGF, VEGF, TGF-beta, IL-6, and IL-8) affected by TM or radiotherapy and an imaging technique (technetium 99m sestamibi) known to correlate with intratumoral angiogenesis. To follow the late toxicity that exists when angiogenic inhibition with the copper reduction agent TM is combined with standard external-beam radiotherapy in these patients. To collect tumor response, recurrence rate, and survival data on these patients. OUTLINE: Induction phase: Patients receive oral ammonium tetrathiomolybdate (TM) 4 times daily for up to 3 weeks. Radiotherapy: Patients undergo radiotherapy once daily, 5 days a week, for 6-7 weeks along with concurrent TM. Maintenance phase: Patients continue to receive TM for a total of 1 year . Blood is collected periodically for analysis of laboratory outcomes by ELISA and technetium 99m sestamibi scans. Biomarkers may include VEGF, bFGF, TGF-beta, interleukin (IL)-6, and IL-8. After completion of study therapy, patients are followed every 3 months for up to 2 years.

Official Title
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The Combination of Radiotherapy With the Anti-Angiogenic Agent Tetrathiomolybdate (TM) in the Treatment of Stage I-IIIB Non-Small Cell Lung Cancer (NSCLC): A Phase I Study

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: ammonium tetrathiomolybdate
* Other: immunoenzyme technique
* Other: laboratory biomarker analysis
* Radiation: Tc 99m sestamibi
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) meeting the following criteria: Squamous, large cell undifferentiated, or adenocarcinoma Sputum cytology not acceptable evidence of cell type Cytologic specimens obtained by brushing, washing, or needle aspiration of a defined lesion allowed Stage I-IIIB disease No evidence of distant metastases Planning to receive definitive radiotherapy alone or post-operative radiotherapy (for gross residual disease or positive margin) Medically inoperable disease or chemotherapy or surgery refused Mediastinal lymph nodes must be evaluated by either mediastinoscopy or by PET scan, unless definitive CT-positive mediastinal disease is noted If patient cannot tolerate mediastinoscopy and no PET is available, the technetium 99m sestamibi scan is allowed for assessment of the mediastinum No stage IIIB disease with pleural effusions or stage IV disease No small cell lung cancer or mixed small cell/non-small cell histology PATIENT CHARACTERISTICS: SWOG performance status 0-2 Hemoglobin ≥ 9.0 g/dL WBC ≥ 3,000/mm³ ANC ≥ 1,200/mm³ Platelet count ≥ 80,000/mm³ Creatinine < 1.8 mg/dL Prior malignancy allowed if disease free for ≥ 5 years Nonmelanoma skin cancer allowed within 5 years Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No grade 3 hemoptysis (or hemoptysis not requiring transfusion, but where the radiation oncologist has concerns about a 3-week delay in treatment) No pneumonia due to bronchial obstruction (or a high-grade bronchial obstruction where the radiation oncologist has concerns about a 3-week delay in treatment) No transfusion dependence requiring > 2 units of packed RBCs every 2 weeks for more than 28 days No medically serious acute or chronic medical condition that is unstable and/or requires intensive management PRIOR CONCURRENT THERAPY: See Disease Characteristics Prior thoracic radiation allowed if the new lesion can be treated with absolutely no overlap of previous treatment fields At least 3 weeks since prior surgery No concurrent chemotherapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: ammonium tetrathiomolybdate|4 times daily for up to 3 weeks|
|Other: immunoenzyme technique|nan|
|Other: laboratory biomarker analysis|nan|
|Radiation: Tc 99m sestamibi|nan|
|Radiation: radiation therapy|once daily, 5 days a week, for 6-7 weeks|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute toxicity |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of markers of angiogenesis in serum (VEGF, bFGF, TGF-beta, IL-6, IL-8) |  |  | 
| Assessment of markers of angiogenesis on imaging (technetium 99m sestamibi) scans |  |  | 
| Late toxicity |  |  | 
| Collection of response, recurrence, and survival data |  | every 3 months for up to 2 years | 

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