radiation therapy and ammonium tetrathiomolybdate in treating patients with stage i, stage ii, or stage iii non-small cell lung cancer

Conditions: Lung Cancer

Summary: 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.

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.

Eligibility criteria:
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

Keywords: 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