Gated Intensity Modulated Radiation Therapy and Concurrent Chemotherapy for Inoperable NSCLC

A Phase I Dose Intensification Study Using Gated Intensity Modulated Radiation Therapy and Concurrent Chemotherapy for Patients With Inoperable, Non-Small Cell Lung Cancer

Radiation therapy technology that allows increased radiation dose to the tumor while sparing healthy tissue will improve the balance between complications and cure.

The primary objective is to establish the maximum tolerated fractional dose (MTfD) of radiotherapy to a total dose of 78Gy using gated IMRT, delivered in single daily fractions that can be administered concurrently with Taxol® and carboplatin chemotherapy. Secondary objectives include: to evaluate the toxicity of concurrent Taxol® and carboplatin with gated IMRT; identify partial organ tolerance doses for lung and esophagus when treating with involved field thoracic 3D; estimate complete response rate as defined by PET performed 3 months after completion of all therapy.

Inclusion Criteria:

• Patients with histologically-proven, by biopsy or cytology, unresectable lung cancer of the following histologic types: squamous cell carcinoma, adenocarcinoma, large cell carcinoma, non-small cell carcinoma, not otherwise specified.
• Patient with AJCC Stage IIIA-IIIB, if all detectable tumor can be encompassed by radiation therapy fields, including both the primary tumor and the involved regional lymph nodes.
• 18-fluoro-2-deoxyglucose positron emission tomography required for staging and image fusion for treatment planning.
• Atelectasis, if present, must be less than one lung.
• Patients must have granulocytes >1500/µl; platelets >100,000/µl; bilirubin < 1.5 mg/dl; AST(SGOT) < 2 ULN; serum creatinine < 2.0 mg/dl.
• Zubrod Score 0-1.
• FEV1 must be >1.0 L.
• Patients must sign a study-specific informed consent form prior to study entry
• Patients must have measurable disease on the planning CT.
• Patient must have a completed the IMRT plan and the attending physician must have reviewed and approved the dose volume histograms as follows (based on treatment planning to the Phase 4 dose level): total lung V20 < 30%, mean esophageal dose < 34 Gy, the esophageal V55 < 30%, the heart V40 < 50%.
• No prior or concurrent malignancy except non-melanomatous skin cancer unless disease-free for one year or more; no prior lung cancer within last two years.
• No prior RT to thorax.
• No previous chemotherapy or previous biologic response modifiers for current lung cancer or within the past five (5) years.
• No distant metastases or supraclavicular lymph node involvement or significant atelectasis.
• No clinically significant pleural effusions, pericardial effusions or superior vena cava syndrome.

Exclusion Criteria:

• Undifferentiated small cell (oat cell or high grade neuroendocrine) carcinoma, any stage.
• Stage I, II or IV NSCLC.
• Complete tumor resection, recurrent disease, or those patients eligible for definitive surgery.
• Concurrent malignancy except non-melanomatous skin cancer or prior cancer unless disease-free for one year or more.
• Prior radiation therapy to the thorax.
• Previous chemotherapy or previous biologic response modifiers for current lung cancer or within the past five (5) years.
• Distant metastases or supraclavicular lymph node involvement, or atelectasis of an entire lung.
• Patients who have not had the pre-treatment evaluations in Section 4.0 or evaluations performed > 8 weeks prior to study entry.
• Patients with clinically significant pleural effusions, pericardial effusions or superior vena cava syndrome.
• Prior lung cancer within the last two years.
• Patients who have significant atelectasis and in whom the CT definition of the gross tumor volume(GTV) is difficult to determine.
• Pregnant or lactating females. It is not known what effects this treatment may have on the developing fetus.