Locally Advanced NSCLC Hyperfractionated RT
Condition: Carcinoma, Non Small Cell Lung (NSCLC)
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: Carboplatin; Paclitaxel; Daily hyperfractionated radiation therapy
Intervention description: Single arm non randomized open label study. Subjects will receive standard of care Carboplatin IV once a week. Chemotherapy is given concurrently with daily hyperfractioned radiation therapy.; Single arm non randomized open label study. Subjects will receive standard of care Paclitaxel IV once a week. Chemotherapy is given concurrently with daily hyperfractioned radiation therapy.; All subjects will receive 6 fractions(2Gy per fraction) of radiation therapy weekly. All subjects will complete an interim PET-CT after 48Gy-54Gy of RT . Subjects with a complete response on PET will complete RT at 60 Gy; subjects who have residual disease on interim PET and meet strict planning constraints eligibility will proceed to boost RT for a total RT dose of 72Gy. Interim PET-CT response will be measured using PERCIST criteria.
Intervention MeSH terms: Paclitaxel; Carboplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a prospective phase II study designed to evaluate an accelerated and adaptive RT
      approach for locally-advanced non-small cell lung cancer (NSCLC). All eligible subjects will
      have an interim PET-CT during radiation therapy to determine the metabolic complete response
      rate. Radiation therapy will be given in an accelerated fashion (2 Gy/fraction, 6
      fractions/week) with concurrent chemotherapy. Interim responses will be assessed using
      PERCIST criteria.

      Despite concurrent chemotherapy and radiation therapy, local/regional failure occurs in ~50%
      of patients with locally-advanced NSCLC. Clinical studies have demonstrated that accelerated
      fractionation (giving the same total dose in a shorter period of time) improves outcomes in
      several malignancies, including lung cancer. Administering higher than conventional doses of
      RT to all sites of original disease leads to inferior outcomes. Adapting the RT approach,
      giving a higher dose to slowly responding disease as assessed with interim PET has been shown
      to be feasible. PERCIST (Positron Emission Tomography Response Criteria in Solid Tumors)
      provides guidelines on how to report responses to therapy based on PET-CT. PET-CT response
      has been shown to be prognostic in a variety of clinical scenarios in lung cancer including
      after induction therapy. In one study, PET was performed after neoadjuvant chemoradiotherapy
      (40-50.4 Gy). Complete or partial metabolic response using PERCIST criteria was predictive of
      loco-regional, distant, and overall progression-free survival.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologic/cytologic documentation of non-small cell lung cancer (NSCLC)

          2. Unresectable stage II, IIIA, or IIIB disease

          3. Zubrod/ECOG performance status 0-1

          4. Weight loss < 10% in preceding 3 months prior to diagnosis

          5. Adequate organ function defined as the following

          6. Absolute neutrophil count of ≥ 1,500 and platelet count ≥ 100,000

          7. Cockcroft calculated creatinine clearance of ≥ 45 ml/min or 1.5 x the upper limit of
             normal (ULN)

          8. A total bilirubin ≤ 1.5 ULN, aspartate aminotransferase (AST) ≤ 2.0 x ULN

          9. ≥ 18 years of age.

         10. Negative pregnancy test in women of child-bearing potential

         11. Signed study-specific informed consent.

         12. No prior chemotherapy or radiotherapy for NSCLC

         13. No prior mediastinal or thoracic radiation

        Exclusion Criteria:

          1. Prior thoracic irradiation.

          2. Medical contraindications to thoracic irradiation.

          3. Pre-existing sensory neuropathy of grade ≥ 2

          4. Pleural effusion: when pleural fluid is visible on both CT scan and on a chest x-ray,
             a pleuracentesis is required to confirm that the pleural fluid is cytologically
             negative.

             Patients with effusions that are minimal (i.e. not visible on chest x-ray) or that are
             too small to safely tap are eligible

          5. Patients with contralateral hilar involvement