Proton Beam Radiation With Concurrent Chemotherapy and Nelfinavir for Inoperable Stage III Non Small Cell Lung Cancer (NSCLC)
Condition: Non Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Nelfinavir
Intervention description: Two dose levels of Nelfinavir will be evaluated in each concurrent chemotherapy group (carboplatin/paclitaxel and cisplatin/etoposide) at the RPTD does of proton beam radiotherapy: 625 and 1250 mg PO bid.
Intervention MeSH terms: Nelfinavir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Stage IIIA or IIIB NSCLC

Summary:

      Seventy two patients are being asked to take part in this research study because they have
      been diagnosed with Stage IIIA or IIIB non-small cell lung cancer (NSCLC). This study is
      being done to determine the highest safe dose of proton beam radiotherapy and/or study drug
      (called Nelfinavir) that can be given with concurrent chemoradiotherapy to patients with
      cancer without causing bad side effects; and to develop biomarker for clinical outcome. This
      study will be done in two phases. In the first phase, feasibility will be established. We
      will follow patients treatment courses and record side effects at the standard proton
      radiation dose that can be given together with Cisplatinum + Etoposide or Carboplatin +
      Paclitaxel. In the second phase, we will see if it is possible to increase the total proton
      radiation dose or study drug without increasing the number of bad side effects while treated
      together with chemotherapy drugs.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically confirmed diagnosis of NSCLC.

          2. Stage IIIA or IIIB NSCLC.

          3. Patients must have no evidence of metastatic disease based on routine imaging.

          4. Patients must have a Karnofsky Performance Status of 60.

          5. Age 18 and older.

          6. Patients must be able to provide informed consent.

          7. Adequate bone marrow function (i.e. WBC larger than or equal to 4000/mm3, platelets
             larger than or equal to 100,000 mm3).

          8. Adequate renal function for cisplatin or carboplatin as determined by the medical
             oncologist: Usually Calculated creatinine clearance (CrCl) larger than or equal to 45
             mL/min or serum creatinine level smaller than or equal to1.5 x institutional ULN.

          9. Patients must have bilirubin 1.5 mg/dl.

         10. Women of child-bearing potential as long as she agrees to use a recognized method of
             birth control (e.g. oral contraceptive, IUD, condoms or other barrier methods etc).

         11. Hysterectomy or menopause must be clinically documented.

        Exclusion Criteria:

          1. Prior or simultaneous malignancies within the past two years (other than cutaneous
             squamous or basal cell carcinoma or melanoma in situ).

          2. Pregnant women, women planning to become pregnant and women that are nursing.

          3. Actively being treated on any other research study.

          4. For the Nelfinavir phase of the trial only: Patients who are taking Antiarrhythmics
             (amiodarone, quinidine), Antimycobacterial (rifampin), Ergot Derivatives
             (dihydroergotamine, ergonovine, ergotamine, ethylergonovine), Herbal Products (St.
             John's wort/ hypericum perforatum), HMG-CoA Reductase Inhibitors (lovastatin,
             simvastatin), Neuroleptic (pimozide), Proton Pump Inhibitors, or Sedative/ Hypnotics
             (midazolam, triazolam). Note: Patients with the following conditions are deemed
             unsuitable for cisplatin-based chemotherapy (and will be treated with carboplatin):
             (a) Hearing impairment/ peripheral neuropathy Grade 1 or less at baseline (b)
             Symptomatic/uncontrolled congestive heart failure (unable to tolerate volume load with
             pre- and post-cisplatin hydration)