A Study of Erlotinib Plus Radiotherapy (RT) for Patients With Advanced or Inoperable Non-Small-Cell Lung Cancer
Condition: Carcinoma, Non-small-cell Lung
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: Erlotinib; Hypofractionated Radiotherapy
Intervention description: Patients will receive Tarceva, 150 mg daily on days -5 through -1 days and will start a course of hypofractionated thoracic RT on Day 1. RT will be administered daily on weekdays (Monday-Friday) and not on weekends or holidays. Tarceva administration will be continued daily during RT (also on weekends/holidays when RT is not given) and after RT will be continued daily as maintenance therapy until death or disease progression.; Patients undergo hypofractionated thoracic RT 5 days a week for approximately 2.5 weeks beginning on day 0. Patients also receive erlotinib hydrochloride PO daily beginning on day -5 and continuing for up to 24 months in the absence of disease progression or unacceptable toxicity.
Intervention MeSH terms: Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Radiation; Erlotinib; Tarceva

Summary:

      It is generally accepted that the presence of chronically hypoxic cells, or tumor cells which
      do not receive enough oxygen as a result of tumor growth, may be an important cause of
      resistance to radiation therapy (RT) and resultant tumor recurrence, particularly in large
      tumors such as advanced non-small-cell lung cancer (NSCLC). Therefore, delivering a higher RT
      dose, as is done with hypofractionated RT, to the tumor may result in higher success rate.

      Erlotinib (Tarceva, previously known as OSI-774) is an orally active, potent, selective
      inhibitor of the Epidermal Growth Factor Receptor (EGFR) tyrosine kinase. A recently
      completed trial has shown that Erlotinib as a single agent significantly improves the
      survival of patients with incurable Stage IIIb/IV NSCLC who have failed standard therapy for
      advanced or metastatic disease. Therefore, Erlotinib is an approved medication for
      second-line therapy in lung cancer following prior chemotherapy.

      This is a Phase II clinical research study to assess the efficacy and toxicity of
      hypofractionated radiation therapy in combination with Erlotinib in patients with locally
      advanced or inoperable non-small-cell lung cancer (NSCLC).

      The investigators' hypothesis is that the addition of erlotinib to RT will result in
      radiosensitization, therefore increasing the likelihood of local tumor control over RT alone.
      Maintenance erlotinib upon RT completion will result in further tumor growth inhibition, both
      systemically and locally, lengthening disease-free survival and overall survival.
    

Eligibility criteria:

        Inclusion Criteria:

        Patients must fulfill all of the following criteria to be eligible for study entry:

          -  Patients aged 18 years or older with histologically or cytologically confirmed
             unresectable or medically inoperable NSCLC and measurable disease.

          -  Patients with AJC Stage IV (metastatic) NSCLC who need initial thoracic RT to control
             symptoms such as hemoptysis, airway obstruction, esophageal compression, superior vena
             cava syndrome, other symptoms, or to prevent symptomatic tumor progression.

          -  Patients with synchronous brain metastases will be allowed to enroll and to receive
             whole-brain radiation therapy while on the protocol.

          -  Patients with unresectable or medically inoperable locally advanced (AJC Stage II,
             IIIA or IIIB) NSCLC, who require thoracic RT but do not qualify for other protocols
             due to the presence of a malignant pleural or pericardial effusion, major weight loss,
             poor performance status, unwillingness to receive chemotherapy or other factors.

          -  Patients with medically inoperable Stage I NSCLC or those patients with a resectable
             Stage I NSCLC who decline surgery.

          -  Patients treated initially with systemic chemotherapy or biologic therapy who
             eventually develop progression of intrathoracic disease and require thoracic RT, or
             who may benefit from consolidative thoracic RT following chemotherapy or biologic
             therapy.

          -  Patients must have a minimal FEV1 of 1.2 l. Lower FEV1 may be allowed for small tumors
             and a V17 <25%.

          -  Estimated life expectancy of 3 months or more.

          -  Patients able to provide a written informed consent prior to study entry.

          -  Patients who agree to have their biopsy or surgical specimen analyzed for the EGFR
             status.

          -  Women of childbearing potential must be willing to practice acceptable methods of
             birth control to prevent pregnancy.

        Exclusion Criteria:

        Any of the following is a criterion for exclusion from the trial:

          -  Small cell lung cancer, any stage

          -  Previous thoracic radiation therapy

          -  Oxygen-dependent patients

          -  FEV1 < 1.2 l

          -  Patients with severe underlying lung disease of any origin, which in the opinion of
             the investigators may markedly increase the risk of treatment-related pneumonitis

          -  Known severe hypersensitivity to Erlotinib or any of the excipients of this product

          -  Concomitant use of phenytoin, carbamazepine, barbiturates, rifampicin, phenobarbital,
             or St John's Wort preparations

          -  Treatment with a nonapproved or investigational drug within 30 days before Day 1 of
             trial treatment

          -  Incomplete healing from previous oncologic or other major surgery

          -  Serum creatinine level greater than CTC grade 2

          -  Pregnancy or breast feeding (women of childbearing potential)