Gemcitabine Hydrochloride and Carboplatin With or Without MK-0646 as First-Line Therapy in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer

This is an interventional treatment trial for Lung Cancer focused on measuring adenosquamous cell lung cancer, squamous cell lung cancer, recurrent non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer Read More

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed squamous cell non-small cell lung cancer (NSCLC)

  • Squamous histology mixed with other NSCLC component (e.g. adenosquamous) allowed

    • No mixed histology with small cell component
• Stage IV disease
• Candidate for palliative chemotherapy

• Measurable disease, defined as ≥ 1 lesion whose longest diameter can be accurately measured as ≥ 2.0 cm by chest X-ray OR as ≥ 1.0 cm by CT scan, CT component of a PET/CT scan, or MRI

  • If the sole site of disease was previously irradiated, there must be evidence of disease progression at that site
• No symptomatic, untreated, or uncontrolled CNS metastases
• Concurrent enrollment on NCCTG-N0392 required

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 12 weeks
• ANC ≥ 1,500/μL
• Platelet count ≥ 100,000/μL
• Hemoglobin ≥ 9 g/dL
• Total bilirubin normal (< 3.0 mg/dL for patients with Gilbert syndrome)
• ALT and AST ≤ 2.5 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 5 times ULN
• Creatinine clearance ≤ 1.2 times ULN OR calculated creatinine clearance ≥ 60 mL/min
• Fasting glucose < 120 mg/dL
• HbA1c ≤ 7%
• INR < 1.5 OR PT/PTT normal (patients receiving anticoagulation therapy with an agent such as warfarin or prophylactic-dose heparin are eligible provided the patient meets the above criteria at the patient's stable dose of anticoagulants)

• QTc < 450 msec and no conduction abnormalities (e.g., heart block) on EKG

  • Isolated premature ventricular or atrial conduction beats allowed
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Willing and able to comply with study
• Willing to return to NCCTG participating center for follow-up
• Willing to provide blood samples as required by study
• Able to complete questionnaire(s) alone or with assistance
• No clinically significant infection
• No significant traumatic injury within the past 4 weeks
• No symptomatic, untreated, or uncontrolled seizure disorder
• No uncontrolled diabetes mellitus, defined as fasting blood glucose ≥ 120 mg/dL on 2 consecutive measurements (taken ≤ 2 weeks apart) or by patient's clinical history

• No other uncontrolled illness including, but not limited to, any of the following:

  • Ongoing or active infection
  • Significant pulmonary symptoms at baseline due to disease
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness/social situation that would limit compliance with study requirements

• No second primary malignancy, except for any of the following:

  • Carcinoma in situ of the cervix
  • Nonmelanomatous skin cancer
  • Other malignancy that was diagnosed and definitively treated ≥ 5 years ago with no subsequent evidence of recurrence
  • History of low-grade (Gleason score ≤ 6) localized prostate cancer, even if diagnosed within the past 5 years
  • Stage I breast cancer that was treated within the past 5 years
• No HIV-positivity and no history of chronic hepatitis B or C (regardless of viral load)
• No evidence or history of bleeding diathesis or coagulopathy

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior chemotherapy for advanced lung cancer, except neoadjuvant therapy, adjuvant therapy, or chemoradiotherapy for lung cancer administered > 12 months ago
• More than 12 months since prior gemcitabine hydrochloride, cisplatin, or carboplatin
• More than 12 months since prior immunotherapy or biologic therapy
• At least 1 week since prior gamma knife radiosurgery for brain metastases or palliative radiotherapy for skeletal metastases and recovered
• At least 2 weeks since prior whole-brain radiotherapy for CNS metastases and recovered
• More than 2 weeks since other prior radiotherapy
• No prior radiotherapy to ≥ 25% of bone marrow
• More than 2 weeks since prior minor surgery*
• More than 4 weeks since prior major surgery (e.g., laparotomy)*
• No other concurrent anticancer drugs or therapy

• No concurrent therapeutic anticoagulation

  • Prophylactic anticoagulation (i.e., low-dose warfarin) of venous or arterial access devices allowed provided the requirements for PT, INR, or PTT are met
• Concurrent radiotherapy for symptom palliation allowed
• Concurrent megestrol acetate for appetite allowed NOTE: *Insertion of a vascular access device is not considered major or minor surgery