Panitumumab Plus Pemetrexed and Cisplatin (PemCisP) Versus PemCis in the First-line Treatment of Patients With Non-small Cell Lung Cancer

Inclusion Criteria:

• Histologically confirmed diagnosis of inoperable stage IIIB or IV primary pulmonary nonsquamous NSCLC (according to UICC staging valid until 2008)
• Sufficient representative sample material for KRAS analysis
• Wild-type KRAS
• Informed consent of the patient
• Aged at least 18 years
• WHO Performance Status 0-2
• At least one unidimensional, measurable tumour parameter according to RECIST
• Life expectancy of al least 12 weeks

• Adequate haematological, hepatic, renal and metabolic function parameters:

  • Leukocytes > 3000/mm³, ANC ≥ 1500/mm3, platelets ≥ 100,000/mm3, Creatinine clearance ≥ 50 ml/min and serum creatinine ≤ 1.5 x upper limit of normal
  • Bilirubin ≤ 1.5 x upper limit of normal, GOT-GPT ≤ 2.5 x upper limit of normal in absence of liver metastases, or ≤ 5 x upper limit of normal in presence of liver metastases, AP ≤ 5 x upper limit of normal
  • Magnesium ≥ lower limit of normal; calcium ≥ lower limit of normal

Exclusion Criteria:

• Prior chemotherapy
• Clinically manifest, uncontrolled brain metastases
• Prior radiotherapy of the parameters to be measured
• Peripheral neuropathy NCI grade > 1
• Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment.
• Subject (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment (adequate: oral contraceptives, intrauterine device or barrier method in conjunction with spermicidal jelly).
• Serious concurrent diseases.
• Major surgery within the last 4 weeks before recruitment
• On-treatment participation in a clinical study in the period 30 days prior to inclusion.
• Clinically significant cardiovascular disease in (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before enrolment.
• Ongoing or active infection, including active tuberculosis or known infection with human immunodeficiency virus.
• Superior vena cava syndrome contraindicating hydration.
• History of interstitial lung disease, e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan.
• Patient with mild to moderate renal insufficiency who are unable to interrupt salicylates (like aspirin) or other nonsteroidal anti-inflammatory drugs (NSAIDS) for a 5-day period starting 2 days before administration of pemetrexed (8-day period for long-acting agents such as piroxicam). Exception: Low dose aspirin (acetyl salicylic acid) intake up to 150 mg per day is permitted without interruption.
• Presence of clinically significant third-space fluid collections, for example, ascites or pleural effusions that cannot be controlled by drainage or other procedures
• Inability or unwillingness to take folic acid, vitamin B12 supplementation or dexamethasone (or equivalent corticosteroid); or any other inability to comply with protocol or study related procedures
• Prior or concurrent malignancy (≤ 5 years prior to enrolment in study) except non-melanoma skin cancer or cervical carcinoma FIGO stage 0-1 if the patient is continuously disease-free
• Known allergic reactions on study medication