Carcinoma, Non-Small-Cell Lung
Conditions
Keywords
NSCLC, Stage IIIb or IV, Nonsquamous, KRAS-Wildtype
Brief summary
The purpose of this trial is to estimate the therapeutic efficacy of the experimental targeted regimen including the EGFR antibody panitumumab (in combination with pemetrexed and cisplatin) in relation to the standard combination in patients with a KRAS wild-type stage IIIB or IV primary nonsquamous non-small cell lung cancer. It is expected that the progression free survival rate at 6 months is improved by the targeted regimen.
Interventions
DRUGPanitumumab
Panitumumab 9 mg/kg BW will be administered IV every 3 weeks (q3w) for a maximum of four cycles. In case of CR, PR or SD status at the end of the combination treatment, a panitumumab single drug treatment, consisting of 9 mg/kg BW administered every 3 weeks, will be performed until detection of disease progression.
DRUGPemetrexed
Pemetrexed 500 mg/m² will be administered IV every 3 weeks (q3w) for a maximum of four cycles.
DRUGCisplatin
Cisplatin 75 mg/m² will be administered IV every 3 weeks (q3w) for a maximum of four cycles.
Sponsors
Gesellschaft fur Medizinische Innovation - Hamatologie und Onkologie mbH
WiSP Wissenschaftlicher Service Pharma GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression free survival rate at 6 months | 6 months |
Secondary
| Measure | Time frame |
|---|---|
| Adverse effects / toxicity | 6 months |
| Quality of life assessment | 6 months |
| Determination of the tumour response | 6 months |
| Duration of response | 6 months |
| Overall survival | 6 month |
Countries
Germany
Outcome results
None listed