E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary nonsquamous non-small cell lung cancer (NSCLC) stage IIIb/IV with wild-type KRAS |
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E.1.1.1 | Medical condition in easily understood language |
Lung cancer which is either locally extended or has developed metastasis and is of a special type |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025054 |
E.1.2 | Term | Lung cancer non-small cell stage IIIB |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029522 |
E.1.2 | Term | Non-small cell lung cancer stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029521 |
E.1.2 | Term | Non-small cell lung cancer stage IIIB |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025055 |
E.1.2 | Term | Lung cancer non-small cell stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to estimate the efficacy of the combination consisting of cisplatin/pemetrexed and panitumumab in patients with wild-type KRAS (non-mutated status) in terms of progression-free survival rate at 6 months. |
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E.2.2 | Secondary objectives of the trial |
- Determination of the tumour response - Duration of response - Overall survival - Adverse effects / toxicity - Quality of life assessment
Additionally, genetic analyses of tumor tissue and blood samples are performed to identify predictive markers. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival rate after 6 months |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Determination of the tumour response 2. Duration of response 3. Overall survival 4. Adverse effects / toxicity 5. Quality of life assessment |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. At 12 weeks (end of chemotherapy treatment) 2. At end of Follow-Up (2 years) 3. At end of Follow-Up (2 years) 4. At end of Follow-Up (2 years) 5. At end of Follow-Up (2 years) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Standard treatment with pemtrexed and cisplatin |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 20 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Cf. section 5.11 of the protocol |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |