E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
This is a randomized multicenter phase III study. Patient with a high SUVof the primary tumor prior to surgery will be randomised to four cycles of pemetrexed and cisplatin with or without nadroparin for 16 weeks in order to improve the recurrence-free survival rate in these patients. |
|
MedDRA Classification |
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 aim of the study is to investigate whether adding Nadroparin to adjuvant chemotherapy in patients in the poor prognostic group (i.e. high SUV) prolongs recurrence-free survival |
|
E.2.2 | Secondary objectives of the trial |
Secondary end-points are overall survival, dose intensity of subsequent cycles, quality of life, toxicity, health economics. Exploratory endpoints are analysis of blood and tumor samples for prognostic markers, genomics/proteomics. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients with NSCLC, pT2N0, pT1N1, pT2N1, pT3N0 and pT3N1 - SUVmax 7 - Age ≥ 18 years - Patients with NSCLC who had a surgical R0 resection. - WHO Performance score ≤ 2 before chemotherapy. - Adequate organ function before administration of chemotherapy, including: Adequate bone marrow reserve: ANC > 1.5 x 109/L, platelets > 100 x 109/L. Hepatic: bilirubin < 1.5 x ULN, AP, ALT, AST < 3.0 x ULN. Renal: calculated creatinine clearance > 60 ml/min based on the Cockroft and Gault formula. INR < 1.5 - Patients must sign and date a written Independent Ethics Committee approved informed consent form.
|
|
E.4 | Principal exclusion criteria |
- Patients with incomplete or inadequate pulmonary resections. incomplete preoperative or intraoperative staging, wedge or segmental resection. - Prior chemotherapy or radical radiotherapy. - Any unstable systemic disease (including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous year, severe cardiac arrhythmia requiring medication, hepatic, renal or metabolic disease). - Concomitant treatment with any other experimental drug under investigation. - Inability to interrupt aspirin or other nonsteroidal anti-inflammatory agents for a 5-day period (8 day period for long-acting agents such as piroxicam). - Inability or unwillingness to take folic acid, vitamin B-12 supplementation or dexamethasone. - History of any active malignancy (other than NSCLC) unless treated more than 3 years with curative intent and no recurrence, except non-melanoma skin cancer or in situ cervical cancer. - Pregnancy - Men and women of child-bearing potential not using effective means of contraception for 6 months after treatment has been completed - Indication for anticoagulant treatment. - Any contraindication listed in the labeling of nadroparin. - Documented history of heparin-induced thrombocytopenia with UFH or LMWH - Current active bleeding or judged to be as high risk of bleeding. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The main endpoint is recurrence-free survival |
|
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 | No |
E.6.11 | Pharmacogenomic | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
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 |
|
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 | 40 |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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
|
The follow up will continue for 2 years and 3 months further, at the end of which a total of 243 events would be observed allowing the comparison (alpha=0.05 two-sided log-rank test.) of the curves by treatment arm with 80% power to detect a true difference of 60% versus 70% at 3 years, or HR=0.70. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |