E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with unresectable stage IIIA and IIIB Non small cell lung cancer (NSCLC) without bone metastases |
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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 objective of the study is to evaluate the efficacy of Zometa in delaying disease progression or recurrence or death in patients with locally advanced, stage IIIA and IIIB NSCLC. The primary endpoint is progression free survival. Patients in the treatment arm will receive Zometa every 3-4 weeks. Patients in the control arm will not receive Zometa treatment until development of bone metastases. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives include evaluation of: • Time to occurence of bone metastases • Rate of bone metastases (irrespective whether symptomatic or not ) at 6, 12, 18 and 24 months • Time to disease progression (TTP), censoring non-cancer deaths • Risk of skeletal related events (SREs) at 12 and 24 months from study entry based on multiple event analysis by the Anderson-Gill method and rate of SRE at 12 and 24 months (proportion of patients having experienced at least one SRE) • Time to first SRE • Survival at 12 and 24 months •Time to occurrence of bone metastases in the subgroup of high risk patients (high risk assessed by BSP expression in the primary tumor). • Rate of bone metastases (irrespective whether symptomatic or not) at 6, 12, 18 and 24 months in the subgroup of high risk patients (high risk assessed by BSP expression in the primary tumor).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age ≥ 18 years • Histologically or cytologically confirmed NSCLC(squamous cell carcinoma, adenocarcinoma, large cell carcinoma) NOTE: Mixed tumors with small cell carcinoma and aplastic carcinoma are not eligible • Stage IIIA and Stage IIIB at diagnosis excluding patients with pleural effusion at the time of randomisation • Patients must hve received the primary treatment for their disease and no progression should have occured •Life expectancy of at least 6 months • ECOG performance status of 0 or 1 • Weight loss ≤ 10% in the 6 months before diagnosis of NSCLC • Women of childbearing potential must use a medically acceptable form of contraception during the study and must have a negative urine or serum pregnancy test within 7 days of randomisation. • Adequate bone marrow reserve defined as white blood cell (WBC) ≥ 3500mm3, neutrophils ≥ 1500 mm3, platelets ≥ 100,000 mm3, Hb ≥ 9 g/dL • Able and willing to sign informed consent •Patients must have recovered from previous thoracotomy
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E.4 | Principal exclusion criteria |
• Patients with NSCLC with pleural effusion at the time of randomisation • Patients who received any prior bisphosphonates in past 12 months • Presence of metastasis • Patients with current malignancy within past 5 years other than NSCLC (exceptions include treated melanoma, ductal carcinoma in situ of the cervix or other cancer cured by resection alone) • Thoracotomy ≤ 3 weeks prior to randomization •More than 8 months from the start of the primary antitumour treatment • Patients with abnormal renal function as evidenced by a calculated creatine clearance < 30ml/minute • Current active dental problems including infection of the teech or jawbone (maximilla or mandibular); dental or fixed trauma, or a current or prior diagnosis of osteonecrosis of the jaw (ONJ), of exposed bone in the mouth, or of slow healing after dental procedures • Recent (within 6 weeks) or planned dental or jaw surgery (e.g. extraction, implants) • Corrected serum calcium < 8.0 mg/dL • Known hypersensitivity to Zometa or other bisphosphonates • Patients with nonmalignant conditions which would confound the evaluation of the primary endpoint, impair tolerance of therapy, or prevent compliance to the protocol, including: - Uncontrolled infections - Uncontrolled Type 2 Diabetes Mellitus - Diseases with influence on bone metabolism such as Paget’s disease or uncontrolled thyroid or parathyroid dysfunction - Cardiovascular, renal, hepatic, pulmonary and neurologic/psychiatric diseases which would prevent prolonged follow-up • Patients who, in the opinion of the investigator, are unlikely to cooperate fully during the study •Patients in whom the primary antitumor treatment is still ongoing
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of the study is to evaluate the efficacy of Zometa in the prevention of bone metastases in patients with locally advanced, stage IIIA and IIIB NSCLC. The primary endpoint is time to occurrence of bone metastases. All patients in both arms will receive standard antineoplastic treatment at the discretion of their physicians. Patients in the treatment arm will receive Zometa every 3-4 weeks. The patients in the control arm will not receive Zometa treatment until development of bone metastases. |
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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 | Yes |
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 | 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) | 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 | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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 | No |
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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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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All possible efforts must be made to determine the reason(s) why a patient fails to return for scheduled visits or is discontinued from the trial. If either study treatment or observations were discontinued for any patient, the reason will be recorded. Patients withdrawn during the trial will not be replaced. Patients who discontinue the study early should still complete an end of treatment assessment four weeks after the last dose. |
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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 | |
E.8.9.1 | In the Member State concerned months | 24 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 24 |