E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Extensive disease (ED) stage small-cell lung cancer (SCLC) |
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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 |
Phase I-part: To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of ZK 219477 in combination with cisplatin
To investigate the safety and tolerability of ZK 219477 in combination with cisplatin
Phase II-part: To evaluate the anti-tumor activity of ZK 219477 in combination with cisplatin in patients with chemotherapy-naive, extensive-disease stage small cell lung cancer
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E.2.2 | Secondary objectives of the trial |
Phase I-part: To investigate the pharmacokinetics of ZK 2194777 and cisplatin when given as a combination
To evaluate the anti-tumor activity of ZK 219477 in combination with cisplatin in patients with chemotherapy-naive, extensive-disease stage small cell lung cancer
Phase II-part: To investigate the safety and tolerability of ZK 219477 in combination with cisplatin in this patient population
To evaluate the population pharmacokinetics of ZK 219477 and cisplatin |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Patients must meet the following criteria to enroll in this study:
1. Males or females aged > 18 years
2. Histologically or cytologically proven SCLC
3. Stage of extensive disease defined by the presence of distant metastases
4. At least 1 unidimensionally measurable lesion (suitable for modRECIST evaluation)
5. WHO performance status 0 to 1
6. Adequate function of major organs and systems
• Hematopoietic: - Hemoglobin >10 g/dL - WBC:> 3.0 x 109/L - Absolute neutrophil count: >1.5 x 109/L - Platelet count: >100 x 109/L
• Hepatic: - Total bilirubin: within normal range (< 1.5 times the upper limit of normal in case of liver metastases) - AST/ALT:< 2.5 times the upper limit of normal (< 5 times the upper limit of normal in case of liver metastases)
• Renal: - Creatinine: <1.5 times the upper limit of normal - Creatinine clearance: > 60 ml/min
• Cardiovascular:No symptomatic congestive heart failure - No unstable angina pectoris - No myocardial infarction < 6 months prior to randomization - No arrhythmia needing continuous treatment
• Nervous system: - No Grade 2 or greater peripheral neuropathy
• Ear: - No Grade 2 or greater hearing impairment
• No other uncontrolled concurrent illness
• No active infection
7. Survival expectation of at least three months
8. Negative pregnancy test at enrollment (females of childbearing potential only)
9. Agreement to use a highly effective method of birth control for adults of reproductive potential
10. Written informed consent
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E.4 | Principal exclusion criteria |
Patients must not be enrolled if they meet any of the following criteria:
1. Prior chemotherapy for SCLC
2. Prior surgical resection for SCLC within 4 weeks prior to inclusion. Patient must have recovered from all therapy related toxicities.
3. Prior radiotherapy for SCLC with the exception of radiation of brain metastases. At least 3 weeks must have elapsed since radiotherapy and patient must have recovered from all therapy related toxicities; the site of previous radiotherapy should have evidence of progressive disease if it is the only site of disease.
4. Superior vena cava syndrome or obstruction of any vital structure
5. Untreated malignant hypercalcemia
6. Extensive disease amenable to radiation therapy
7. Symptomatic brain metastases requiring whole-brain irradiation (please note: patients with brain metastases not requiring whole brain irradiation can be enrolled)
8. History of another primary malignancy within the last 5 years with the exceptions of non-melanoma skin cancer and carcinoma in situ of the cervix
9. Known allergy or hypersensitivity to platinum-containing drugs
10. Pregnant or breast-feeding women
11. Any condition that in the opinion of the investigator could hamper the compliance with the study protocol
12. Use of any investigational drug within 4 weeks before start of study treatment or inadequate recovery from any toxic effects of such therapy
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients with either complete response (CR) or partial response (PR) as "best overall response" |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
MTD and DLT of ZK 219477 in combination with cisplatin |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
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 | 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
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |