E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10041071 |
E.1.2 | Term | Small cell lung cancer stage unspecified |
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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 |
This Phase III trial is designed to compare the efficacy and safety of picoplatin plus best supportive care (BSC) with BSC alone as second-line therapy for patients with small cell lung cancer (SCLC) who have disease that is refractory to initial chemotherapy or progressive within 6 months of completing first-line, platinum-containing chemotherapy. |
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E.2.2 | Secondary objectives of the trial |
The secondary efficacy endpoints will be 1) the proportion of subjects who achieve an objective response (complete response + partial response); 2) the proportion of subjects who achieve disease control (complete response + partial response + stable disease); 3) duration of response; 4) progression-free survival (PFS). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histological or cytological diagnosis of SCLC or combined SCLC/non-small cell lung cancer (NSCLC) defined as SCLC mixed with squamous cell carcinoma, adenocarcinoma, or large cell carcinoma. 2. One and only 1 prior cisplatin or carboplatin-containing chemotherapy regimen for SCLC within the scope of the National Comprehensive Cancer Network (NCCN) Guidelines (Section 5.4.1). 3. Radiological evidence of SCLC that never responded or progressed within 90 days after completion of first-line therapy (refractory); or responded initially to first-line therapy but progressed between 91 and 180 days after treatment was completed (progressed within 91 to 180 days). 4. CT scans of chest and entire abdomen (including adrenals and full extent of liver) with contrast, preferably within 14 days prior to randomization (up to 21 days is allowed if necessary). MRI is acceptable in the case of allergy to contrast agents. The presence or absence of measurable disease by RECIST must be documented from the baseline CT or MRI scan. 5. Head CT or MRI scan within 14 days prior to randomization (up to 21 days is allowed if necessary) demonstrating absence of brain metastases. 6. ECOG PS 0, 1 or 2 within 3 days prior to randomization (Appendix II). 7. Life expectancy of at least 8 weeks within 3 days prior to randomization. 8. At least 21 days must have elapsed since the most recent prior chemotherapy dose (42 days for nitrosoureas), with evidence of hematological recovery. 9. At least 14 days must have elapsed since the most recent prior radiotherapy dose. 10. At least 14 days must have elapsed since prior surgery except for the placement of venous access device or bronchoscopy. 11. Subject must be recovered to ≤ Grade 1 toxicity from all non-hematological adverse effects of prior therapies (excluding alopecia). 12. Age 18 years or over. 13. ANC ≥ 1.5 x 109/L. 14. Platelet count ≥ 100 x 109/L. 15. Hemoglobin of ≥ 90 g/L (transfusion permitted to achieve this hemoglobin). 16. Aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase levels ≤ 2.5 times upper limit of normal (ULN) or ≤ 5 times ULN if liver involvement is present. 17. Bilirubin of ≤ 1.5 times upper limit of normal (ULN). 18. Blood urea nitrogen ≤ 1.5 times ULN (hypovolemic subjects may be hydrated to achieve this BUN). 19. Creatinine clearance of ≥ 50 mL/min, as calculated by the Cockcroft-Gault formula (Appendix III). 20. Women of childbearing potential must have a negative pregnancy test (serum or urine). Sexually active couples of child-bearing potential must agree to use appropriate birth control methods during chemotherapy and for 3 months after chemotherapy. 21. Signed informed consent. |
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E.4 | Principal exclusion criteria |
1. Prior radiotherapy that included ≥ 30% of the bone marrow (Appendix IV). 2. Pleural effusion as the only radiological evidence of SCLC. 3. Brain or central nervous system (CNS) metastases. 4. Grade 2 or higher peripheral neuropathy. 5. Significant cardiac disease, defined as myocardial infarction within 3 months prior to randomization, congestive heart failure classified by the New York Heart Association as Class III or IV (Appendix V), uncontrolled cardiac arrhythmias, poorly controlled or unstable angina, or electrocardiographic evidence of acute ischemia. 6. Serious medical or psychiatric illness that could potentially interfere with the completion of study treatment according to this protocol, e.g., active infection, Crohn’s disease, ulcerative colitis, etc. 7. Use of other investigational drugs within 30 days prior to randomization. 8. Breast-feeding. 9. History of any other malignancy within 5 years, with the exception of treated non-melanoma skin cancer or carcinoma in situ of the cervix. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall survival – the interval from the date of randomization to the date of death from any cause. |
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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 | 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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | 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 |
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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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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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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 | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |