E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of patients with non-squamous NSCLC, Stage IIIB (with malignant pleural effusion) or Stage IV disease with no prior systemic treatment. |
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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 establish the maximum tolerated dose (or the recommended phase II dose) and the preliminary tolerability profile of Sagopilone when used in combination with a fixed dose of carboplatin and bevacizumab in previously untreated patients with stage IIIB/IV non-squamous NSCLC
Phase II part •To investigate the efficacy of Sagopilone in combination with carboplatin and bevacizumab in previously untreated patients with stage IIIB/IV non-squamous NSCLC using the Sagopilone dose determined in part I
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E.2.2 | Secondary objectives of the trial |
Phase I part •To investigate the pharmacokinetics of Sagopilone and carboplatin when given in combination with bevacizumab
Phase II part • To evaluate the safety and tolerability of the combination of Sagopilone plus carboplatin and bevacizumab
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Supplemental study of gene regulation in patients with non-small-cell lung cancer who participate in Study 311135 of Sagopilone in combination with carboplatin and bevacizumab. 2008-04-16 Final version incl. in the main protocol. |
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E.3 | Principal inclusion criteria |
1. Males or females aged >/= 18 years 2. Histologically or cytologically proven NSCLC, Stage IIIB (with cytologically confirmed malignant pleural effusion) or Stage IV disease 3. At least one unidimensionally measurable lesion (suitable for modRECIST evaluation) 4. WHO performance status 0 to 1
5. Adequate function of major organs and systems • Hematopoietic: - Hemoglobin: >/= 10 g/dL - WBC: >/= 3,000/mm3 - Absolute neutrophil count: >/= 1,500/mm3 - Platelet count: >/= 100,000/mm3 - Coagulation: PT, PTT within normal limits. • Hepatic: - - Total bilirubin: within normal range (</= 1.5 times the upper limit of normal in case of liver metastases) - AST/ALT: </= 3 times the upper limit of normal (</= 5 times the upper limit of normal in case of liver metastases) • Renal: - - Creatinine: </= 2 mg/dL 6. Survival expectation >/= 3 months
7. Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment
8. Agreement to use highly effective contraception methods (intra-uterine contraceptive device IUCD, condoms, oral contraceptives, or other adequate barrier contraception) in females of child-bearing potential and adequate barrier birth control measures in men during the course of the trial and two weeks after the completion of the trial.
9. Ability to understand and the willingness to sign a written informed consent. A signed informed consent form must be obtained prior to any study specific procedures.
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E.4 | Principal exclusion criteria |
1. Squamous or predominantly squamous cell histology of NSCLC 2. Any prior systemic treatment for NSCLC 3. Radiotherapy within 3 weeks prior to study entry 4. Candidacy for curative resection 5. Brain metastases (cranial CT/MRI is required) 6. History of GI perforation and/or internal organ fistula 7. Previous or concurrent cancer that is distinct in primary site or histology from the NSCLC evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1], or any cancer curatively treated less than 3 years before study entry. 8. Hemoptysis (> 2.5 ml of red blood) within 6 months prior to study entry 9. Any other hemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks prior to study entry. 10. Congenital bleeding diathesis, acquired coagulopathy or patients receiving full dose of anticoagulants for the treatment of thromboembolism. Low-dose acetyl salicylic acid is permitted 11. History of cardiac disease: congestive heart failure >NYHA class 2. Patients must not have unstable angina (anginal symptoms at rest) or new-onset angina (that began within the last 3 months) or myocardial infarction within the past 6 months
12. Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mm Hg, despite optimal medical management 13. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy 14. Known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C 15. Proteinuria (urine protein more than 1+ [i.e. by dipstick or urinanalysis] or more than 1g protein in 24 hr urine) 16. Clinically active serious infections (> grade 2 NCI-CTCAE version 3.0) 17. Breast feeding 18. Hypersensitivity to the active substance or to any of the excipients of any of the study medications 19. Hypersensitivity to Chinese hamster ovary (CHO) cell products or other recombinant human or humanized antibodies. 20. Any condition that in the opinion of the investigator could hamper the compliance with the study protocol. 21. Use of any investigational drug within 4 weeks before start of the study regimen or inadequate recovery from any toxic effects of such therapy. 22. Serious, non-healing wound, ulcer, or bone fracture 23. Patients undergoing renal dialysis 24. Thrombotic or embolic events such as cerebrovascular accident including transient ischemic attacks within the past 6 months 25. Any of the following previous and concomitant therapies and medications: • Major surgery open biopsy or significant traumatic injury within 4 weeks of start of study • Autologous bone marrow transplant or stem cell rescue within 4 months of study • Use of biologic response modifiers, such as G-CSF, within 3 week of study entry (see section 6) 26. Peripheral neuropathy of CTCAE grade 2 or higher 27. Uncontrolled concurrent illness 28. Central tumor location or cavitation of tumors
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase I: In the Phase I part of this study the primary efficacy variable will be the maximum tolerated dose (MTD) or recommended phase II dose (RPIID). Phase II: In the Phase II part of the study the primary efficacy variable will be the best overall response rate (BOR). The BOR will be assessed according to the modified RECIST criteria. |
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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 | Yes |
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) | Information not present in EudraCT |
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 | Yes |
E.7.1.3.1 | Other trial type description |
DLT and MTD of Sagopilone in combination |
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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 | 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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 10 |