Treatment of patients with non-squamous NSCLC, Stage IIIB (with malignant pleural effusion) or Stage IV disease with no prior systemic treatment.
Conditions
Interventions
Product Name: Sagopilone
Product Code: SH Y03757A
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Sagopilone
CAS Number: 305841-29-6
Concentration unit: mg milligram(s)
Conc
Sponsors
Bayer Schering Pharma
Eligibility
Sex/Gender
All
Inclusion criteria
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 (/= 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 ;Secondary Objective: 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 ;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. | — |
Countries
Germany
Outcome results
None listed