This study is a prospective, randomized, double-blind, multi-center placebo-controlled phase II study in order to determine progression-free survival of patients with platinum-resistant or refractory ovarian carcinoma treated with topotecan plus sorafenib versus topotecan plus placebo.
Conditions
Interventions
Trade Name: Nexavar
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Sorafenib
Current Sponsor code: BAY 43-9006
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration
Sponsors
Charité - Universitätsmedizin Berlin
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with histologically confirmed epithelial ovarian cancer, primary peritoneal carcinomatosis or fallopian tube cancer 2. Patients must have platinum resistant (relapse-free interval =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. History of cardiac disease: congestive heart failure >NYHA class 2; active coronary artery disease (CAD) or myocardial infarction within the past 6 months (MI more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled arterial hypertension with systolic blood pressure >160 mmHg or diastolic blood pressure > 90 mm Hg despite optimal treatment 2. Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 5 years prior to study entry 3. Prior radiological or clinical evidence of CNS metastases including previously treated, resected, or asymptomatic brain lesions or leptomeningeal involvement by head CT scan or MRI 4. Known or suspected hypersensitivity reaction to topotecan or any ingredient of topotecan or sorafenib or any ingredient of sorafenib 5. Active clinically serious infections (> grade 2 NCI-CTC version 3.0) 6. History of HIV infection or chronic hepatitis B or C 7. History of organ allograft 8. Patients with history of colon perforation 9. Patients with history of colitis or neutropenia colitis 10. Patients with evidence or history of bleeding diathesis 11. Serious non healing wound, fracture or ulcer 12. Patients undergoing renal dialysis 13. Patients unable to swallow oral medications 14. Significant disease which, in the investigator’s opinion, would exclude the patient from the study 15. Substance abuse, medical, psychological or social conditions that may interfere with the patient’s participation in the study or evaluation of the study results 16. Patients with seizure disorder requiring medication (such as steroids or anti-epileptics) 17. Medical or psychological conditions that would not permit the subject to complete the study or sign informed consent 18. Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study 19. Legal incapacity or limited legal capacity 20. Participation in another clinical study with experimental therapy within the 30 days before start of treatment 21. Subjects housed in an institution on official or legal orders 22. Patients with prior therapy containing topotecan 23. Patients with prior therapy containing Avastin or other VEGFR TK1 24. Any other anticancer chemotherapy or immunotherapy or investiagitional drug therapy outside of this trial during the study or within 4 weeks prior to study entry. 25. Radiotherapy during study or within 4 weeks prior to start of study drug and prior radiotherapy of > 25% of the bone marrow (exception: palliative radiotherapy of non-target lesions or pain therapy or local bone irradiation) 26. Autologous bone marrow transplant or stem cell rescue within 4 months of study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determination of the progression-free survival (PFS) of patients treated with topotecan + sorafenib versus topotecan + placebo;Secondary Objective: • Overall survival • Response rate • Duration of response • Time to progression (TTP) • Safety and tolerability • Assessment of quality of life over time as defined by EORTC-QLQ C 30 and Ovar 28 questionnaire and, in case of participation in the sub-study, FOSI, respectively • Translational research within the Tumor bank Ovarian cancer Network (www.toc-network.de) • Development of a prognostic index (GCIG Symptom Benefit Group) ;Primary end point(s): The primary endpoint is the determination of the progression-free survival (PFS) of patients treated with topotecan + sorafenib versus topotecan + placebo. | — |
Countries
Germany
Outcome results
None listed