This study is a prospective single-arm, open-label, multicenter phase I/II trial. The phase I-trial is a dose-escalation trial to determine the maxium tolerated dose (MTD) of pazopanib in combination with weekly topotean. The phase II-trial is a single arm open-label trial to further assess the safety and the efficacy of this combination of treatment. MedDRA version: 19.0 Level: LLT Classification code 10033131 Term: Ovarian carcinoma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Hycamtin 1 mg
Product Name: Hycamtin
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: TOPOTECAN
CAS Number: 123948-87-8
Concentration unit: mg milligram(s)
Concen
Sponsors
Charité - Universitätsmedizin Berlin
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients must provide written informed consent prior to performance of study specific procedures or assessments, and must be willing to comply with treatment and follow up assessments and procedures. 2. Histologically confirmed diagnosis of epithelian ovarian cancer, primary peritoneal carcinoma or fallopian tube cancer. 3. Patients must have platinum resistant (recurrence within 6 months of a platinum-containing regimen) or platinum refractory (progression during platinum treatment) or intermediate platinum-sensitive (recurrence within 12 months after a platinum-based primary therapy) disease. 4. No more than 2 prior treatment regimens for epithelial ovarian cancer 5. Age ³18 years 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 7. Adequate organ function defined as in the table below. 8. There must be measurable disease or evaluable disease according to RECIST criteria. 9. Able to swallow and retain oral medication. 10. A life expectancy of at least 12 weeks. 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 48 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 11. Prior malignancies; subject who have had another malignancy and have been disease-free for 5 years which effect progression free survival, or subject with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible 12. History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug. Screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastases. 13. Clinically significant gastrointestinal abnormalities that might interfere with oral dosing or that may increase the risk for gastrointestinal bleeding including, but not limited to: Active peptic ulcer disease Known intraluminal metastatic lesion/s with suspected bleeding Inflammatory bowel disease (e.g. ulcerative colitis, Crohn’s disease), or other gastrointestinal conditions with increased risk of perforation History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment 14. Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to: Malabsorption syndrome Major resection of the stomach or small bowel 15. Grade 3 or 4 diarrhoea 16. Any unstable or serious concurrent condition (e.g., active infection requiring systemic therapy). 17. Poorly controlled hypertension [defined as systolic blood pressure (SBP) of =140 mmHg or diastolic blood pressure (DBP) of = 90mmHg]. Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. BP must be re-assessed on two occasions that are separated by a minimum of 1 hour; on each of these occasions, the mean (of 3 readings) SBP / DBP values from each BP assessment must be 480 msecs using Bazett’s formula. 19. History of any one or more of the following cardiovascular conditions within the past 6 months: Cardiac angioplasty or stenting Myocardial infarction Unstable angina Symptomatic peripheral vascular disease Coronary artery by-pass graft surgery 20. Class III or IV congestive heart failure as defined by the New York Heart Association (NYHA) 21. History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulant agents (excluding therapeutic warfarin) for at least 6 weeks are eligible. 22. Macroscopic hematuria 23. Hemoptysis in excess of 2.5 mL (or one half teaspoon) within 8 weeks of first dose of study drug. 24. Evidence of active bleeding or bleeding diathesis. 25. Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels and/or involvement of large pulmonary vessels by tumor 26. Prior major surgery or trauma within 14 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer. 27. Chemotherapy or radiation therapy or tumour embolization within 2 weeks prior to the first d
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I: Determination of the maximal tolerable dosis (MTD) of the combination of pazopanib and weekly topotecan Phase II: Determination of efficacy and safety of pazopanib and weekly topotecan;Secondary Objective: · Overall survival · Response rate (CR, PR) according to RECIST criteria · Clinical benefit rate (CR, PR, SD) · Duration of response · Time to progression (TTP) · Evaluation of CA-125 tumour response · Safety and tolerability · Quality of life as defined;Primary end point(s): Phase I: Dose-limiting toxicity Phase II: Progression-free survival according to RECIST criteria ;Timepoint(s) of evaluation of this end point: 12 months from end of topotecan treatment onwards | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): · Overall survival · Response rate (CR, PR) according to RECIST criteria · Clinical benefit rate (CR, PR, SD) · Duration of response · Time to progression (TTP) · Evaluation of CA-125 tumour response · Safety and tolerability · Quality of life as defined by EORTC-QLQ C 30 and Ovar 28 questionnaire;Timepoint(s) of evaluation of this end point: 12 months from end of topotecan treatment onwards | — |
Countries
Germany
Contacts
Public ContactEurop Komp-Zentr für Eierstockkrebs
Charité - Universitätsmedizin Berlin
Outcome results
None listed