Efficacy and Safety Study of Sorafenib With Topotecan in Patients With Platinum-resistant Recurrent Ovarian Cancer

• Status: Completed
• Trial end date: 2015-02-01
• Target enrollment: 0
• Participant gender: Female

Summary

It is assumed, that the patients of the standard arm show a median progression-free survival time of 4.4 months those of the experimental arm of at least 6.9 months. Assuming a recruitment period of 18 months and follow-up for at least 12 months a total sample size of 174 patients is required (two-sided, α=0.05, 80% power). To account for 5% drop-outs 184 patients will be randomized.

A Data Monitoring and Safety Board (DMSB) will be established. This board will evaluate the safety profile of the drug combination after 6 patients and after 12 patients have received 1 cycle of treatment.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: JSehouli
• Treatments: Niacinamide; Sorafenib; Topotecan

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 < 6 months of a platinum-containing primary or secondary therapy) or platinum refractory (progression during primary or secondary platinum treatment) disease defined by measurable disease according to RECIST or elevated CA-125 level according the GCIG-criteria.

Definition of relapse: Demonstration of measurable or non-measurable tumour according to RECIST criteria by an imaging procedure (where applicable before relapse surgery) or increase in the tumour marker CA-125 to twice the upper laboratory value of normal for the hospital or histological confirmation of tumour relapse by biopsy or surgery.

3. No more than 2 prior treatment regimens for recurrent epithelial ovarian cancer.

4. Elevated CA-125-value before study entry in order to assess the response according the GCIG-criteria (see below). Patients without elevated CA-125 may be enrolled if they show a measurable or not-measurable disease (according RECIST) evaluated by imaging techniques (measurable disease - at least one unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan) or histologically or cytologically confirmed relapse

5. ECOG Performance Status of 0 or 1

6. ≥ 18 years age

7. The patient must be recovered from a prior operation. The operation must be performed at least 4 weeks prior to start of study drug,

8. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening

• Hemoglobin ≥ 9.0 g/dl

• Leucocyte count ≥ 3.000/micro liter

• Absolute neutrophil count (ANC) major than 1.500/micro liter

• Platelet count ≥ 100.000/micro liter

• PT-INR/PTT < 1.5 x upper limit of normal [Patients who are being therapeutically anticoagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists].

• Total bilirubin < 1,0 times the upper limit of normal

• ALT and AST < 2,5 x upper limit of normal (< 5 x upper limit of normal for patients with liver involvement of their cancer); Alkaline phosphatase < 4 x ULN

• Calculated creatinine clearance ≥ 50 ml/min or serum creatinine ≤ 1,2 x upper limit of institutional values (according to Cockcroft and Gault)

9. Life expectancy of at least 12 weeks

10. Signed and dated written informed consent before the start of specific protocol procedures.

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.

Excluded therapies and medications, previous and concomitant:

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 investigational 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