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

NCT01047891 | Completed Phase 2 DMC

• 1 other identifier: TRIAS 2009
• Study Type: interventional
• Target: 174
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Ovarian Cancer

Outcome Measures

Primary Outcomes (1)

• Primary objective: Determination of the progression-free survival (PFS) of patients treated with topotecan and sorafenib versus topotecan and placebo

  The primary target value of this study is the comparison of the median progression-free survival time between the two study arms. Progression-free survival time (PFS) of a patient is defined as the time in months from start of the first therapy cycle until PD or death is observed

  18 months

Secondary Outcomes (6)

• Overall survival

  18 months

• Response rate

  18 months

• Duration of response

  18 months

• Time to progression (TTP)

  18 months

• Safety and tolerability

  18 months

Study Arms (1)

Experimental

EXPERIMENTAL

Drug: Sorafenib

Interventions

Sorafenib DRUG

Topotecan 1,25 mg/m²/d administered as an i.v. infusion over 30 minutes once daily on days 1-5, every 21 days and Sorafenib 400 mg orally twice daily (total daily dose 800 mg) administered

Also known as: Nexavar®

Experimental

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically confirmed epithelial ovarian cancer, primary peritoneal carcinomatosis or fallopian tube cancer
• 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.
• No more than 2 prior treatment regimens for recurrent epithelial ovarian cancer.
• 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
• ECOG Performance Status of 0 or 1
• ≥ 18 years age
• The patient must be recovered from a prior operation. The operation must be performed at least 4 weeks prior to start of study drug,
• 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

You may not qualify if:

• 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
• 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
• 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
• Known or suspected hypersensitivity reaction to topotecan or any ingredient of topotecan or sorafenib or any ingredient of sorafenib
• Active clinically serious infections (\> grade 2 NCI-CTC version 3.0)
• History of HIV infection or chronic hepatitis B or C
• History of organ allograft
• Patients with history of colon perforation
• Patients with history of colitis or neutropenia colitis
• Patients with evidence or history of bleeding diathesis
• Serious non healing wound, fracture or ulcer
• Patients undergoing renal dialysis
• Patients unable to swallow oral medications
• Significant disease which, in the investigator's opinion, would exclude the patient from the study
• Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results

Sponsors & Collaborators

• JSehouli: lead

Study Sites (1)

Charité Campus Virchow-Klinikum

Berlin, State of Berlin, 13355, Germany

Location

Related Publications (2)

• Gaitskell K, Rogozinska E, Platt S, Chen Y, Abd El Aziz M, Tattersall A, Morrison J. Angiogenesis inhibitors for the treatment of epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Apr 18;4(4):CD007930. doi: 10.1002/14651858.CD007930.pub3.

  PMID: 37185961 DERIVED

• Chekerov R, Hilpert F, Mahner S, El-Balat A, Harter P, De Gregorio N, Fridrich C, Markmann S, Potenberg J, Lorenz R, Oskay-Oezcelik G, Schmidt M, Krabisch P, Lueck HJ, Richter R, Braicu EI, du Bois A, Sehouli J; NOGGO; AGO TRIAS Investigators. Sorafenib plus topotecan versus placebo plus topotecan for platinum-resistant ovarian cancer (TRIAS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2018 Sep;19(9):1247-1258. doi: 10.1016/S1470-2045(18)30372-3. Epub 2018 Aug 9.

  PMID: 30100379 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Jalid Sehouli Sehouli, Professor

  Charité Campus Virchow-Klinikum, Berlin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. med

Study Record Dates

• First Submitted: January 12, 2010
• First Posted: January 13, 2010
• Study Start: January 1, 2010
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: February 18, 2015

Record last verified: 2015-02

Locations

DE (1)