The study population will include patients with FIGO stage III or IV ovarian cancer or primary peritoneal cancer who have had extensive debulkment surgery and who have achieved a clinical complete response (disappearance of all clinical and radiological evidence of tumor) after one regimen of standard platinum/taxane-based chemotherapy for whom treatment with sorafenib is considered medically acceptable. MedDRA version: 14.1 Level: LLT Classification code 10052171 Term: Peritoneal carcinoma Sys
Conditions
Sponsors
Bayer Healthcare AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patients must be able and willing to sign a written informed consent. A signed informed consent must be appropriately obtained prior to any study specific procedures. • Age =18 years. • Histologically confirmed FIGO stage III or IV ovarian epithelial cancer or primary peritoneal cancer at presentation. Patients must have achieved a clinical complete response (disappearance of all clinical and radiological evidence of tumor) after only one regimen (4-8 cycles) of platinum and taxane-based standard chemotherapy received after tumor debulkment. Details for chemotherapy and surgical debulkment are as follows: -Standard debulking surgery: Surgery followed by one regimen (4-8 cycles) of platinum and taxane-containing standard chemotherapy received after tumor debulkment. -Interval surgical debulkment: Interval debulking will be defined as debulking surgery that is performed after a minimum of 2 cycles of platinum/taxane containing chemotherapy, or after a maximum of 6 cycles of chemotherapy. All patients who undergo interval debulking must subsequently complete at least 2 additional cycles of chemotherapy after debulking, and all must complete the required 4-8 cycles of chemotherapy. -There is to be only one debulking procedure per patient. -The taxane and platinum compounds used for either intravenous or intraperitoneal treatment can be replaced with another taxane or platinum compound, respectively. Dosing and timing of the treatment cycles (e.g. 3-weekly or 4 weekly) may vary at the discretion of the clinical investigator. -Intraperitoneal chemotherapy is not allowed for patients undergoing interval debulking. For patients with optimally debulked residual disease following standard debulking surgery (largest tumor nodule = 1.0 cm), intraperitoneal chemotherapy can be applied. -No more than 6 intraperitoneal treatment cycles are allowed. -Cross-over from intraperitoneal chemotherapy to standard intravenous taxane/platinum chemotherapy is allowed at any time. However, the total number of treatment cycles, no matter what modality, must not exceed 8. -Complete clinical response will be documented via an eligibility scan that is performed after completion of required chemotherapy. No previous chemotherapy can be administered except for the one regimen of IV/IP chemotherapy for ovarian or primary peritoneal cancer. • Normal serum CA125 level within 14 days of first dose of the study drug. • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. • All scans used to document complete response must be done within 42 days prior to randomization. • Eligibility scan must be completed within 60 days of the date of the last dose of chemotherapy. All scans used to document complete response must be done within 42 days prior randomization • Patients must be able to swallow and retain oral medication. • Life expectancy of at least 12 weeks. • Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 14 days prior to randomization: - Hemoglobin =8.5 g/dl - Absolute neutrophil count (ANC) =1,500/µl - Platelet count = 75,000/µl - Total bilirubin = 1.5 times the upper limit of normal - Alanine aminotransaminase (ALT) and Aspartate aminotransferase (AST) = 2.5 x upper limit of normal - Alkaline phosphatase = 4 x upper limit of normal (ULN) - Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin t
Exclusion criteria
Exclusion criteria: • Patients with any residual cancer tissue after the completion of chemotherapy detectable by standard CT or magnetic resonance imaging (MRI). • Prior local radiotherapy, neoadjuvant chemotherapy or hormonal or any other systemic treatment other than that specified in the protocol for any current or prior diagnosis of ovarian or primary peritoneal cancer. Single-agent weekly paclitaxel will not be considered standard for the purpose of this trial, and is therefore excluded. • Male sex. • Patients with more than one surgical procedure for ovarian or peritoneal cancer. This does not refer to diagnostic biopsies, but does exclude second-look operations. • Histologic subtypes of ovarian cancer other than epithelial (i.e. sarcoma, lymphoma, germ cell). • Major surgery, open biopsy, or significant traumatic injury within 30 days prior to randomization. • Non-healing wound, ulcer, or bone fracture. • Evidence or history of bleeding diathesis or coagulopathy. • Clinically significant cardiac disease including congestive heart failure > class II New York Heart Association (NYHA), unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months) or myocardial infarction within the past 6 months prior to randomization. • Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy or uncontrolled hypertension (systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg) despite optimal medical management. • Thrombotic or embolic venous or arterial events, such as a cerebrovascular accident, including transient ischemic attacks and pulmonary embolism within the past 6 months. • Hemorrhage/bleeding event = NCI-Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 within 30 days of randomization. • Infection > NCI-CTCAE Grade 2. • Known human immunodeficiency virus infection or infection with hepatitis B or C. • Previous or concurrent cancer that is distinct in primary site or histology from ovarian or primary peritoneal cancer within 5 years prior to randomization EXCEPT cervical cancer in situ, treated basal cell carcinoma and superficial bladder tumors [Ta (Non invasive tumor), Tis (Carcinoma in situ) and T1 (Tumor invades lamina propria)]. • Known or suspected allergy to sorafenib or hypersensitivity to sorafenib or any agent given in the course of this trial. • Patients with seizure disorder requiring medication (such as steroids or anti-epileptics). • Patients undergoing renal dialysis. • Substance abuse, medical, psychological or social conditions that may interfere with the patient’s participation in the study or evaluation of the study results. • Unresolved toxicity (i.e. neurotoxicity) attributed to the required chemotherapy higher than NCI-CTCAE (version 3) Grade 2 (excluding cases of alopecia). • Patients unable to swallow oral medications. • Any malabsorption condition. • Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study. • Known brain metastasis. Patients with unexplained neurological symptoms will undergo a CT scan/MRI of the brain to exclude brain metastasis. • Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 14 days of the start of treatment, and must use adequate birth control measures during the course of the trial. The definition of effective contraception will be based on the judgment of the principal investigator or a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of this study is to evaluate the efficacy and safety of sorafenib compared to placebo in Ovarian Epithelial Cancer or Primary Peritoneal Cancer patients who have achieved a complete clinical response after standard platinum/taxane containing chemotherapy. The primary objective is to compare the treatment groups in terms of progression free survival (PFS) which in this setting is based on time to CT-documented relapse.;Secondary Objective: The secondary objectives include the time to first pathologic CA125 serum levels (needs to be confirmed with a second measurement within 2 weeks), the overall survival (OS), the ovarian cancer symptom response, the general health status and the safety.;Primary end point(s): The primary efficacy endpoint is Progression-Free Survival (PFS), which is defined as the time from randomization to tumor progression (radiological or clinical, whichever is earlier) or death (for those who die prior to documented progression). Patients alive without documented progression at the time of analysis will be censored at their last date of tumor evaluation. | — |
Countries
Belgium, Canada, Finland, France, Germany, Hong Kong, Italy, Japan, Korea, Democratic People's Republic of, Netherlands, Poland, Singapore, Spain, United States
Contacts
Public ContactBayer Clin. Trials Contact CTP Team
Bayer HealthCare AG
Outcome results
None listed