A Double-Blind, Randomized Phase II Study Evaluating 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

• Register: EUCTR
• Last refreshed on: 13 May 2013
• Main ID: EUCTR2008-004429-41-NL
• Date of registration: 12/11/2008
• Prospective Registration: Yes
• Primary sponsor: Bayer Healthcare AG, D-51368 Leverkusen, Germany
• Public title: A Double-Blind, Randomized Phase II Study Evaluating 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
• Scientific title: A Double-Blind, Randomized Phase II Study Evaluating 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
• Date of first enrolment: 20/04/2009
• Target sample size: 250
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-004429-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Finland, France, Germany, Italy, Netherlands, Poland, Spain

Key inclusion & exclusion 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 (57) 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-containing
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 prior to 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.
· 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/micro liter
- Platelet count ³ 75,000/ml
. 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) as measured in international normalized ratio (INR)
and partial thromboplastin time (PTT) < 1.5 x ULN
. Serum creatinine < 1.5 x ULN.
· Women of childbearing potential must ha
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) (see Appendix 10.6), 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 ³ 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 antiepileptics).
· 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 designated ass

Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

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: 9.1 Level: LLT Classification code 10033163 Term: Ovarian epithelial cancer stage III
MedDRA version: 9.1 Level: LLT Classification code 10033164 Term: Ovarian epithelial cancer stage IV
MedDRA version: 9.1 Level: LLT Classification code 10052171 Term: Peritoneal carcinoma
MedDRA version: 9.1 Level: PT Classification code 10052171 Term: Peritoneal carcinoma

Intervention(s)

Trade Name: NEXAVAR
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: sorafenib
CAS Number: 284461-73-0
Current Sponsor code: BAY-43-9006
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

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.

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.

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 ID(s)

BAY 43-9006 / 12007