A MULTINATIONAL, RANDOMIZED, OPEN-LABEL, PHASE 3 STUDY OF SUNITINIB MALATE VERSUS SORAFENIB IN PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA

• Register: EUCTR
• Last refreshed on: 26 June 2012
• Main ID: EUCTR2007-006637-14-PT
• Date of registration: 23/12/2009
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc. - 235 East 42nd Street - New York - 10017
• Public title: A MULTINATIONAL, RANDOMIZED, OPEN-LABEL, PHASE 3 STUDY OF SUNITINIB MALATE VERSUS SORAFENIB IN PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA
• Scientific title: A MULTINATIONAL, RANDOMIZED, OPEN-LABEL, PHASE 3 STUDY OF SUNITINIB MALATE VERSUS SORAFENIB IN PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA
• Date of first enrolment: 05/03/2010
• Target sample size: 1200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-006637-14
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Belgium, Czech Republic, France, Germany, Hungary, Italy, Portugal, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Histologically-confirmed diagnosis of hepatocellular carcinoma that is locally advanced or metastatic (histological diagnosis obtained from a prior tumor biopsy specimen is acceptable).
2. Measurable disease according to RECIST. At least one target lesion should not have previously received any local therapy, such as surgery, radiation therapy, hepatic arterial embolization, TACE, hepatic arterial infusion, radio-frequency ablation, percutaneous ethanol injection or cryoablation, unless it has subsequently progressed according to RECIST.
3. Resolution of all acute toxic effects of any prior local treatment to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 grade =1.
4. Child-Pugh class A (for the determination of the Child-Pugh class, use the table reported in Appendix 5 of the protocol).
5. Eighteen years of age or older.
6. ECOG performance status 0 or 1.
7. Required baseline laboratory data within the following parameters:
• Neutrophils = 1,500/µL
• Platelets = 75,000/µL
• Hemoglobin = 9.0 g/dL
• Serum aspartate aminotransferase (AST; serum glutamate-oxalate transferase [SGOT]) and serum alanine aminotransferase (ALT; serum glutamate-pyruvate transferase [SGPT]) = 5 x ULN
• Serum creatinine = 1.5 x ULN
• INR <1.7 or prothrombin time (PT) < 4 seconds above ULN
• Serum albumin > 3.5 g/dL (* = 2.8 g/dL)
• Total bilirubin < 2 mg/dL (* = 3 mg/dL)
* ONLY ONE of these 2 last criteria may have a score of 2 according to the Child-Pugh scoring system.
8. Candidate for treatment with sorafenib. Safety precautions as detailed in sorafenib package insert or equivalent documentation but not stated in study entry criteria must be ensured by the investigator prior to randomization (e.g. sorafenib is contraindicated in patients with known severe hypersensitivity to sorafenib or any other component of NEXAVAR®).
9. Signed and dated informed consent indicating that the patient (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrollment.
10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including completion of patient-reported outcome (PRO) questionnaires.
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Prior systemic treatment for HCC, including prior treatment with sunitinib, or sorafenib, or another investigational agent.
2. Any prior local therapy (such as surgery, radiation therapy, hepatic arterial embolization, TACE, hepatic arterial infusion, radiofrequency ablation, percutaneous ethanol injection or cryoablation) within 4 weeks of study entry.
3. Prior history of liver transplant.
4. Presence of clinically relevant ascites (e.g., requiring therapeutic paracentesis or that can be classified as Child-Pugh score = 2).
5. NCI CTCAE grade = 3 hemorrhage within 4 weeks of starting study treatment, or documented variceal hemorrhage of any grade within 12 months of study entry (as documented by endoscopy).
6. Presence of esophageal varices at risk of bleeding and/or serious or non-healing wound/ulcer (as documented by endoscopy).
7. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of study entry.
8. Any of the following within the 12 months prior to study drug administration: severe/unstable angina, myocardial infarction, coronary artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, including transient ischemic attack, or pulmonary embolism.
9. Diagnosis of any second malignancy within the last 3 years, except basal cell carcinoma, squamous cell skin cancer, or in situ carcinoma of the cervix uteri that has been adequately treated without evidence of recurrent disease for 12 months.
10. History of or known brain metastases, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease.
11. Ongoing cardiac dysrhythmias of NCI CTCAE grade = 2, atrial fibrillation of any grade, or prolongation of the QTc interval to > 450 msec for males or > 470 msec for females.
12. Hypertension that cannot be controlled by medications (blood pressure >150/100 mm Hg despite optimal medical therapy).
13. Treatment with potent CYP3A4 inhibitor within 7 days of study entry or with potent CYP3A4 inducer within 12 days of study entry.
14. Concomitant treatment with botanical formulation having an approved indication for cancer treatment, such as “Xiao Chai Hu Tang”, “Kanglaite”, etc.
15. Ongoing treatment with therapeutic levels of coumarin derivatives or oral anti-vitamin K agents.
16. Inability to swallow oral medications, or presence of active inflammatory bowel disease, partial or complete bowel obstruction or chronic diarrhea.
17. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
18. Pregnancy or breastfeeding. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) within the 7 days prior to study enrollment.
19. Fertile patients unwilling or unable to use adequate contraception, as defined in Life Style Guidelines, Section 4.4, to prevent pregnancy during the study.
20. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Advanced Hepatocellular Carcinoma
MedDRA version: 9.1 Level: LLT Classification code 10049010 Term: Carcinoma hepatocellular

Intervention(s)

Trade Name: Sutent
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Sunitinib Malate
CAS Number: 341031-54-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 12.5-

Trade Name: NEXAVAR
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Sunitinib malate
CAS Number: 284461-73-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Trade Name: Sutent
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Sunitinib Malate
CAS Number: 341031-54-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Primary Outcome(s)

Secondary Objective: • To compare PFS and TTP between both treatment arms
• To evaluate the safety and tolerability of sunitinib in this patient population
• To compare patients’ health status between both treatment arms.

Primary end point(s): Overall Survival (OS)

Main Objective: To demonstrate that OS on sunitinib is superior or equivalent to OS on sorafenib in patients with advanced hepatocellular carcinoma

Secondary ID(s)

A6181170

2007-006637-14-GB