Sunitinib in Treating Patients With Liver Cancer That Cannot Be Removed by Surgery

Liver Cancer Clinical Trial

Official title:

Continuous Sunitinib Treatment in Patients With Unresectable Hepatocellular Carcinoma A Multicenter Phase II Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00514228
• Other study ID #: SAKK 77/06
• Secondary ID: SWS-SAKK-77/06EU
• Status: Completed
• Phase: Phase 2
• First received: August 8, 2007
• Last updated: June 25, 2012
• Start date: July 2007
• Est. completion date: February 2009

Study information

• Verified date: June 2012
• Source: Swiss Group for Clinical Cancer Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well sunitinib works in treating patients with liver cancer that cannot be removed by surgery.

Description:

OBJECTIVES:

Primary

• Demonstrate the antitumor activity of continuous sunitinib malate treatment in patients with unresectable hepatocellular carcinoma.

Secondary

• Evaluate the safety of sunitinib malate treatment.

• Measure serum cobalamin (i.e., vitamin B12) level during sunitinib malate treatment in order to investigate the relationship between sunitinib malate treatment and cobalamin deficiency.

• Control the cobalamin deficiency by cobalamin replacement.

• Investigate whether changes in tumor density could be used as a criterion for tumor response in future trials.

OUTLINE: This is a multicenter study.

Patients receive oral sunitinib malate once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients undergo blood sample collection on day 1 of each course to assess serum cobalamin levels and correlation with sunitinib malate treatment. Patients are also assessed for changes in tumor density and correlation with response. Baseline CT scans are compared with scans performed at 6 and 12 weeks to evaluate changes in CT-scan density due to tumor necrosis and response.

After completion of study therapy, patients are followed at least every 3 months for up to 3 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: February 2009
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

Inclusion criteria:

• Histologically, cytologically, or radiologically confirmed hepatocellular carcinoma (HCC) meeting 1 of the following criteria:

• Localized, surgically unresectable disease

• Candidates for radical surgery for locally advanced disease are excluded

• Metastatic disease

• Measurable disease, defined as = 1 lesion, outside of pretreated areas, that can be measured in = 1 dimension as = 10 mm by spiral or multi-slice CT scan or MRI

• Child-Pugh class A or mildly decompensated Child-Pugh class B liver dysfunction

Exclusion criteria:

• Clinical ascites of any grade

• Clinical symptoms or history of CNS metastases or leptomeningeal disease

• Known fibrolamellar HCC or mixed cholangiocarcinoma and HCC

PATIENT CHARACTERISTICS:

Inclusion criteria:

• WHO performance status 0-1

• Hemoglobin = 9.0 g/dL

• Absolute neutrophil count = 1,500/mm³

• Platelet count = 75,000/mm³

• Bilirubin = 2 times upper limit of normal (ULN)

• ALT = 7 times ULN

• Albumin = 2.5 g/dL

• Creatinine clearance = 40 mL/min

• Quick test = 50% (adequate coagulation)

• Urine dipstick for proteinuria < 2+ OR = 1 g of protein in 24-hour urine collection

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 12 months after completion of study therapy

Exclusion criteria:

• Pregnant or nursing

• Encephalopathy

• Malignancy within the past 5 years except for adequately treated cervical carcinoma in situ or localized nonmelanoma skin cancer

• Hemorrhagic or thrombotic cerebrovascular event in the past 12 months

• Documented variceal hemorrhage within the past 3 months

• History or presence of clinically significant acute or unstable cardiovascular, cerebrovascular, renal, gastrointestinal, pulmonary, immunological (except for the presence of hepatitis B virus, hepatitis C virus, or cirrhosis), endocrine, or central nervous system disorders

• Known HIV infection

• Active infection requiring IV antibiotics

• Arterial hypertension = 150/100 mm Hg, despite therapy

• Ongoing cardiac dysrhythmias = grade 2

• Atrial fibrillation of any grade

• Prolongation of QTc > 500 msec in screening ECG or history of familial long QT syndrome

• Inability to take oral medications

• Psychiatric disorder precluding understanding of information of study-related topics, giving informed consent, or interfering with compliance for oral drug intake

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

• At least 4 weeks since prior surgery or liver-directed therapy (e.g., transarterial embolization/chemoembolization [limited to 5 treatments], radiofrequency ablation, cryoablation, radiotherapy, or percutaneous ethanol injection)

• Previously treated lesions must remain separate from those to be measured in the present study

• Low-dose anticoagulants for maintenance of patency of central venous access or prevention of deep vein thrombosis allowed

Exclusion criteria:

• Prior systemic anticancer treatment for hepatocellular carcinoma

• Prior organ transplantation

• Treatment in a clinical study within the past 30 days

• Concurrent full-dose anticoagulant or requirement for anticoagulant therapy

• Concurrent experimental drugs or other anticancer therapy

• Concurrent use or anticipated need for CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, voriconazole, erythromycin, clarithromycin, and protease inhibitors)

• Concurrent CYP3A4 inducers (e.g., carbamazepine, continuous treatment with dexamethasone [> 2 mg/day for > 7 days], phenobarbital, phenytoin, rifampicin, and St John's wort)

• Concurrent antacids allowed provided they are administered > 1 hour before or > 1 hour after study drug

• Concurrent elective major surgery

• Concurrent radiotherapy

• Concurrent analgesic radiotherapy of nontarget lesions allowed

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Liver Cancer
• Liver Neoplasms

Intervention

Drug:
• sunitinib malate
Starting dose: 37.5 mg 3 x 12.5 mg capsule Reduced dose: 25 mg 2 x 12.5 mg capsule

Locations

Country	Name	City	State
Switzerland	Kantonsspital - St. Gallen	St. Gallen

Sponsors (1)

Lead Sponsor	Collaborator
Swiss Group for Clinical Cancer Research

Country where clinical trial is conducted

Switzerland, 

References & Publications (1)

Koeberle D, Montemurro M, Samaras P, Majno P, Simcock M, Limacher A, Lerch S, Kovàcs K, Inauen R, Hess V, Saletti P, Borner M, Roth A, Bodoky G. Continuous Sunitinib treatment in patients with advanced hepatocellular carcinoma: a Swiss Group for Clinical — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival		at 12 weeks	No
Secondary	Objective response		Objective response (CR+PR) to treatment will be determined. CR or PR is to be confirmed after a minimum of 4 weeks	No
Secondary	Disease stabilization (DS)		Disease stabilization (CR, PR or SD) under sunitinib treatment will be determined	No
Secondary	Duration of DS		Duration of DS (CR, PR or SD) will be calculated from the time that measurement criteria are met for the first time until documented tumor progression	No
Secondary	Progression-free survival		PFS will be calculated from registration until documented tumor progression or death, whichever occurs first.	No
Secondary	Time to progression		TTP will be calculated from registration until documented tumor progression or death due to tumor.	No
Secondary	Overall survival		OS will be calculated from registration until death	No
Secondary	Adverse events as assessed by NCI CTCAE v3.0		All AEs will be assessed according to NCI CTCAE v3.0.	Yes
Secondary	Serum alpha fetoprotein level		Serum AFP levels will be measured during the therapy, if AFP is = 1.5 x ULN at baseline.	No