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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier:
NCT00514228
First received: August 8, 2007
Last updated: June 25, 2012
Last verified: June 2012

August 8, 2007
June 25, 2012
July 2007
August 2008   (final data collection date for primary outcome measure)
Progression-free survival [ Time Frame: at 12 weeks ] [ Designated as safety issue: No ]
Progression-free survival at 12 weeks
Complete list of historical versions of study NCT00514228 on ClinicalTrials.gov Archive Site
  • Objective response [ Time Frame: Objective response (CR+PR) to treatment will be determined. CR or PR is to be confirmed after a minimum of 4 weeks ] [ Designated as safety issue: No ]
  • Disease stabilization (DS) [ Time Frame: Disease stabilization (CR, PR or SD) under sunitinib treatment will be determined ] [ Designated as safety issue: No ]
  • Duration of DS [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: PFS will be calculated from registration until documented tumor progression or death, whichever occurs first. ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: TTP will be calculated from registration until documented tumor progression or death due to tumor. ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: OS will be calculated from registration until death ] [ Designated as safety issue: No ]
  • Adverse events as assessed by NCI CTCAE v3.0 [ Time Frame: All AEs will be assessed according to NCI CTCAE v3.0. ] [ Designated as safety issue: Yes ]
  • Serum alpha fetoprotein level [ Time Frame: Serum AFP levels will be measured during the therapy, if AFP is ≥ 1.5 x ULN at baseline. ] [ Designated as safety issue: No ]
  • Objective response
  • Disease stabilization (DS)
  • Duration of DS
  • Progression-free survival
  • Time to progression
  • Overall survival
  • Adverse events as assessed by NCI CTCAE v3.0
  • Serum alpha fetoprotein level
  • Serum cobalamin level
Not Provided
Not Provided
 
Sunitinib in Treating Patients With Liver Cancer That Cannot Be Removed by Surgery
Continuous Sunitinib Treatment in Patients With Unresectable Hepatocellular Carcinoma A Multicenter Phase II Trial

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.

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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Liver Cancer
Drug: sunitinib malate
  • Starting dose: 37.5 mg 3 x 12.5 mg capsule
  • Reduced dose: 25 mg 2 x 12.5 mg capsule
Other Name: Sutent
Experimental: Continuous sunitinib treatment
Intervention: Drug: sunitinib malate
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 Cancer Research (SAKK) and Swiss Association for the Study of the Liver (SASL) multicenter phase II trial (SAKK 77/06). Oncologist. 2010;15(3):285-92. doi: 10.1634/theoncologist.2009-0316. Epub 2010 Mar 4. PubMed PMID: 20203173; PubMed Central PMCID: PMC3227954.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
45
February 2009
August 2008   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Switzerland
 
NCT00514228
SAKK 77/06, SWS-SAKK-77/06, EU-20750, EUDRACT-2007-003977-22, CDR0000560441
No
Swiss Group for Clinical Cancer Research
Swiss Group for Clinical Cancer Research
Not Provided
Study Chair: Dieter Koeberle, MD Cantonal Hospital of St. Gallen
Swiss Group for Clinical Cancer Research
June 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP