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

Swiss Group for Clinical Cancer Research

Status and phase

Completed

Phase 2

Conditions

Liver Cancer

Treatments

Drug: sunitinib malate

Study type

Interventional

Funder types

Other

Identifiers

NCT00514228

CDR0000560441

EUDRACT-2007-003977-22

SAKK 77/06

EU-20750

SWS-SAKK-77/06

Details and patient eligibility

About

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.

Full 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.

Enrollment

45 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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