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

• ClinicalTrials.gov Identifier: NCT00524316
• Recruitment Status: Terminated
• First Posted: September 3, 2007
• Results First Posted: June 4, 2014
• Last Update Posted: May 9, 2017
• Sponsor: Roswell Park Cancer Institute
• Information provided by (Responsible Party): Roswell Park Cancer Institute

Study Description

Brief 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. Chemoembolization kills tumor cells by blocking the blood flow to the tumor and keeping chemotherapy drugs, such as doxorubicin, near the tumor. Giving sunitinib together with chemoembolization may kill more tumor cells.

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

Condition or disease	Intervention/treatment	Phase
Liver Cancer	Drug: doxorubicin hydrochloride; Drug: sunitinib malate; Other: laboratory biomarker analysis; Procedure: hepatic artery embolization; Procedure: quality-of-life assessment	Phase 2

Detailed Description:

OBJECTIVES:

Primary

• To determine the progression-free survival at 4 months of patients treated with this regimen.

Secondary

• To determine overall survival of these patients.
• To determine if dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can be used to measure decrease in tumor perfusion and vascular permeability as a result of treatment with sunitinib malate in combination with TACE, and if it can be useful in prognosis.
• To examine the safety and tolerability of this regimen.
• To determine if a change in circulating endothelial precursor cell number and total monocyte count on days 3, 8, 10, and 35 of therapy (as compared with levels at baseline) and decrease in soluble vascular endothelial growth factor receptor-2 in serum on days 8 (before TACE), 10, and 35 of therapy (as compared with baseline) correlate with improved response and survival.
• To determine the effect of this therapy on quality of life as measured by the FACT-HEP scale prior to each course of therapy.

OUTLINE: This is a multicenter study.

Patients receive oral sunitinib malate once daily on days 1-7 and 15-35 in course 1 and on days 1-28 in all subsequent courses. Patients undergo hepatic artery chemoembolization with doxorubicin hydrochloride on day 8 of course 1 only. Treatment with sunitinib malate repeats every 6 weeks* in the absence of disease progression or unacceptable toxicity.

NOTE: *Course 1 is 7 weeks in duration; all subsequent courses are 6 weeks in duration.

Blood samples are collected at baseline and periodically during study to measure circulating endothelial precursor cell levels, total monocyte count, and soluble vascular endothelial growth factor receptor-2.

Quality of life is assessed by the FACT-HEP scale at baseline, prior to each course of treatment, and then at the completion of treatment.

After completion of study treatment, patients are followed every 6 months.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of SUNITINIB MALATE (Sutent) and Chemoembolization in Patients With Unresectable Hepatocellular Cancer
• Study Start Date: April 2007
• Actual Primary Completion Date: December 2010
• Actual Study Completion Date: May 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Sunitinib; oral sunitinib malate once daily on days 1-7 and 15-35 in course 1 and on days 1-28 in all subsequent courses	Drug: doxorubicin hydrochloride; Transarterial chemoembolization; Drug: sunitinib malate; Given Orally; Other: laboratory biomarker analysis; Correlative Study; Procedure: hepatic artery embolization; Surgical procedure; Procedure: quality-of-life assessment; Correlative Study

Outcome Measures

Primary Outcome Measures :

1. Progression-free Survival [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months ]
   median progression free survival in months

Secondary Outcome Measures :

1. Overall Survival [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months ]
   median survival in months
2. Tissue Perfusion, Ktrans, IAUC, and Percent Viable Tumor as Measured by DCE-MRI at Baseline and on Days 8 (Before Transarterial Chemoembolization), 10, and 35 [ Time Frame: Baseline, day 8, day 10, day 28 and day 35 ]
3. Safety and Tolerability [ Time Frame: Daily while on treatment through study completion, an average of 1 year ]

   Number of participants with adverse advent.

   Please refer to adverse event reporting for more detail.

4. Assess the Change in the Quality of Life Among Patients Using the FACTHep (Version 4) for Hepatobiliary Cancers. [ Time Frame: Baseline and Cycle 2 ]

   We utilized the FACT-HEP TOTAL SCORE (version 4) quality-of-life scale, which is a 45 item scale ranging from 96-178. Higher scores reflect better quality of life.

   No subscales were analyzed.

5. Tumor Marker Response (AFP) [ Time Frame: Baseline, week 7 and every 6 weeks after ]
   Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 120 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

DISEASE CHARACTERISTICS:

• Histologically, cytologically, or serologically* confirmed hepatocellular carcinoma meeting the following criteria:

  • 1-4 lesions
  • Involvement of 1 or both liver lobes NOTE: *Alpha-fetoprotein (AFP) > 500 mcg/L in high-risk patients

• Measurable disease by CT scan or MRI

  • Disease does not exceed 50% of the liver parenchyma
  • At least 1 lesion ≥ 3 cm in longest diameter
• Tumor burden involves < 50% of the liver

• Refused surgery OR unresectable disease due to any of the following:

  • Multifocality
  • Advanced cirrhosis
  • Comorbid illness
• Candidate for chemoembolization
• No fibrolamellar histology
• No ascites
• No known brain metastases

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 12 weeks
• WBC ≥ 3,000/mm³
• ANC ≥ 1,500/mm³
• Hemoglobin ≥ 8.5 g/dL (transfusion allowed)
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 2 mg/dL
• AST ≤ 5 times upper limit of normal (ULN)
• INR < 1.5
• Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 30 mL/min
• No bleeding diathesis or coagulopathy
• No active congestive heart failure
• No uncontrolled angina
• No myocardial infarction within the past 12 months
• No cardiac arrhythmia
• Ejection fraction ≥ 45% (in patients with known coronary artery disease and in patients > 50 years of age)
• Child-Pugh class A or B cirrhosis
• No impedance of hepatopedal blood flow (portal vein thrombosis)
• No thrombosis of the main portal vein
• No encephalopathy
• No biliary obstruction
• No variceal bleed within the past 6 months
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib malate
• No absolute contraindication to doxorubicin, iodinated contrast material, microfibrillar collage hemostat, or dexamethasone

• No other concurrent uncontrolled illness including, but not limited to, any of the following:

  • Ongoing or active infection
  • Psychiatric illness or social situation that would limit compliance with study requirements
• No other active malignancies within the past year except nonmelanoma skin cancer or carcinoma in situ
• No significant traumatic injury within the past 4 weeks
• No QTc prolongation (i.e., QTc interval ≥ 500 msec) or other significant ECG abnormalities
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after the completion of study treatment

PRIOR CONCURRENT THERAPY:

• Recovered from prior therapy

• Prior liver-directed therapy, such as chemoembolization, radiofrequency ablation, cryoablation, or ethanol injection allowed if the following criteria are met:

  • Treated lesion remains inactive by CT scan or MRI and new lesion being embolized is distinct from the previously treated lesion
  • Radiographic progression of previously treated lesion requiring re-embolization
• Prior liver resection allowed
• Prior immunotherapy allowed
• No prior antiangiogenesis therapy

• No prior liver transplantation

  • Patients awaiting a cadaveric or orthotopic liver transplantation are eligible provided they have end-stage liver disease with a priority score of < 20 points
• More than 4 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas or mitomycin C)
• More than 4 weeks since prior major surgery or open biopsy
• At least 1 week since prior fine needle biopsy
• No concurrent immunotherapy
• No concurrent radiotherapy
• No concurrent combination antiretroviral therapy for HIV-positive patients

• No concurrent therapeutic doses of coumarin-derivative anticoagulants (e.g., warfarin)

  • Doses of ≤ 1 mg/day are allowed for prophylaxis of thrombosis as long as INR ≤ 1.5
  • Both full dose and prophylactic dose low molecular weight heparin allowed as long as PT INR ≤ 1.5
• No anticipated major surgery during and for 3 months after completion of study treatment
• No other concurrent investigational agents
• No other concurrent anticancer therapy

Contacts and Locations

Locations

United States, New York

Roswell Park Cancer Institute

Buffalo, New York, United States, 14263-0001

Sponsors and Collaborators

Roswell Park Cancer Institute

Investigators

• Principal Investigator: Renuka Iyer, MD; Roswell Park Cancer Institute

More Information

• Responsible Party: Roswell Park Cancer Institute
• ClinicalTrials.gov Identifier: NCT00524316
• Other Study ID Numbers: CDR0000563261; RPCI-I-82706
• First Posted: September 3, 2007
• Results First Posted: June 4, 2014
• Last Update Posted: May 9, 2017
• Last Verified: March 2017

Keywords provided by Roswell Park Cancer Institute:

adult primary hepatocellular carcinoma; advanced adult primary liver cancer; localized unresectable adult primary liver cancer; recurrent adult primary liver cancer

Additional relevant MeSH terms:

Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases; Doxorubicin; Liposomal doxorubicin; Sunitinib; Antibiotics, Antineoplastic; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Protein Kinase Inhibitors