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

NCT00524316 | Terminated Phase 2 Results DMC

• 2 other identifiers: CDR0000563261RPCI-I-82706
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Liver Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  median progression free survival in months

  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

Secondary Outcomes (5)

• Overall Survival

  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

• 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

  Baseline, day 8, day 10, day 28 and day 35

• Safety and Tolerability

  Daily while on treatment through study completion, an average of 1 year

• Assess the Change in the Quality of Life Among Patients Using the FACTHep (Version 4) for Hepatobiliary Cancers.

  Baseline and Cycle 2

• Tumor Marker Response (AFP)

  Baseline, week 7 and every 6 weeks after

Study Arms (1)

Sunitinib

EXPERIMENTAL

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; Drug: sunitinib malate; Other: laboratory biomarker analysis; Procedure: hepatic artery embolization; Procedure: quality-of-life assessment

Interventions

doxorubicin hydrochloride DRUG

Transarterial chemoembolization

Sunitinib

sunitinib malate DRUG

Given Orally

Sunitinib

laboratory biomarker analysis OTHER

Correlative Study

Sunitinib

hepatic artery embolization PROCEDURE

Surgical procedure

Sunitinib

quality-of-life assessment PROCEDURE

Correlative Study

Sunitinib

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

MeSH Terms

Conditions

Liver Neoplasms; Carcinoma, Hepatocellular

Interventions

Doxorubicin; Sunitinib

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Due to the study's early termination and inadequate number of patients, no patients were analyzed.

Results Point of Contact

• Title: Senior Administrator, Compliance - Clinical Research Services
• Organization: Roswell Park Cancer Institute

716-845-2300

Study Officials

• Renuka Iyer, MD

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2007
• First Posted: September 3, 2007
• Study Start: April 1, 2007
• Primary Completion: December 1, 2010
• Study Completion: May 1, 2014
• Last Updated: May 9, 2017
• Results First Posted: June 4, 2014

Record last verified: 2017-03

Locations

US (1)