Nolatrexed Dihydrochloride Compared With Doxorubicin in Treating Patients With Recurrent or Unresectable Liver Cancer

Liver Cancer Clinical Trial

Official title:

A Phase III Randomized Controlled Study Comparing the Survival of Patients With Unresectable Hepatocellular Carcinoma (HCC) Treated With THYMITAQ to Patients Treated With Doxorubicin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00012324
• Other study ID #: ZARIX-ZX101-301
• Secondary ID: CDR0000068506AG-
• Status: Completed
• Phase: Phase 3
• First received: March 3, 2001
• Last updated: June 25, 2013
• Start date: September 2000
• Est. completion date: November 2005

Study information

• Verified date: October 2005
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known which chemotherapy regimen is more effective for liver cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of two different chemotherapy regimens in treating patients who have recurrent or unresectable liver cancer.

Description:

OBJECTIVES:

• Compare the overall survival in patients with unresectable or recurrent hepatocellular carcinoma treated with nolatrexed dihydrochloride vs doxorubicin.

• Compare time to progression, time to treatment failure, and response rates in patients treated with these regimens.

• Compare the probability of survival at 3, 6, 9, and 12 months in patients treated with these regimens.

• Compare the safety and clinical benefit of these regimens in these patients.

• Compare the response rates and survival of patients who have received prior therapy or no prior therapy after treatment with these two regimens.

• Compare the rates of conversion from unresectable to resectable lesions in patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to CLIP score (0-1 vs 2-3) and Karnofsky performance status (60-70% vs 80-100%). Patients are randomized to one of two treatment arms.

• Arm I: Patients receive nolatrexed dihydrochloride IV continuously on days 1-5.

• Arm II: Patients receive doxorubicin IV on day 1. Treatment continues in both arms every 3 weeks in the absence of unacceptable toxicity or disease progression.

Patients are followed every 2 months for survival.

PROJECTED ACCRUAL: Approximately 446 patients (223 per treatment arm) will be accrued for this study within 12 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: November 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically or cytologically proven or presumptive diagnosis of hepatocellular carcinoma

• Presumptive diagnosis based on rising alpha-fetoprotein (AFP) levels over 2 assessments, CT scan or MRI of liver, spiral CT scan of portal/splenic vein, and biopsy evidence of cirrhosis

• Unresectable or recurrent disease after prior surgical resection or embolization therapy

• Fibrolamellar histology allowed if considered surgically unresectable based on tumor size, extrahepatic involvement, or multiple lobe involvement

• CLIP (Cancer of the Liver Italian Program) score less than 4

• Concurrent assignment to a transplantation list allowed

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,200/mm^3

• Platelet count at least 80,000/mm^3

Hepatic:

• Bilirubin no greater than 3.0 mg/dL (except for known Gilbert's Syndrome)

• AST no greater than 5 times upper limit of normal (ULN)

• PT no greater than 1.5 times ULN

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• No uncontrolled hypertension within the past 3 months

• No unstable angina, symptomatic congestive heart failure, or myocardial infarction within the past 3 months

• No uncontrolled cardiac arrhythmia

Other:

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No active bacterial infections

• HIV negative

• No AIDS

• No other primary malignancy except carcinoma in situ of the cervix or urinary bladder or non-melanoma skin cancer

• No mental incapacitation or psychiatric illness that would preclude study participation

• No other severe disease that would preclude study participation

• Candidate for placement of a central venous access device

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Prior biologic therapy allowed

• No concurrent biologic therapy

Chemotherapy:

• No prior IV doxorubicin except intraarterial administration in locoregional therapy

Endocrine therapy:

• Prior endocrine therapy allowed

• No concurrent endocrine therapy

Radiotherapy:

• Prior radiotherapy allowed

• No concurrent radiotherapy

Surgery:

• See Disease Characteristics

• Surgery allowed if previously unresectable lesions become resectable

• Recovered from any prior surgery

• No concurrent liver transplantation

Other:

• No other concurrent investigational or marketed anticancer drugs

• No other concurrent therapy for hepatocellular carcinoma

• No concurrent terfenadine, astemizole, or cisapride that may not be interrupted during nolatrexed dihydrochloride administration

Study Design

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Liver Cancer
• Liver Neoplasms

Intervention

Drug:
• doxorubicin hydrochloride

• nolatrexed dihydrochloride

Locations

Country	Name	City	State
Canada	Ottawa Hospital Regional Cancer Centre - General Campus	Ottawa	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	St. Boniface General Hospital	Winnipeg	Manitoba
Puerto Rico	Fundacion de Investagacion De Diego	Santurce
United States	Veterans Affairs Medical Center - Albuquerque	Albuquerque	New Mexico
United States	Alvin and Lois Lapidus Cancer Institute at Sinai Hospital	Baltimore	Maryland
United States	Tower Cancer Research Foundation	Beverly Hills	California
United States	Albert Einstein Cancer Center at Albert Einstein College of Medicine	Bronx	New York
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	University of Illinois at Chicago Cancer Center	Chicago	Illinois
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Medical City Dallas Hospital	Dallas	Texas
United States	Cancer Centers of the Carolinas - Eastside	Greenville	South Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Cancer Research Center of Hawaii	Honolulu	Hawaii
United States	Florida Cancer Institute - Bayonet Point	Hudson	Florida
United States	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa
United States	Scripps Cancer Center at Scripps Clinic	La Jolla	California
United States	David and Donna Long Center for Cancer Treatment at Sharp Grossmont Hospital	La Mesa	California
United States	Louisiana Oncology Associates - Lafayette	Lafayette	Louisiana
United States	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Veterans Affairs Medical Center - Long Beach	Long Beach	California
United States	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas
United States	Oncology-Hematology Group of South Florida, P.A.	Miami	Florida
United States	University of Miami Sylvester Comprehensive Cancer Center	Miami	Florida
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota
United States	Stanley S. Scott Cancer Center at Louisiana State University Medical Center - New Orleans	New Orleans	Louisiana
United States	Herbert Irving Comprehensive Cancer Center at Columbia University	New York	New York
United States	New York Weill Cornell Cancer Center at Cornell University	New York	New York
United States	Helen F. Graham Cancer Center	Newark	Delaware
United States	Ocala Research Institute, Incorporated	Ocala	Florida
United States	UNMC Eppley Cancer Center at the University of Nebraska Medical Center	Omaha	Nebraska
United States	Albert Einstein Cancer Center	Philadelphia	Pennsylvania
United States	Saint Louis University Cancer Center	Saint Louis	Missouri
United States	Siteman Cancer Center at Barnes-Jewish Hospital	Saint Louis	Missouri
United States	California Pacific Medical Center - Pacific Campus	San Francisco	California
United States	Olive View - UCLA Medical Center Foundation	Sylmar	California
United States	SUNY Upstate Medical University Hospital	Syracuse	New York
United States	California Hematology/Oncology Medical Group	Torrance	California
United States	Arizona Clinical Research Center, Incorporated	Tucson	Arizona
United States	New York Medical College	Valhalla	New York
United States	Lombardi Cancer Center at Georgetown University Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Eximias Pharmaceutical

Countries where clinical trial is conducted

United States,  Canada,  Puerto Rico, 

References & Publications (1)

Gish RG, Porta C, Lazar L, Ruff P, Feld R, Croitoru A, Feun L, Jeziorski K, Leighton J, Gallo J, Kennealey GT. Phase III randomized controlled trial comparing the survival of patients with unresectable hepatocellular carcinoma treated with nolatrexed or d — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival			No
Secondary	Time to progression			No
Secondary	Time to treatment failure			No
Secondary	Response rate (complete response, partial response, stable disease)			No
Secondary	Survival probabilities at 3, 6, 9, and 12 months			No
Secondary	Safety			Yes
Secondary	Response to treatment in patients with and without prior therapy			No