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

NCT ID: NCT00012324

Last Updated: 2013-06-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Study Classification

INTERVENTIONAL

Study Start Date

2000-09-30

Study Completion Date

2005-11-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Liver Cancer

Study Design

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Allocation Method

RANDOMIZED

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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doxorubicin hydrochloride

Intervention Type DRUG

nolatrexed dihydrochloride

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eximias Pharmaceutical

INDUSTRY

Sponsor Role lead

Principal Investigators

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Gregory R. Suplick

Role: STUDY_CHAIR

Eximias Pharmaceutical

Locations

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Arizona Clinical Research Center, Incorporated

Tucson, Arizona, United States

Site Status

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Tower Cancer Research Foundation

Beverly Hills, California, United States

Site Status

Scripps Cancer Center at Scripps Clinic

La Jolla, California, United States

Site Status

David and Donna Long Center for Cancer Treatment at Sharp Grossmont Hospital

La Mesa, California, United States

Site Status

Veterans Affairs Medical Center - Long Beach

Long Beach, California, United States

Site Status

California Pacific Medical Center - Pacific Campus

San Francisco, California, United States

Site Status

Olive View - UCLA Medical Center Foundation

Sylmar, California, United States

Site Status

California Hematology/Oncology Medical Group

Torrance, California, United States

Site Status

Helen F. Graham Cancer Center

Newark, Delaware, United States

Site Status

Lombardi Cancer Center at Georgetown University Medical Center

Washington D.C., District of Columbia, United States

Site Status

Florida Cancer Institute - Bayonet Point

Hudson, Florida, United States

Site Status

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Site Status

Oncology-Hematology Group of South Florida, P.A.

Miami, Florida, United States

Site Status

Ocala Research Institute, Incorporated

Ocala, Florida, United States

Site Status

Cancer Research Center of Hawaii

Honolulu, Hawaii, United States

Site Status

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, United States

Site Status

University of Illinois at Chicago Cancer Center

Chicago, Illinois, United States

Site Status

Holden Comprehensive Cancer Center at University of Iowa

Iowa City, Iowa, United States

Site Status

Louisiana Oncology Associates - Lafayette

Lafayette, Louisiana, United States

Site Status

Stanley S. Scott Cancer Center at Louisiana State University Medical Center - New Orleans

New Orleans, Louisiana, United States

Site Status

Alvin and Lois Lapidus Cancer Institute at Sinai Hospital

Baltimore, Maryland, United States

Site Status

University of Minnesota Cancer Center

Minneapolis, Minnesota, United States

Site Status

Saint Louis University Cancer Center

St Louis, Missouri, United States

Site Status

Siteman Cancer Center at Barnes-Jewish Hospital

St Louis, Missouri, United States

Site Status

UNMC Eppley Cancer Center at the University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Veterans Affairs Medical Center - Albuquerque

Albuquerque, New Mexico, United States

Site Status

New York Weill Cornell Cancer Center at Cornell University

New York, New York, United States

Site Status

Herbert Irving Comprehensive Cancer Center at Columbia University

New York, New York, United States

Site Status

SUNY Upstate Medical University Hospital

Syracuse, New York, United States

Site Status

Albert Einstein Cancer Center at Albert Einstein College of Medicine

The Bronx, New York, United States

Site Status

New York Medical College

Valhalla, New York, United States

Site Status

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Site Status

Albert Einstein Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Cancer Centers of the Carolinas - Eastside

Greenville, South Carolina, United States

Site Status

Medical City Dallas Hospital

Dallas, Texas, United States

Site Status

Joe Arrington Cancer Research and Treatment Center

Lubbock, Texas, United States

Site Status

St. Boniface General Hospital

Winnipeg, Manitoba, Canada

Site Status

Ottawa Hospital Regional Cancer Centre - General Campus

Ottawa, Ontario, Canada

Site Status

Princess Margaret Hospital

Toronto, Ontario, Canada

Site Status

Fundacion de Investagacion De Diego

Santurce, , Puerto Rico

Site Status

Countries

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United States Canada Puerto Rico

References

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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 doxorubicin. J Clin Oncol. 2007 Jul 20;25(21):3069-75. doi: 10.1200/JCO.2006.08.4046.

Reference Type RESULT
PMID: 17634485 (View on PubMed)

Other Identifiers

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CDR0000068506

Identifier Type: REGISTRY

Identifier Source: secondary_id

AG-337-301

Identifier Type: -

Identifier Source: secondary_id

ZARIX-ZX101-301

Identifier Type: -

Identifier Source: org_study_id

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