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

Phase 3
18 Years
Not Enrolling
Liver Cancer

Thank you

Trial Information

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


- 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.

Inclusion Criteria


- Histologically or cytologically proven or presumptive diagnosis of hepatocellular

- 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

- 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



- 18 and over

Performance status:

- Karnofsky 60-100%

Life expectancy:

- Not specified


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

- Platelet count at least 80,000/mm^3


- 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


- Creatinine no greater than 2.0 mg/dL


- 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


- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No active bacterial infections

- HIV negative


- 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

- No other severe disease that would preclude study participation

- Candidate for placement of a central venous access device


Biologic therapy:

- Prior biologic therapy allowed

- No concurrent biologic therapy


- No prior IV doxorubicin except intraarterial administration in locoregional therapy

Endocrine therapy:

- Prior endocrine therapy allowed

- No concurrent endocrine therapy


- Prior radiotherapy allowed

- No concurrent radiotherapy


- See Disease Characteristics

- Surgery allowed if previously unresectable lesions become resectable

- Recovered from any prior surgery

- No concurrent liver transplantation


- 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

Type of Study:


Study Design:

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

Outcome Measure:

Overall survival

Safety Issue:


Principal Investigator

Gregory R. Suplick

Investigator Role:

Study Chair

Investigator Affiliation:

Eximias Pharmaceutical


United States: Federal Government

Study ID:




Start Date:

September 2000

Completion Date:

November 2005

Related Keywords:

  • Liver Cancer
  • localized unresectable adult primary liver cancer
  • advanced adult primary liver cancer
  • recurrent adult primary liver cancer
  • adult primary hepatocellular carcinoma
  • Liver Neoplasms
  • Carcinoma, Hepatocellular



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