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

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00012324
First received: March 3, 2001
Last updated: June 25, 2013
Last verified: October 2005
  Purpose

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.


Condition Intervention Phase
Liver Cancer
Drug: doxorubicin hydrochloride
Drug: nolatrexed dihydrochloride
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to progression [ Designated as safety issue: No ]
  • Time to treatment failure [ Designated as safety issue: No ]
  • Response rate (complete response, partial response, stable disease) [ Designated as safety issue: No ]
  • Survival probabilities at 3, 6, 9, and 12 months [ Designated as safety issue: No ]
  • Safety [ Designated as safety issue: Yes ]
  • Response to treatment in patients with and without prior therapy [ Designated as safety issue: No ]

Study Start Date: September 2000
Study Completion Date: November 2005
Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00012324

  Show 42 Study Locations
Sponsors and Collaborators
Eximias Pharmaceutical
Investigators
Study Chair: Gregory R. Suplick Eximias Pharmaceutical
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00012324     History of Changes
Other Study ID Numbers: ZARIX-ZX101-301, CDR0000068506, AG-337-301
Study First Received: March 3, 2001
Last Updated: June 25, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
localized unresectable adult primary liver cancer
advanced adult primary liver cancer
recurrent adult primary liver cancer
adult primary hepatocellular carcinoma

Additional relevant MeSH terms:
Liver Neoplasms
Carcinoma, Hepatocellular
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Liver Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Doxorubicin
Liposomal doxorubicin
Nolatrexed
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Folic Acid Antagonists

ClinicalTrials.gov processed this record on August 28, 2014