Liver CancerPhase 3NCT00012324
Nolatrexed Dihydrochloride Compared With Doxorubicin in Treating Patients With Recurrent or Unresectable Liver Cancer
A Phase 3 study testing doxorubicin hydrochloride and nolatrexed dihydrochloride in people with Liver Cancer, run by Eximias Pharmaceutical at 42 sites in 3 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Cancer
- What is being tested?
- doxorubicin hydrochloride and nolatrexed dihydrochloride
- How many people
- Not given
- Where
- 42 sitesin 3 countries
- Study dates
- Sep 2000to Nov 2005
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
42 sites in 3 countries.
42 sites in 3 countries
United States38 sites
Veterans Affairs Medical Center - Albuquerque
Albuquerque, New Mexico, 87108
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
Baltimore, Maryland, 21215
Tower Cancer Research Foundation
Beverly Hills, California, 90211
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, 60611
University of Illinois at Chicago Cancer Center
Chicago, Illinois, 60612
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, 44111
Medical City Dallas Hospital
Dallas, Texas, 75230
Cancer Centers of the Carolinas - Eastside
Greenville, South Carolina, 29615
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Cancer Research Center of Hawaii
Honolulu, Hawaii, 96813
Florida Cancer Institute - Bayonet Point
Hudson, Florida, 34667
Holden Comprehensive Cancer Center at University of Iowa
Iowa City, Iowa, 52242-1009
Scripps Cancer Center at Scripps Clinic
La Jolla, California, 92037
David and Donna Long Center for Cancer Treatment at Sharp Grossmont Hospital
La Mesa, California, 91942
Louisiana Oncology Associates - Lafayette
Lafayette, Louisiana, 70506
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Veterans Affairs Medical Center - Long Beach
Long Beach, California, 90822
Joe Arrington Cancer Research and Treatment Center
Lubbock, Texas, 79410-1894
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
Oncology-Hematology Group of South Florida, P.A.
Miami, Florida, 33176
University of Minnesota Cancer Center
Minneapolis, Minnesota, 55455
Stanley S. Scott Cancer Center at Louisiana State University Medical Center - New Orleans
New Orleans, Louisiana, 70112
New York Weill Cornell Cancer Center at Cornell University
New York, New York, 10021
Herbert Irving Comprehensive Cancer Center at Columbia University
New York, New York, 10032
Helen F. Graham Cancer Center
Newark, Delaware, 19713
Ocala Research Institute, Incorporated
Ocala, Florida, 34480
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
Omaha, Nebraska, 68198-7680
Albert Einstein Cancer Center
Philadelphia, Pennsylvania, 19141
California Pacific Medical Center - Pacific Campus
San Francisco, California, 94115
Saint Louis University Cancer Center
St Louis, Missouri, 63110
Siteman Cancer Center at Barnes-Jewish Hospital
St Louis, Missouri, 63110
Olive View - UCLA Medical Center Foundation
Sylmar, California, 91342
SUNY Upstate Medical University Hospital
Syracuse, New York, 13210
Albert Einstein Cancer Center at Albert Einstein College of Medicine
The Bronx, New York, 10467
California Hematology/Oncology Medical Group
Torrance, California, 90505
Arizona Clinical Research Center, Incorporated
Tucson, Arizona, 85715
New York Medical College
Valhalla, New York, 10595
Lombardi Cancer Center at Georgetown University Medical Center
Washington D.C., District of Columbia, 20007
Canada3 sites
Ottawa Hospital Regional Cancer Centre - General Campus
Ottawa, Ontario, K1H 8L6
Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
St. Boniface General Hospital
Winnipeg, Manitoba, R2H 2A6
About this study
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
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.
Read the 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.
- Conditions
- Liver Cancer
- Being tested
- doxorubicin hydrochloride, nolatrexed dihydrochloride
- Keywords
- localized unresectable adult primary liver cancer, advanced adult primary liver cancer, recurrent adult primary liver cancer, adult primary hepatocellular carcinoma
- Medical subject headings
- Liver Neoplasms, Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nolatrexed dihydrochlorideDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival
Secondary outcomes (6)
Time to progression
Time to treatment failure
Response rate (complete response, partial response, stable disease)
Survival probabilities at 3, 6, 9, and 12 months
Safety
Response to treatment in patients with and without prior therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startSep 2000
- Study completionNov 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Liver CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- None (open label)
Sponsor and investigators
- Lead sponsor
- Eximias Pharmaceutical
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Gregory R. Suplick, Study chair, Eximias Pharmaceutical
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00012324
- Sponsor's protocol ID
- ZARIX-ZX101-301
- Other IDs
- CDR0000068506, AG-337-301
- Status last verified
- Oct 2005
- First submitted
- 3 Mar 2001
- Last updated
- 26 Jun 2013
- Results posted
- No
Publications
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.
PubMed 17634485
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00012324
- Acronym / sponsor ID
- ZARIX-ZX101-301
- Conditions
- Liver Cancer
- Keywords
- localized unresectable adult primary liver cancer, advanced adult primary liver cancer, recurrent adult primary liver cancer, adult primary hepatocellular carcinoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Lead sponsor
- Eximias PharmaceuticalIndustry (pharma, biotech, devices)
- Study start
- Sep 2000
- Study completion
- Nov 2005 (actual)
- First posted
- 27 Jan 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| doxorubicin hydrochloride | Drug | – |
| nolatrexed dihydrochloride | Drug | – |
Primary outcome
Overall survival
6 secondary outcomes
Time to progression
Time to treatment failure
Response rate (complete response, partial response, stable disease)
Survival probabilities at 3, 6, 9, and 12 months
Safety
Response to treatment in patients with and without prior therapy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2013.
- Results publication: PubMed 17634485Gish 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gregory R. Suplick study chair
Eximias Pharmaceutical
42 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing doxorubicin hydrochloride and nolatrexed dihydrochloride in people with Liver Cancer, run by Eximias Pharmaceutical at 42 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 42 sites in United States, Canada, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00012324, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2013.