LymphomaPhase 1NCT00001579
A Phase I Trial of 5-Fluorouracil Given With 776C85 (GW776) and Low-Dose Leucovorin in Adult Patients With Solid Tumors
A Phase 1 study testing 5-Fluorouracil, Ethynyluracil and Leucovorin in people with Lymphoma and Neoplasms, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This is a dose escalation study. During the first period of this study, an initial pharmacological assessment of fluorouracil administered intravenously along with oral leucovorin calcium is made. Leucovorin calcium is given orally bid on days 1-3. Fluorouracil is given as a 24 hour infusion on day 2. Read more about this study
- Who is it for?
- Any age
- What is being tested?
- 5-Fluorouracil, Ethynyluracil and Leucovorin
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 1997to Mar 2001
- Phase
- Phase 1
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
DISEASE CHARACTERISTICS:
Histologically proven solid tumor that has failed standard therapy or for which no such therapy exists.
Tumor may be locally advanced and unresectable, recurrent and/or metastatic.
Lymphomas with minimal or no involvement of bone marrow are also eligible.
No primary malignancies or metastatic disease of the CNS.
No symptomatic pre-existing peripheral neuropathy.
PRIOR/CURRENT THERAPY:
BIOLOGIC THERAPY:
No immunotherapy within past 4 weeks.
Recovered from toxic effects.
CHEMOTHERAPY:
No chemotherapy within past 4 weeks (6 weeks for nitrosoureas).
No mitomycin within past 12 weeks.
Recovered from toxic effects.
ENDOCRINE THERAPY: Not specified.
RADIOTHERAPY:
No radiotherapy within past 2 weeks (8 weeks for strontium therapy).
Recovered from toxic effects.
SURGERY: Recovered from prior surgery.
OTHER: No concurrent cimetidine.
PATIENT CHARACTERISTICS:
AGE: 18 and over.
PERFORMANCE STATUS: ECOG 0-2.
LIFE EXPECTANCY: Not specified.
HEMATOPOIETIC:
Absolute granulocyte count at least 2000/mm(3);
Platelet count at least 100,000/mm(3).
HEPATIC:
Bilirubin no greater than 2 times upper normal limit;
SGOT/SGPT no greater than 4 times upper normal limit.
RENAL:
Creatinine no greater than 1.6 mg/dL;
Creatinine clearance greater than 55 mL/min.
OTHER:
Not pregnant or nursing.
Fertile patients must use effective contraception.
Not HIV positive.
No active infections requiring intravenous antibiotic therapy.
No other serious concurrent illness.
No evidence of hemolytic uremic syndrome.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Cancer Institute (NCI)
Bethesda, Maryland, 20892
About this study
This is a dose escalation study.
During the first period of this study, an initial pharmacological assessment of fluorouracil administered intravenously along with oral leucovorin calcium is made. Leucovorin calcium is given orally bid on days 1-3. Fluorouracil is given as a 24 hour infusion on day 2.
Read more
After a 2 week rest period and resolution of any toxicities experienced during the first period of treatment, patients are given an escalating dose of fluorouracil with fixed doses of leucovorin calcium and ethynyluracil. Ethynyluracil and leucovorin calcium are given bid orally on days 1-3 of each week. Fluorouracil is given bid orally on day 2 of each week. Treatment is repeated for three weeks followed by a one week rest period.
3 to 6 patients are enrolled at each dose level. Dose escalation proceeds until the maximum tolerated dose (MTD) is determined. MTD is defined as the dose preceding that at which 2 or more patients experience dose limiting toxicity.
Read the detailed description
The primary purpose of this Phase I protocol is to develop an orally administered regimen of fluorouracil (5-FU) given with fixed doses of leucovorin (LV) and 776C85 (GW776), a mechanism-based inhibitor of dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme involved in the catabolism of 5-FU. In the presence of 776C85, 5-FU is cleared by renal mechanisms. The schedule employed is intended to mimic the pharmacologic profile associated with a 24 hour weekly continuous infusion of 5-FU without the need for an indwelling central venous catheter. The target population is adult cancer patients with solid tumors.
The first week, each patient will receive a single dose of 5-FU given by 24 hour continuous IV infusion at its recommended Phase II dose with low-dose oral LV. In the third week, the patient will begin 776C85 (GW776) and LV PO on days 1, 2, 3 at fixed doses. Oral 5-FU will be given on day 2, and the dose will be escalated in successive cohorts of patients. Treatment will be repeated weekly for three weeks, followed by a one week break. The dose of 5-FU will be adjusted according to individual tolerance. Cohorts of three patients will be entered at each dose level of 5-FU, which will be escalated until dose-limiting toxicity is seen (guidelines are outlined in the following schema). Treatment will be continued indefinitely until evidence of disease progression, provided the patient is tolerating therapy and wishes to continue.
Biochemical monitoring suggests that there is profound and sustained inhibition of DPD with a single dose of 20 mg PO 776C85 days 1-3 each week for three of four weeks. Once the MTD has been defined for the once daily dosing on days 1, 2, 3 schedule, a simplified schedule will be evaluated in which a single dose of 776C85 on day 1 in the evening, with oral leucovorin days 1 and 2, and 5-FU given day 2 as a single dose.
Since the pharmaceutical company has decided to go with a combined tablet of eniluracil/5-FU for future studies, the new schedule will be oral leucovorin on days 1 \& 2, with 776C85 and 5-FU both given day 2 as a single dose.
- Being tested
- 5-Fluorouracil, Ethynyluracil, Leucovorin
- Keywords
- Biochemical Modulation, Dihydropyrimidine Dehydrogenase, Oral Administration, Pharmacokinetics
- Medical subject headings
- Lymphoma, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-FluorouracilDrug
EthynyluracilDrug
LeucovorinDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2002 (estimated)
- Study startJun 1997
- Study completionMar 2001
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Enrolment
- 50 participants
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001579
- Sponsor's protocol ID
- 970136
- Other IDs
- 97-C-0136
- Status last verified
- May 2000
- First submitted
- 3 Nov 1999
- Last updated
- 17 Jul 2006
- Results posted
- No
Publications
Evans RM, Laskin JD, Hakala MT. Assessment of growth-limiting events caused by 5-fluorouracil in mouse cells and in human cells. Cancer Res. 1980 Nov;40(11):4113-22. No abstract available.
PubMed 6162543Spears CP, Shani J, Shahinian AH, Wolf W, Heidelberger C, Danenberg PV. Assay and time course of 5-fluorouracil incorporation into RNA of L1210/0 ascites cells in vivo. Mol Pharmacol. 1985 Feb;27(2):302-7.
PubMed 2578605Calabro-Jones PM, Byfield JE, Ward JF, Sharp TR. Time-dose relationships for 5-fluorouracil cytotoxicity against human epithelial cancer cells in vitro. Cancer Res. 1982 Nov;42(11):4413-20. No abstract available.
PubMed 7127282
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2006. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of 5-Fluorouracil Given With 776C85 (GW776) and Low-Dose Leucovorin in Adult Patients With Solid Tumors
- ClinicalTrials.gov ID
- NCT00001579
- Acronym / sponsor ID
- 970136
- Keywords
- Biochemical Modulation, Dihydropyrimidine Dehydrogenase, Oral Administration, Pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jun 1997
- Study completion
- Mar 2001
- First posted
- 10 Dec 2002 (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.
This is a dose escalation study.
During the first period of this study, an initial pharmacological assessment of fluorouracil administered intravenously along with oral leucovorin calcium is made. Leucovorin calcium is given orally bid on days 1-3. Fluorouracil is given as a 24 hour infusion on day 2.
After a 2 week rest period and resolution of any toxicities experienced during the first period of treatment, patients are given an escalating dose of fluorouracil with fixed doses of leucovorin calcium and ethynyluracil. Ethynyluracil and leucovorin calcium are given bid orally on days 1-3 of each week. Fluorouracil is given bid orally on day 2 of each week. Treatment is repeated for three weeks followed by a one week rest period.
3 to 6 patients are enrolled at each dose level. Dose escalation proceeds until the maximum tolerated dose (MTD) is determined. MTD is defined as the dose preceding that at which 2 or more patients experience dose limiting toxicity.
Detailed description
The primary purpose of this Phase I protocol is to develop an orally administered regimen of fluorouracil (5-FU) given with fixed doses of leucovorin (LV) and 776C85 (GW776), a mechanism-based inhibitor of dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme involved in the catabolism of 5-FU. In the presence of 776C85, 5-FU is cleared by renal mechanisms. The schedule employed is intended to mimic the pharmacologic profile associated with a 24 hour weekly continuous infusion of 5-FU without the need for an indwelling central venous catheter. The target population is adult cancer patients with solid tumors.
The first week, each patient will receive a single dose of 5-FU given by 24 hour continuous IV infusion at its recommended Phase II dose with low-dose oral LV. In the third week, the patient will begin 776C85 (GW776) and LV PO on days 1, 2, 3 at fixed doses. Oral 5-FU will be given on day 2, and the dose will be escalated in successive cohorts of patients. Treatment will be repeated weekly for three weeks, followed by a one week break. The dose of 5-FU will be adjusted according to individual tolerance. Cohorts of three patients will be entered at each dose level of 5-FU, which will be escalated until dose-limiting toxicity is seen (guidelines are outlined in the following schema). Treatment will be continued indefinitely until evidence of disease progression, provided the patient is tolerating therapy and wishes to continue.
Biochemical monitoring suggests that there is profound and sustained inhibition of DPD with a single dose of 20 mg PO 776C85 days 1-3 each week for three of four weeks. Once the MTD has been defined for the once daily dosing on days 1, 2, 3 schedule, a simplified schedule will be evaluated in which a single dose of 776C85 on day 1 in the evening, with oral leucovorin days 1 and 2, and 5-FU given day 2 as a single dose.
Since the pharmaceutical company has decided to go with a combined tablet of eniluracil/5-FU for future studies, the new schedule will be oral leucovorin on days 1 \& 2, with 776C85 and 5-FU both given day 2 as a single dose.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, 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 |
|---|---|---|
| 5-Fluorouracil | Drug | – |
| Ethynyluracil | Drug | – |
| Leucovorin | Drug | – |
Primary outcome
Not reported in the source record.
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 17 Jul 2006.
- Background: PubMed 6162543Evans RM, Laskin JD, Hakala MT. Assessment of growth-limiting events caused by 5-fluorouracil in mouse cells and in human cells. Cancer Res. 1980 Nov;40(11):4113-22. No abstract available.
- Background: PubMed 2578605Spears CP, Shani J, Shahinian AH, Wolf W, Heidelberger C, Danenberg PV. Assay and time course of 5-fluorouracil incorporation into RNA of L1210/0 ascites cells in vivo. Mol Pharmacol. 1985 Feb;27(2):302-7.
- Background: PubMed 7127282Calabro-Jones PM, Byfield JE, Ward JF, Sharp TR. Time-dose relationships for 5-fluorouracil cytotoxicity against human epithelial cancer cells in vitro. Cancer Res. 1982 Nov;42(11):4413-20. No abstract available.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 5-Fluorouracil, Ethynyluracil and Leucovorin in people with Lymphoma and Neoplasms, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jul 2006. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001579, which also lists 3 linked publications.
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 17 Jul 2006.