NeoplasmPhase 1NCT00001341
A Phase I Trial of ZD1694 (TOMUDEX), an Inhibitor of Thymidylate Synthase, in Pediatric Patients With Advanced Neoplastic Disease
A Phase 1 study testing ZD1694 (TOMUDEX) in people with Neoplasm, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Thymidylate synthase (TS), an enzyme which acts by utilizing 5,10-CH(2)FH(4) in the reductive methylation of deoxyuridylate (dUMP), is required for the de novo synthesis of thymidylate and is a potential chemotherapeutic target. ZD1694 is a new quinazolone folate analog that directly inhibits TS. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Neoplasm
- What is being tested?
- ZD1694 (TOMUDEX)
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 1993to Jun 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 malignancy considered refractory to standard therapy. Objective evidence of progression on prior therapy required.
No leukemia.
Bone marrow involvement by tumor acceptable. Marrow biopsy required if there is a history of involvement or peripheral counts are inadequate.
PRIOR/CONCURRENT THERAPY:
Biologic Therapy: Recovery from toxic effects of prior immunotherapy required.
Chemotherapy: No more than 2 prior chemotherapy regimens and recovered. At least 2 weeks since myelosuppressive therapy (6 weeks since nitrosoureas).
Endocrine Therapy: Not specified.
Radiotherapy:
No prior central axis irradiation (i.e., skull, spine, ribs, pelvis).
Recovery from toxic effects of prior radiotherapy required.
Surgery: Not specified.
Other: No prior bone marrow transplantation.
PATIENT CHARACTERISTICS:
Age: 21 and under.
Performance status: ECOG 0-2.
Life expectancy: At least 8 weeks.
Hematopoietic:
(unless histologic evidence of bone marrow involvement by tumor).
AGC at least 1,500/mm3.
Platelet count at least 100,000/mm3.
Hemoglobin at least 8.0 g/dL.
Prior transfusion acceptable.
Hepatic:
Bilirubin no greater than 2 times normal.
ALT no greater than 2 times normal.
Renal:
Creatinine less than 1.5 mg/dL OR
Creatinine clearance greater than 60 mL/min/1.73 sqm.
Cardiovascular: Not specified.
Pulmonary: Not specified.
OTHER:
No significant accumulation of third space fluid.
No significant systemic illness (e.g., infection).
No pregnant or nursing women.
Pregnancy test required in fertile women.
All patients or their guardians must sign an informed consent.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Cancer Institute (NCI)
Bethesda, Maryland, 20892
About this study
Official title: A Phase I Trial of ZD1694 (TOMUDEX® (Registered Trademark)), an Inhibitor of Thymidylate Synthase, in Pediatric Patients With Advanced Neoplastic Disease
Thymidylate synthase (TS), an enzyme which acts by utilizing 5,10-CH(2)FH(4) in the reductive methylation of deoxyuridylate (dUMP), is required for the de novo synthesis of thymidylate and is a potential chemotherapeutic target. ZD1694 is a new quinazolone folate analog that directly inhibits TS. This phase I trial and pharmacokinetic study will describe and define the toxicities, determine the MTD, and describe the plasma pharmacokinetics of ZD1694 in pediatric patients with refractory cancer. The starting dose for this trial will be 2.0 mg/m(2) administered as a 15 minute IV infusion every 21 days.
Read the detailed description
Thymidylate synthase (TS), an enzyme which acts by utilizing 5,10-CH(2)FH(4) in the reductive methylation of deoxyuridylate (dUMP), is required for the de novo synthesis of thymidylate and is a potential chemotherapeutic target. ZD1694 is a new quinazolone folate analog that directly inhibits TS. This phase I trial and pharmacokinetic study will describe and define the toxicities, determine the MTD, and describe the plasma pharmacokinetics of ZD1694 in pediatric patients with refractory cancer. The starting dose for this trial will be 2.0 mg/m(2) administered as a 15 minute IV infusion every 21 days.
- Conditions
- Neoplasm
- Being tested
- ZD1694 (TOMUDEX)
- Keywords
- Antifolate, Inhibitor, Pharmacokinetics, Thymidylate Synthetase, Toxicity
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZD1694 (TOMUDEX)Drug
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 startSep 1993
- Study completionJun 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 NeoplasmStudies 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
- 60 participants
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001341
- Sponsor's protocol ID
- 930210
- Other IDs
- 93-C-0210
- Status last verified
- Aug 2000
- First submitted
- 3 Nov 1999
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Jackman AL, Taylor GA, Gibson W, Kimbell R, Brown M, Calvert AH, Judson IR, Hughes LR. ICI D1694, a quinazoline antifolate thymidylate synthase inhibitor that is a potent inhibitor of L1210 tumor cell growth in vitro and in vivo: a new agent for clinical study. Cancer Res. 1991 Oct 15;51(20):5579-86.
PubMed 1913676Jackman AL, Marsham PR, Moran RG, Kimbell R, O'Connor BM, Hughes LR, Calvert AH. Thymidylate synthase inhibitors: the in vitro activity of a series of heterocyclic benzoyl ring modified 2-desamino-2-methyl-N10-substituted-5,8-dideazafolates. Adv Enzyme Regul. 1991;31:13-27. doi: 10.1016/0065-2571(91)90006-8.
PubMed 1877386Cunningham D, Zalcberg JR, Rath U, Olver I, Van Cutsem E, Svensson C, Seitz JF, Harper P, Kerr D, Perez-Manga G, et al. 'Tomudex' (ZD1694): results of a randomised trial in advanced colorectal cancer demonstrate efficacy and reduced mucositis and leucopenia. The 'Tomudex' Colorectal Cancer Study Group. Eur J Cancer. 1995 Nov;31A(12):1945-54. doi: 10.1016/0959-8049(95)00502-1.
PubMed 8562146
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of ZD1694 (TOMUDEX® (Registered Trademark)), an Inhibitor of Thymidylate Synthase, in Pediatric Patients With Advanced Neoplastic Disease
- ClinicalTrials.gov ID
- NCT00001341
- Acronym / sponsor ID
- 930210
- Conditions
- Neoplasm
- Keywords
- Antifolate, Inhibitor, Pharmacokinetics, Thymidylate Synthetase, Toxicity
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Sep 1993
- Study completion
- Jun 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.
Thymidylate synthase (TS), an enzyme which acts by utilizing 5,10-CH(2)FH(4) in the reductive methylation of deoxyuridylate (dUMP), is required for the de novo synthesis of thymidylate and is a potential chemotherapeutic target. ZD1694 is a new quinazolone folate analog that directly inhibits TS. This phase I trial and pharmacokinetic study will describe and define the toxicities, determine the MTD, and describe the plasma pharmacokinetics of ZD1694 in pediatric patients with refractory cancer. The starting dose for this trial will be 2.0 mg/m(2) administered as a 15 minute IV infusion every 21 days.
Detailed description
Thymidylate synthase (TS), an enzyme which acts by utilizing 5,10-CH(2)FH(4) in the reductive methylation of deoxyuridylate (dUMP), is required for the de novo synthesis of thymidylate and is a potential chemotherapeutic target. ZD1694 is a new quinazolone folate analog that directly inhibits TS. This phase I trial and pharmacokinetic study will describe and define the toxicities, determine the MTD, and describe the plasma pharmacokinetics of ZD1694 in pediatric patients with refractory cancer. The starting dose for this trial will be 2.0 mg/m(2) administered as a 15 minute IV infusion every 21 days.
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 |
|---|---|---|
| ZD1694 (TOMUDEX) | 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 4 Mar 2008.
- Background: PubMed 1913676Jackman AL, Taylor GA, Gibson W, Kimbell R, Brown M, Calvert AH, Judson IR, Hughes LR. ICI D1694, a quinazoline antifolate thymidylate synthase inhibitor that is a potent inhibitor of L1210 tumor cell growth in vitro and in vivo: a new agent for clinical study. Cancer Res. 1991 Oct 15;51(20):5579-86.
- Background: PubMed 1877386Jackman AL, Marsham PR, Moran RG, Kimbell R, O'Connor BM, Hughes LR, Calvert AH. Thymidylate synthase inhibitors: the in vitro activity of a series of heterocyclic benzoyl ring modified 2-desamino-2-methyl-N10-substituted-5,8-dideazafolates. Adv Enzyme Regul. 1991;31:13-27. doi: 10.1016/0065-2571(91)90006-8.
- Background: PubMed 8562146Cunningham D, Zalcberg JR, Rath U, Olver I, Van Cutsem E, Svensson C, Seitz JF, Harper P, Kerr D, Perez-Manga G, et al. 'Tomudex' (ZD1694): results of a randomised trial in advanced colorectal cancer demonstrate efficacy and reduced mucositis and leucopenia. The 'Tomudex' Colorectal Cancer Study Group. Eur J Cancer. 1995 Nov;31A(12):1945-54. doi: 10.1016/0959-8049(95)00502-1.
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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 ZD1694 (TOMUDEX) in people with Neoplasm, 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 4 Mar 2008. 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 NCT00001341, 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 4 Mar 2008.