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| Sponsor: | National Cancer Institute (NCI) |
|---|---|
| Information provided by: | National Institutes of Health Clinical Center (CC) |
| ClinicalTrials.gov Identifier: | NCT00001341 |
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Neoplasm |
Drug: ZD1694 (TOMUDEX) |
Phase I |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety Study Primary Purpose: Treatment |
| Official Title: | A Phase I Trial of ZD1694 (TOMUDEX® (Registered Trademark)), an Inhibitor of Thymidylate Synthase, in Pediatric Patients With Advanced Neoplastic Disease |
| Estimated Enrollment: | 60 |
| Study Start Date: | September 1993 |
| Estimated Study Completion Date: | June 2001 |
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.
Eligibility| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations More Information
| ClinicalTrials.gov Identifier: | NCT00001341 History of Changes |
| Other Study ID Numbers: | 930210, 93-C-0210 |
| Study First Received: | November 3, 1999 |
| Last Updated: | March 3, 2008 |
| Health Authority: | United States: Federal Government |
|
Antifolate Inhibitor Pharmacokinetics Thymidylate Synthetase Toxicity |
|
Neoplasms Raltitrexed Folic Acid Antagonists Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
Pharmacologic Actions Antimetabolites, Antineoplastic Antimetabolites Antineoplastic Agents Therapeutic Uses |
