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A Phase I Trial of ZD1694 (TOMUDEX® (Registered Trademark)), an Inhibitor of Thymidylate Synthase, in Pediatric Patients With Advanced Neoplastic Disease


Phase 1
N/A
N/A
Not Enrolling
Both
Neoplasm

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Trial Information

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.

Inclusion Criteria


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.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Primary Purpose: Treatment

Authority:

United States: Federal Government

Study ID:

930210

NCT ID:

NCT00001341

Start Date:

September 1993

Completion Date:

June 2001

Related Keywords:

  • Neoplasm
  • Antifolate
  • Inhibitor
  • Pharmacokinetics
  • Thymidylate Synthetase
  • Toxicity
  • Neoplasms

Name

Location

National Cancer Institute (NCI)Bethesda, Maryland  20892