Phase I trial to study the effectiveness of sarcosinamide nitrosourea in treating patients
who have metastatic or unresectable solid tumors. Drugs used in chemotherapy use different
ways to stop tumor cells from dividing so they stop growing or die
I. Determine the maximum tolerated dose (MTD) of an oral formulation of SarCNU given on an
every 4th day times three schedule (days 1, 5, 9).
II. Establish an appropriate oral dose of SarCNU for phase II clinical trials. III. Identify
the dose-limiting toxicities (DLTs) of SarCNU. IV. Determine the oral bioavailability of
SarCNU. V. Characterize the plasma pharmacokinetics of SarCNU.
I. Determine whether SarCNU undergoes metabolic N-demethylation to generate reactive
isocyanate species that have been implicated in BCNU pulmonary toxicity.
II. Evaluate response to treatment with SarCNU in patients with measurable or evaluable
III. Attempt to establish pharmacodynamic relationships for response and/or toxicity.
OUTLINE: This is a dose-escalation study.
Patients receive oral sarcosinamide nitrosourea (SarCNU) on days 1, 5, and 9. Treatment
continues every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of SarCNU until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6
patients experience dose-limiting toxicity.
Patients are followed at 4-5 weeks posttreatment.
- Histologically documented malignancy, which is either metastatic or inoperable, for
which there is no known curative or standard palliative therapy, or all standard
therapeutic approaches have failed
- Patients with leukemia or primary CNS malignancies are excluded; patients with
metastatic disease to the CNS, who are not receiving anticonvulsants, including
phenytoin, carbamazepine, phenobarbital, primidone, and felbamate, and who have
reasonable expectation of surviving long enough to receive two cycles of therapy, are
- Life expectancy of 2 months or longer
- ECOG performance status of 0-2
- Pretreatment laboratory data, obtained within 14 days of study entry, must meet the
- ANC >= 1,500 /mm^3
- Platelets >= 100,000 /mm^3
- SGOT =< 2.5-times upper limit of normal
- SGPT =< 2.5-times upper limit of normal
- Total bilirubin =< upper limit of normal
- Creatinine =< 1.5 mg/dl
- Creatinine CL >= 60 ml/min (measured 24hr) if creatinine > 1.5 mg/dl
- DLCO >= 80% predicted
- At least 4 weeks since last receiving radiotherapy or chemotherapy and complete
recovery from previous treatment related toxicity
- No prior treatment with a nitrosourea or with bleomycin
- No enzyme inducing anticonvulsant agents
- At least 2 weeks since major surgery
- Patients must not have uncontrolled serious medical or psychiatric illness
- Women of childbearing potential must not be lactating or pregnant, because of the
proven teratogenicity of other agents of this class; a negative pregnancy test has to
be obtained within 2 weeks of entry; both fertile males and females must use adequate
contraception upon entry into the study
- Patients must have given signed informed consent