Clinical trial NCT00004079: Sarcosinamide Nitrosourea in Treating Patients With Metastatic or Unresectable Solid Tumors
Official title: A Phase I Trial of Sarcosinamide Nitrosourea (SarCNU) in Patients With Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Unspecified Adult Solid Tumor, Protocol Specific
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-04-09
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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 disease.

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.

Eligibility criteria: Inclusion Criteria:

* 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 eligible
* 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 following criteria:
* 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

Primary outcomes:
measure: MTD
timeFrame: 28 days
measure: Pharmacokinetics: plasma concentration-time profiles of SarCNU
timeFrame: Days 1 and 9 of course 1: 5, 15, 20, 30, and 45 min; 1, 2, 3, 4, and 6 hr
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Joseph Eder
role: PRINCIPAL_INVESTIGATOR
References: