Sarcosinamide Nitrosourea in Treating Patients With Metastatic or Unresectable Solid Tumors

NCT ID: NCT00004079

Last Updated: 2013-02-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-08-31

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.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (SarCNU)

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.

Group Type: EXPERIMENTAL

SarCNU

Intervention Type: DRUG

Given PO

pharmacological study

Intervention Type: OTHER

Correlative studies

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

SarCNU

Given PO

Intervention Type: DRUG

pharmacological study

Correlative studies

Intervention Type: OTHER

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

pharmacological studies

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joseph Eder

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

99-046

Identifier Type: -

Identifier Source: secondary_id

U01CA062490

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000067290

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2013-00028

Identifier Type: -

Identifier Source: org_study_id