Sarcosinamide Nitrosourea in Treating Patients With Metastatic or Unresectable Solid Tumors

A Phase I Trial of Sarcosinamide Nitrosourea (SarCNU) in Patients With Solid Tumors

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

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: pharmacological study; Drug: SarCNU

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.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Other: laboratory biomarker analysis; Correlative studies; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Drug: SarCNU; Given PO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MTD		28 days
Pharmacokinetics: plasma concentration-time profiles of SarCNU	Analyzed by nonlinear least squares regression using WinNonlin (Scientific Consulting, Inc.). Final values of the iterated parameters in the best-fit equations describing the plasma profiles will be used to calculate all pharmacokinetic terms according to standard equations. Mean values of the pharmacokinetic parameters will be calculated at each dose and subject to appropriate statistical tests for the existence of dose-dependent trends.	Days 1 and 9 of course 1: 5, 15, 20, 30, and 45 min; 1, 2, 3, 4, and 6 hr

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Joseph Eder, Dana-Farber Cancer Institute

Study record dates

Study Major Dates

• Study Start: August 1, 1999
• Primary Completion (Actual): September 1, 2005
• Study Completion: December 7, 2022

Study Registration Dates

• First Submitted: December 10, 1999
• First Submitted That Met QC Criteria: April 8, 2003
• First Posted (Estimate): April 9, 2003

Study Record Updates

• Last Update Posted (Estimate): February 1, 2013
• Last Update Submitted That Met QC Criteria: January 31, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: NCI-2013-00028; U01CA062490 (U.S. NIH Grant/Contract); 99-046; CDR0000067290 (Registry Identifier: PDQ (Physician Data Query))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No