Sarcosinamide Nitrosourea in Treating Patients With Metastatic or Unresectable Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00004079
First received: December 10, 1999
Last updated: January 31, 2013
Last verified: January 2013
  Purpose

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


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: SarCNU
Other: pharmacological study
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of Sarcosinamide Nitrosourea (SarCNU) in Patients With Solid Tumors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • MTD [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics: plasma concentration-time profiles of SarCNU [ Time Frame: Days 1 and 9 of course 1: 5, 15, 20, 30, and 45 min; 1, 2, 3, 4, and 6 hr ] [ Designated as safety issue: No ]
    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.


Enrollment: 46
Study Start Date: August 1999
Primary Completion Date: September 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00004079

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Investigators
Principal Investigator: Joseph Eder Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00004079     History of Changes
Other Study ID Numbers: NCI-2013-00028, 99-046, U01CA062490, CDR0000067290
Study First Received: December 10, 1999
Last Updated: January 31, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
2-((((2-chloroethyl)nitrosoamino)carbonyl)amino)propanamide
Carmustine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 26, 2014