Sarcosinamide Nitrosourea in Treating Patients With Metastatic or Unresectable Solid Tumors
A Phase I Trial of Sarcosinamide Nitrosourea (SarCNU) in Patients With Solid Tumors
Studieoversikt
Status
Intervensjon / Behandling
Detaljert beskrivelse
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.
Studietype
Registrering (Faktiske)
Fase
- Fase 1
Kontakter og plasseringer
Studiesteder
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Massachusetts
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Boston, Massachusetts, Forente stater, 02115
- Dana-Farber Cancer Institute
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: 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. |
Korrelative studier
Korrelative studier
Andre navn:
Given PO
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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MTD
Tidsramme: 28 days
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28 days
|
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Pharmacokinetics: plasma concentration-time profiles of SarCNU
Tidsramme: Days 1 and 9 of course 1: 5, 15, 20, 30, and 45 min; 1, 2, 3, 4, and 6 hr
|
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.
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Days 1 and 9 of course 1: 5, 15, 20, 30, and 45 min; 1, 2, 3, 4, and 6 hr
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Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Hovedetterforsker: Joseph Eder, Dana-Farber Cancer Institute
Studierekorddatoer
Studer hoveddatoer
Studiestart
Primær fullføring (Faktiske)
Studiet fullført
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- NCI-2013-00028
- U01CA062490 (U.S. NIH-stipend/kontrakt)
- 99-046
- CDR0000067290 (Registeridentifikator: PDQ (Physician Data Query))
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