3-AP in Treating Patients With Advanced or Metastatic Solid Tumors
A Phase I and Pharmacokinetic Study of Oral 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone(3-AP,Triapine) in the Treatment of Advanced Solid Tumors
Studieoversigt
Status
Intervention / Behandling
Detaljeret beskrivelse
OBJECTIVES:
I. Determine the safety, tolerability, and toxicity of oral 3-AP in patients with advanced solid tumors.
II. Determine the maximum tolerated dose and recommended phase II dose of this drug in these patients.
III. Determine the oral bioavailability and pharmacokinetics of this drug. IV. Assess tumoral expression of genes involved in response and resistance to 3-AP.
V. Observe and record any tumor response in these patients.
OUTLINE: This is a multicenter, dose-escalation study.
Patients receive a one time dose of 3-AP IV over 2 hours on day -7. Patients then receive oral 3-AP twice daily on days 1-3, 8-10, and 15-17. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of oral 3-AP 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. Blood samples for pharmacokinetic analysis are collected periodically over 8 hours after the IV dose of 3-AP and after the first oral dose of 3-AP during course 1.
After completion of study treatment, patients are followed periodically.
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 1
Kontakter og lokationer
Studiesteder
-
-
California
-
Duarte, California, Forenede Stater, 91010
- City of Hope
-
-
Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Criteria:
- Must be able to swallow
- Histologically confirmed solid tumor
- Advanced or metastatic disease
- Measurable or evaluable disease
- No known active CNS metastases
- ECOG performance status 0-1
- Life expectancy > 3 months
- Progressive disease during >= 1 prior standard therapy OR disease unlikely to respond to any currently available therapies
- Patients with previously treated CNS metastases who have no evidence of new CNS metastases AND are stable for >= 2 months are eligible
- Platelet count >= 100,000/mm^3
- Hemoglobin >= 10 g/dL (transfusions allowed)
- Absolute neutrophil count >= 1,500/mm^3
- ALT and AST =< 2.5 times upper limit of normal (ULN)
- Alkaline phosphatase =< 2.5 times ULN
- Creatinine =< 1.5 mg/dL OR creatinine clearance >= 50 mL/min
- Bilirubin normal
- PT/PTT =< 1.5 times ULN
- FEV1 >= 1.2 L
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception 2 weeks prior to and during study treatment
- No mental deficits and/or psychiatric history that may preclude study treatment
- No active heart disease, including any of the following: myocardial infarction within the past 3 months, symptomatic coronary artery disease or heart block, uncontrolled congestive heart failure
- No moderate to severe compromise of pulmonary function
- No active infection
- No other life-threatening illness
- No active coagulation disorder other than occult blood
- No known positivity for glucose-6-phosphate dehydrogenase (G6PD) deficiency
- Recovered from prior treatment
- Prior gemcitabine allowed
- More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- More than 3 weeks since prior radiotherapy or any other treatment for this cancer
- No prior 3-AP
- No concurrent radiotherapy
- No other concurrent investigational agent
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: N/A
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: Arm I
Patients will receive a 2-hour infusion of 3-AP once in week 1.
Beginning in week 2, they will receive 3-AP by mouth twice a day 3 days a week for 3 weeks.
Treatment with 3-AP by mouth may repeat every 4 weeks for as long as benefit is shown.
|
Given IV and orally
Andre navne:
korrelativ undersøgelse
Andre navne:
Korrelativ undersøgelse
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Maximum tolerated dose of oral 3-AP determined by dose-limiting toxicities graded according to the NCI CTCAE version 3.0
Tidsramme: 28 days
|
28 days
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Serum pharmacokinetics of oral triapine
Tidsramme: Baseline, day 4, and day 8
|
Summary statistics of the pharmacokinetic parameters will be tabulated using the logarithmic scale where appropriate.
The relationship of the AUC to the dose will be assessed by least-square regression analysis.
|
Baseline, day 4, and day 8
|
Samarbejdspartnere og efterforskere
Sponsor
Efterforskere
- Ledende efterforsker: Yun Yen, City of Hope Medical Center
Datoer for undersøgelser
Studer store datoer
Studiestart
Primær færdiggørelse (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- NCI-2009-00139 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- U01CA062505 (U.S. NIH-bevilling/kontrakt)
- PHI-52 (Anden identifikator: City of Hope)
- CDR0000507731
- 7225 (CTEP)
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