- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT00086970
Ifosfamide With or Without O(6)-Benzylguanine in Treating Patients With Unresectable, Metastatic Solid Tumors
A Phase I Study Of BG In Combination With Ifosfamide For Advanced Solid Tumors
Panoramica dello studio
Stato
Intervento / Trattamento
Descrizione dettagliata
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose of O6-benzylguanine when administered with standard high-dose ifosfamide in patients with unresectable, metastatic solid tumors.
II. Determine whether O6-benzylguanine enhances ifosfamide-mediated myelosuppression in patients treated with this regimen.
III. Determine the relationship between O6-benzylguanine dose and intra-individual variability in the degree of myelosuppression in patients treated with this regimen.
IV. Determine the safety and toxicity of this regimen in these patients.
SECONDARY OBJECTIVES:
I. Determine the effect of O6-benzylguanine on pharmacodynamic endpoints, including apoptosis and DNA damage, in patients treated with this regimen.
II. Determine the pharmacokinetics of O6-benzylguanine and its major metabolite, 8-oxoBG, in patients treated with this regimen.
OUTLINE: This is a randomized, open-label, multicenter, dose-escalation study of O6-benzylguanine.
Course 1: All patients receive high-dose ifosfamide IV continuously over 72 hours on days 1-3.
Course 2: Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients receive high-dose ifosfamide as in course 1.
Arm II: Patients receive a bolus dose of O6-benzylguanine (BG) IV over 1 hour on day 1 followed by BG IV continuously and high-dose ifosfamide IV continuously over 72 hours on days 1-3. Cohorts of 6-12 patients receive escalating doses of BG (administered as a bolus and as a continuous infusion during course 2) until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 or 4 of 12 patients experience dose-limiting toxicity.
Course 3 and all subsequent courses: All patients receive BG (at the MTD determined in course 2, arm II) and high-dose ifosfamide as in course 2, arm II. In all courses, all patients also receive filgrastim (G-CSF) beginning on day 5 and continuing until blood counts recover. In all courses and in both arms, treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 1
Contatti e Sedi
Luoghi di studio
-
-
Illinois
-
Chicago, Illinois, Stati Uniti, 60637-1470
- University of Chicago Comprehensive Cancer Center
-
-
Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Inclusion Criteria:
Histologically confirmed solid tumor
- Unresectable, metastatic disease
- No primary tumors
- Eligible for high-dose ifosfamide-based therapy
- No known brain metastases
- Performance status - ECOG 0-1
- Performance status - Karnofsky 70-100%
- More than 12 weeks
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- AST and ALT ≤ 2.5 times upper limit of normal
- Bilirubin normal
- Creatinine normal
- Creatinine clearance ≥ 60 mL/min
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 4 weeks after study participation
- No history of allergic reaction attributed to compounds of similar chemical or biological composition to O6-benzylguanine or other study agents
- No concurrent uncontrolled illness
- No active or ongoing infection
- No psychiatric illness or social situation that would preclude study compliance
- More than 24 hours since prior colony-stimulating factors (filgrastim [G-CSF] or sargramostim [GM-CSF])
- No prior hematopoietic stem cell transplantation
- No concurrent pegfilgrastim
- No concurrent immunotherapy
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
- No other concurrent chemotherapy
- No concurrent hormonal therapy
- More than 4 weeks since prior radiotherapy and recovered
- No concurrent therapeutic radiotherapy
- More than 4 weeks since prior anticancer therapy
- No more than 2 prior cytotoxic regimens
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No other concurrent anticancer agents or therapies
- No other concurrent investigational agents
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
---|---|
Sperimentale: Arm I (ifosfamide)
Patients receive high-dose ifosfamide IV continuously over 72 hours on days 1-3.
|
Dato IV
Altri nomi:
|
Sperimentale: Arm II (O6-benzylguanine, ifosfamide)
Patients receive a bolus dose of O6-benzylguanine (BG) IV over 1 hour on day 1 followed by BG IV continuously and high-dose ifosfamide IV continuously over 72 hours on days 1-3.
|
Dato IV
Altri nomi:
Dato IV
Altri nomi:
|
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Change in degree of myelosuppression (thrombocytopenia and neutropenia) quantified by both duration of neutropenia and severity of neutropenia
Lasso di tempo: Baseline up to 1 year
|
Baseline up to 1 year
|
|
Maximum tolerated dose (MTD) of O6-benzylguanine defined as the dose preceding that at which 3 of 6 or 4 of 12 patients experience dose-limiting toxicity
Lasso di tempo: 21 days
|
DLT is defined as any >= grade 3 non-hematologic toxicity, grade 4 thrombocytopenia, or prolonged neutropenia.
|
21 days
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Pharmacodynamics including apoptosis and DNA damage
Lasso di tempo: Up to 1 year
|
Up to 1 year
|
|
Pharmacokinetics of O6-benzylguanine
Lasso di tempo: Up to day 3 of course 2
|
Summarized using descriptive statistics (mean, median, standard deviation, and interquartile range).
Estimated via nonlinear regression.
|
Up to day 3 of course 2
|
Collaboratori e investigatori
Sponsor
Investigatori
- Investigatore principale: Sonali Smith, University of Chicago Comprehensive Cancer Center
Studiare le date dei record
Studia le date principali
Inizio studio
Completamento primario (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Stima)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- NCI-2012-02601
- U01CA069852 (Sovvenzione/contratto NIH degli Stati Uniti)
- 12999B
- CDR0000371909 (Identificatore di registro: PDQ (Physician Data Query))
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
Prove cliniche su ifosfamide
-
Polish Lymphoma Research GroupCompletatoLinfoma diffuso a grandi cellule BPolonia