- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT00042874
Combination Chemotherapy in Treating Patients With Locally Advanced or Metastatic Solid Tumors
An Open-Labeled, Non-Randomized Phase I Study of Alvocidib (Flavopiridol) Administered With Irinotecan (CPT-11) and Fluorouracil/Leucovorin in Patients With Advanced Solid Tumors
Studieoversikt
Status
Detaljert beskrivelse
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose of flavopiridol (alvocidib) when administered with irinotecan hydrochloride, fluorouracil, and leucovorin calcium in patients with locally advanced or metastatic solid tumors.
II. Determine the clinical pharmacokinetics of fluorouracil when administered in this regimen in these patients.
III. Determine, preliminarily, the therapeutic activity of this regimen in these patients.Correlate the role of p21 and Drg1 with apoptosis and treatment response in patients receiving this regimen.
OUTLINE: This is a dose-escalation study of alvocidib and fluorouracil (5-FU).
Patients receive irinotecan hydrochloride IV over 90 minutes followed 5 hours later by leucovorin calcium IV over 2 hours and alvocidib IV over 1 hour immediately followed by 5-FU IV continuously over 48 hours beginning on day 1 of weeks 1, 3, and 5. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of alvocidib and 5-FU 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. Ten additional patients are treated at the MTD.
PROJECTED ACCRUAL: A total of 27-77 patients will be accrued for this study within 11-38 months.
Studietype
Registrering (Faktiske)
Fase
- Fase 1
Kontakter og plasseringer
Studiesteder
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-
New York
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New York, New York, Forente stater, 10065
- Memorial Sloan Kettering Cancer Center
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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 or cytologically confirmed locally advanced or metastatic solid tumor
- Refractory to standard therapy or for which there is no standard therapy
- Preference given to colorectal cancer, upper gastrointestinal cancer, or neuroendocrine tumors
- Evaluable disease
- No CNS metastases or primary CNS malignancy
- Performance status - Karnofsky 60-100%
- WBC at least 3,500/mm^3
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Bilirubin no greater than 1.5 mg/dL
- AST and ALT no greater than 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
- Creatinine no greater than 1.5 mg/dL
- No history of cardiac arrhythmia
- No congestive heart failure
- No myocardial infarction within the past 6 months
- No prior grade 3 or 4 diarrhea secondary to irinotecan, despite optimal antidiarrheal prophylaxis
- HIV negative
- No serious or uncontrolled infection
- No other medical condition or reason that would preclude study participation
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for at least 2 months after study participation
- At least 2 weeks since prior immunotherapy
- No more than 2 prior chemotherapy regimens unless there is no evidence of significant myelotoxicity as determined by the primary investigator
- At least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin)
- Prior irinotecan and fluorouracil allowed
- At least 2 weeks since prior radiotherapy
- Recovered from all prior therapy
- No other concurrent investigational medications
- No concurrent vitamins, antioxidants, or herbal preparations or supplements except a single daily multivitamin
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 |
|---|---|
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Eksperimentell: Treatment (combination chemotherapy)
Patients receive irinotecan hydrochloride IV over 90 minutes followed 5 hours later by leucovorin calcium IV over 2 hours and alvocidib IV over 1 hour immediately followed by 5-FU IV continuously over 48 hours beginning on day 1 of weeks 1, 3, and 5. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of alvocidib and 5-FU 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.
Ten additional patients are treated at the MTD.
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Korrelative studier
Gitt IV
Andre navn:
Gitt IV
Andre navn:
Gitt IV
Andre navn:
Gitt IV
Andre navn:
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
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MTD of biweekly flavopiridol when given in conjunction with irinotecan hydrochloride, fluorouracil, and leucovorin
Tidsramme: 8 weeks
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8 weeks
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Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
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Clinical pharmacokinetics of the regimen under investigation
Tidsramme: Day 1, prior to flavopiridol infusion (t=3:30hr), post flavopiridol infusion (t=4:30hr), prior to flavopiridol infusion (t=3:30hr), post 30 minute flavopiridol bolus (t=4:00), post 4 hour flavopiridol infusion (t=8:00hr)
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Day 1, prior to flavopiridol infusion (t=3:30hr), post flavopiridol infusion (t=4:30hr), prior to flavopiridol infusion (t=3:30hr), post 30 minute flavopiridol bolus (t=4:00), post 4 hour flavopiridol infusion (t=8:00hr)
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Therapeutic activity of flavopiridol in combination with irinotecan hydrochloride in patients with advanced solid tumors
Tidsramme: Up to 7 years
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Up to 7 years
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Change in molecular marker expression
Tidsramme: Baseline to 2 weeks post-treatment
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Baseline to 2 weeks post-treatment
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Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Hovedetterforsker: Gary K. Schwartz, Memorial Sloan Kettering Cancer Center
Studierekorddatoer
Studer hoveddatoer
Studiestart
Primær fullføring (Faktiske)
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
- Neoplasmer
- Fysiologiske effekter av legemidler
- Molekylære mekanismer for farmakologisk virkning
- Enzymhemmere
- Antimetabolitter, antineoplastisk
- Antimetabolitter
- Antineoplastiske midler
- Immunsuppressive midler
- Immunologiske faktorer
- Beskyttende agenter
- Topoisomerasehemmere
- Vekststoffer
- Veksthemmere
- Mikronæringsstoffer
- Proteinkinasehemmere
- Vitaminer
- Kalsiumregulerende hormoner og midler
- Topoisomerase I-hemmere
- Motgift
- Vitamin B kompleks
- Fluorouracil
- Leucovorin
- Irinotekan
- Kalsium
- Levoleucovorin
- Alvocidib
Andre studie-ID-numre
- NCI-2012-01410
- U01CA069856 (U.S. NIH-stipend/kontrakt)
- 5757
- NCI-5757
- CDR0000069479
- MSKCC-02024
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