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- Klinische proef 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
Studie Overzicht
Toestand
Gedetailleerde beschrijving
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
Inschrijving (Werkelijk)
Fase
- Fase 1
Contacten en locaties
Studie Locaties
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New York
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New York, New York, Verenigde Staten, 10065
- Memorial Sloan Kettering Cancer Center
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
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
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: NVT
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: 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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Correlatieve studies
IV gegeven
Andere namen:
IV gegeven
Andere namen:
IV gegeven
Andere namen:
IV gegeven
Andere namen:
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Tijdsspanne |
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MTD of biweekly flavopiridol when given in conjunction with irinotecan hydrochloride, fluorouracil, and leucovorin
Tijdsspanne: 8 weeks
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8 weeks
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Secundaire uitkomstmaten
Uitkomstmaat |
Tijdsspanne |
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Clinical pharmacokinetics of the regimen under investigation
Tijdsspanne: 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
Tijdsspanne: Up to 7 years
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Up to 7 years
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Change in molecular marker expression
Tijdsspanne: Baseline to 2 weeks post-treatment
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Baseline to 2 weeks post-treatment
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Medewerkers en onderzoekers
Sponsor
Onderzoekers
- Hoofdonderzoeker: Gary K. Schwartz, Memorial Sloan Kettering Cancer Center
Studie record data
Bestudeer belangrijke data
Studie start
Primaire voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Schatting)
Updates van studierecords
Laatste update geplaatst (Schatting)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
- Neoplasmata
- Fysiologische effecten van medicijnen
- Moleculaire mechanismen van farmacologische werking
- Enzymremmers
- Antimetabolieten, antineoplastische
- Antimetabolieten
- Antineoplastische middelen
- Immunosuppressieve middelen
- Immunologische factoren
- Beschermende middelen
- Topoisomeraseremmers
- Groei stoffen
- Groeiremmers
- Micronutriënten
- Proteïnekinaseremmers
- Vitaminen
- Calciumregulerende hormonen en middelen
- Topoisomerase I-remmers
- Tegengif
- Vitamine B-complex
- Fluoruracil
- Leucovorin
- Irinotecan
- Calcium
- Levoleucovorine
- Alvocidib
Andere studie-ID-nummers
- NCI-2012-01410
- U01CA069856 (Subsidie/contract van de Amerikaanse NIH)
- 5757
- NCI-5757
- CDR0000069479
- MSKCC-02024
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