- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT00942266
Vorinostat, Fluorouracil, and Leucovorin Calcium in Treating Patients With Metastatic Colorectal Cancer That Has Not Responded to Previous Treatment
A Randomized Phase II Study of Two Dose-Levels of Vorinostat in Combination With 5-FU and Leucovorin in Patients With Refractory Metastatic Colorectal Cancer
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 2
Kontakter og lokationer
Studiesteder
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New York
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Buffalo, New York, Forenede Stater, 14263
- Roswell Park Cancer Institute
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion
- Patients must have histologically or cytologically confirmed colorectal adenocarcinoma that is metastatic and which has failed standard treatment or for which no standard treatment is available
- Patients should have fluoropyrimidine-refractory disease; radiographic evidence of progression within 4 weeks from the last dose of a fluoropyrimidine-based regimen (at least 6 weeks of fluoropyrimidine-based treatment)
- Patients should have received and progressed on (or proved to be intolerant to) oxaliplatin and irinotecan; progression within 6 months from oxaliplatin-based therapy or irinotecan-based therapy is acceptable for eligibility
- Patients with KRAS wild-type or unknown KRAS status tumors should have progressed on or within 6 months from last cetuximab or panitumumab-based therapy; no prior cetuximab therapy is required for KRAS mutant tumors
- ECOG performance status =< 2
- Life expectancy >= 12 weeks
- Ability to understand and the willingness to sign a written informed consent document
- Ability to swallow pills
- Absolute neutrophil count >= 1,500/uL
- Platelets >= 100,000/uL
- Total bilirubin =< institutional upper limit of normal
- AST(SGOT)/ALT(SGPT) =< 3 x institutional upper limit of normal in the absence of metastatic disease to the liver and =< 5 x institutional upper limit of normal in the setting of metastatic disease to the liver
- Creatinine =< 1.5 x institutional upper limit of normal
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
- Males undergoing study treatment should also agree to adequate measures of contraception (partner contraception and use of condoms or abstinence, or vasectomy)
Exclusion
- Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from significant adverse events due to agents administered more than 3 weeks earlier
- Patients may not be receiving any other investigational agents
- Patients with known brain metastases should be excluded from this clinical trial
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat or other agents used in study
- Greater than Grade 2 neuropathy as defined by CTCAE version 3.0
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Baseline EKG with QTc prolongation that is grade 2 or higher by CTCAE version 3.0
- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with vorinostat
- Patients should not have taken valproic acid or other histone deacetylase inhibitors, for at least 4 weeks prior to enrollment
- Patients with known HIV infection or known active viral hepatitis
- Prior treatment with vorinostat
- Other non-study medications known to increase the QTc interval
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
---|---|
Eksperimentel: Arm I
Patients receive low-dose oral vorinostat once daily on days 1-3, leucovorin calcium IV over 2 hours on day 2, and fluorouracil IV over 46 hours on days 2 and 3. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.
|
Givet IV
Andre navne:
Givet IV
Andre navne:
Korrelativ undersøgelse
Andre navne:
Gives oralt
Andre navne:
|
Eksperimentel: Arm II
Patients receive high-dose oral vorinostat once daily on days 1-3 and leucovorin calcium and fluorouracil as in arm I. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.
|
Givet IV
Andre navne:
Givet IV
Andre navne:
Korrelativ undersøgelse
Andre navne:
Gives oralt
Andre navne:
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Disease Control Rate (Stable Disease or Objective Response)
Tidsramme: At 2 months
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Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
At 2 months
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Median Progression-free Survival
Tidsramme: Every 8 weeks, up to 100 weeks.
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Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
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Every 8 weeks, up to 100 weeks.
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Response Rate
Tidsramme: Every 8 weeks; up to 100 weeks.
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Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
Every 8 weeks; up to 100 weeks.
|
Toxicity
Tidsramme: Daily
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Number of participants with an adverse event. Please refer to the adverse event reporting for more detail. |
Daily
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Overall Survival
Tidsramme: Every 12 weeks
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Every 12 weeks
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Vorinostat Pharmacokinetics
Tidsramme: day 2 (cycle 1)
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Blood samples (5 ml of blood each) will be collected in red-top vacutainers (no anticoagulant) at 0 (pre- vorinostat), 0.5, 1, 2, 3, 4, 6, and 8 hours after the vorinostat dose on the first day of 5-FU infusion on cycle 1 (day 2 of cycle 1).
Mean area under the curve is presented with 95% CI.
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day 2 (cycle 1)
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Fluorouracil Steady-state Pharmacokinetics
Tidsramme: Day 1
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Blood samples will be collected for determination of plasma 5-FU steady state concentration at 6 hours after start of 5-FU continuous infusion.
The mean per treatment arm are presented.
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Day 1
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Samarbejdspartnere og efterforskere
Sponsor
Samarbejdspartnere
Efterforskere
- Ledende efterforsker: Wen Wee MA, MD, Roswell Park Cancer Institute
Datoer for undersøgelser
Studer store datoer
Studiestart
Primær færdiggørelse (Faktiske)
Studieafslutning (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
- Sygdomme i fordøjelsessystemet
- Patologiske processer
- Neoplasmer efter histologisk type
- Neoplasmer
- Neoplasmer efter sted
- Karcinom
- Neoplasmer, kirtel og epitel
- Sygdomsegenskaber
- Gastrointestinale neoplasmer
- Neoplasmer i fordøjelsessystemet
- Gastrointestinale sygdomme
- Tyktarmssygdomme
- Tarmsygdomme
- Intestinale neoplasmer
- Endetarmssygdomme
- Kolorektale neoplasmer
- Tilbagevenden
- Adenocarcinom
- Rektale neoplasmer
- Colon neoplasmer
- Lægemidlers fysiologiske virkninger
- Molekylære mekanismer for farmakologisk virkning
- Enzymhæmmere
- Antimetabolitter, Antineoplastisk
- Antimetabolitter
- Antineoplastiske midler
- Immunsuppressive midler
- Immunologiske faktorer
- Beskyttelsesagenter
- Mikronæringsstoffer
- Vitaminer
- Knogletæthedsbevarende midler
- Calciumregulerende hormoner og midler
- Modgift
- Vitamin B kompleks
- Histon deacetylase hæmmere
- Fluorouracil
- Leucovorin
- Kalk
- Levoleucovorin
- Calcium, diæt
- Vorinostat
Andre undersøgelses-id-numre
- I 142808
- NCI-2009-01523
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