Oxaliplatin and Bortezomib in Treating Patients With Advanced Cancer
A Phase I and Pharmacokinetic Study of Oxaliplatin (Eloxatin™) in Combination With Bortezomib (PS-341, Velcade™) in Patients With Advanced Malignancy
Studienübersicht
Status
Detaillierte Beschreibung
OBJECTIVES:
I. Determine the maximum tolerated dose and recommended phase II dose of oxaliplatin and bortezomib in patients with advanced malignancy.
II. Determine the dose-limiting toxicity of this regimen in these patients. III. Determine the toxicity profile of this regimen in these patients. IV. Determine the antitumor activity of this regimen in these patients. V. Determine the pattern of neurotoxicity and its reversibility in patients responding to prolonged administration of this treatment regimen.
VI. Determine whether the pharmacokinetics and pharmacodynamics of oxaliplatin or bortezomib are altered by the administration of the other agent in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive oxaliplatin IV over 2 hours on days 1 and 15 and bortezomib IV over 3-5 seconds on days 1, 4, 15, and 18. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of oxaliplatin and bortezomib until the maximum tolerated doses (MTDs) are determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Patients are followed for at least 3 months.
PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 4-15 months.
Studientyp
Einschreibung (Tatsächlich)
Phase
- Phase 1
Kontakte und Standorte
Studienorte
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New York
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Bronx, New York, Vereinigte Staaten, 10467-2490
- Montefiore Medical Center
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
Inclusion Criteria:
Histologically confirmed malignancy for which standard curative or palliative measures do not exist or are no longer effective
- Metastatic or unresectable disease
- No known brain metastases
- Performance status - ECOG 0-2
- Performance status - Karnofsky 60-100
- More than 6 months
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Bilirubin normal
- AST and ALT no greater than 5 times upper limit of normal
- Creatinine no greater than 1.5 mg/dL
- 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
- No history of allergic reactions attributed to compounds of similar chemical or biological composition to any platinum or other study agents
- No pre-existing peripheral neuropathy
- No ongoing or active infection
- No psychiatric illness or social situation that would preclude study compliance
- No other concurrent uncontrolled illness
- Prior thalidomide allowed provided patient has no clinical neuropathy
- Prior platinum or antitubulin agents allowed provided patient has no clinical neuropathy
- At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin) and recovered
- More than 3 weeks since prior radiotherapy and recovered
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No other concurrent investigational or commercial agents or therapies for the malignancy
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: N / A
- Interventionsmodell: Einzelgruppenzuweisung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
|
Experimental: Treatment (oxaliplatin, bortezomib)
Patients receive oxaliplatin IV over 2 hours on days 1 and 15 and bortezomib IV over 3-5 seconds on days 1, 4, 15, and 18. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of oxaliplatin and bortezomib until the MTDs are determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. |
Korrelative Studien
Gegeben IV
Andere Namen:
Korrelative Studien
Andere Namen:
Gegeben IV
Andere Namen:
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
|---|---|
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Probability of dose escalation according to true dose limiting toxicity (DLT) rate, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0
Zeitfenster: Up to 28 days
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Up to 28 days
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Area under the curve (AUC) estimates
Zeitfenster: Days 1 and 15 (course 1)
|
Nonlinear compartmental analysis of the oxaliplatin pharmacokinetic data will be performed.
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Days 1 and 15 (course 1)
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Pharmacodynamic assessments (20S proteasome inhibition data)
Zeitfenster: Days 1 and 15 (course 1)
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Summarized by dose and time using standard descriptive statistics.
Asssessments will correlate the AUC in an Emax inhibitory model.
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Days 1 and 15 (course 1)
|
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Sequence of drug administration in terms of PK interaction
Zeitfenster: Days 1 and 15 (course 1)
|
AUC for oxaliplatin and 20-S proteasome inhibition will be calculated and compared for intra-patient variation using paired T-test.
|
Days 1 and 15 (course 1)
|
Mitarbeiter und Ermittler
Sponsor
Ermittler
- Hauptermittler: Howard Hochster, Montefiore Medical Center
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn
Primärer Abschluss (Tatsächlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Schätzen)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Schätzen)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
- NCI-2012-02552
- N01CM62204 (US NIH Stipendium/Vertrag)
- NYU 02-12
- CDR0000316444 (Registrierungskennung: PDQ (Physician Data Query))
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