- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT00620295
Bortezomib and Gemcitabine in Treating Older Patients With Advanced Solid Tumors
Phase I Study of Bortezomib and Gemcitabine in Elderly Patients With Solid Tumors (X05227)
RATIONALE: Bortezomib may stop the growth of solid tumors by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with gemcitabine may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib and gemcitabine in treating older patients with advanced solid tumors.
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
OBJECTIVES:
Primary
- To determine the maximum tolerated dose of weekly bortezomib and gemcitabine in treating elderly patients with advanced solid tumors.
Secondary
- To characterize the quantitative and qualitative toxicities of bortezomib and gemcitabine in these patients.
- To obtain preliminary information about the anti-tumor activity of bortezomib and gemcitabine.
- To characterize gemcitabine and metabolite pharmacokinetics in patients receiving concurrent bortezomib therapy.
OUTLINE: This is a phase I dose escalation study of bortezomib and gemcitabine.
Patients receive gemcitabine intravenously (IV) over 30 minutes followed 1 hour later by bortezomib IV over 3-5 seconds on days 1 and 8. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of gemcitabine and bortezomib until the maximum tolerated dose of the combination is determined.
Blood is collected periodically for pharmacokinetic and pharmacogenetic studies.
After completion of study treatment, patients are followed every 3 months for up to 1 year.
Studietype
Registrering (Faktiske)
Fase
- Fase 1
Kontakter og plasseringer
Studiesteder
-
-
Minnesota
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Minneapolis, Minnesota, Forente stater, 55455
- Masonic Cancer Center at University of Minnesota
-
-
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 diagnosis of advanced non-hematologic malignancy, including any of the following:
- Breast cancer
- Lung cancer
- Colon cancer
- Pancreatic cancer
- Head and neck cancer
- Sarcoma
Must have failed or become intolerant to prior standard therapy and is no longer likely to respond to such therapy (for all diseases except pancreatic cancer)
- Pancreatic cancer patients may be enrolled with no prior therapy requirements since gemcitabine is the current standard of care 1st line therapy
- Measurable or nonmeasurable disease
- Concurrent enrollment in the University of Minnesota study "Population Pharmacokinetics and Pharmacogenetics of Gemcitabine in Adult Patients with Solid Tumors" (Human Subjects Code 0508M72989) required
- ECOG performance status of 0-1
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Hemoglobin ≥ 10 g/dL
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- Alkaline phosphatase ≤ 3.0 times ULN (5 times ULN if liver has tumor involvement)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 times ULN (5 times ULN if liver has tumor involvement)
- Calculated or measured creatinine clearance > 30 mL/minute
- Fertile patients must use effective contraception during and for 3 months after study participation
- Recovered from all prior therapy
- Prior systemic chemotherapy, immunotherapy, or biological therapy allowed
- At least 3 months since prior bortezomib and/or gemcitabine
- At least 2 weeks since prior systemic therapy
- At least 3 weeks since prior investigational agents (for reasons other than the treatment of cancer)
- At least 2 weeks since prior radiotherapy
Exclusion Criteria:
- Symptomatic brain metastases
- Serious concomitant medical or psychiatric disorders (e.g., active infection or uncontrolled diabetes) that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study
- Myocardial infarction within the past 6 months
- New York Heart Association (NYHA) Class III or IV heart failure
- Uncontrolled angina
- Severe uncontrolled ventricular arrhythmias
- Electrocardiographic evidence of acute ischemia or active conduction system abnormalities
- Peripheral neuropathy ≥ grade 2
- Known hypersensitivity to bortezomib, boron or mannitol
- Prior radiotherapy to ≥ 25% of the bone marrow
- Prior radiotherapy to the whole pelvis
- Concurrent filgrastim (G-CSF) or other hematologic support during course 1 of study treatment
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 |
|---|---|
|
Eksperimentell: Gemcitabine / Bortezomib
Gemcitabine will be administered as a 30 minute intravenous infusion at the patient's assigned dose on day 1 and day 8 of a 21 day cycle. Bortezomib will be given 1 hour after gemcitabine by IVP over 3 to 5 seconds followed by a standard saline on days 1 and 8 of a 21 day treatment cycle until disease progression or for a maximum of 6 cycles. |
Bortezomib will be given 1 hour after gemcitabine by intravenous pyelogram (IVP) over 3 to 5 seconds followed by a standard saline flush or through a running intravenous (IV) line at the patient's assigned dose (1.0 up to 1.8 mg/m^2) on days 1 and 8 of a 21 day treatment cycle until disease progression or for a maximum of 6 cycles.
Andre navn:
Gemcitabine will be administered as a 30 minute intravenous infusion at the patient's assigned dose (800 up to 1000 mg/m^2) on day 1 and day 8 of a 21 day cycle.
Andre navn:
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Maximum tolerated dose of bortezomib and gemcitabine
Tidsramme: Day 21 (Week 3 - Cycle 1)
|
A minimum of a 3 week period (1 cycle) must be completed by all patients within a dose level before dose escalation to the next level may occur.
A cycle is defined as treatment day 1 and 8 with follow-up through day 21.
|
Day 21 (Week 3 - Cycle 1)
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Toxicity
Tidsramme: 30 Days after Last Treatment
|
Toxicity will be graded using the NCI's Common Terminology Criteria for Adverse Events (CTCAE 3.0)
|
30 Days after Last Treatment
|
|
Disease response as measured by RECIST criteria
Tidsramme: Week 4
|
The best overall response is the best response recorded from the start of treatment until disease progression/recurrence, taking as reference for progressive disease the smallest measurements recorded since the treatment began.
|
Week 4
|
|
Characterization of gemcitabine and metabolite pharmacokinetics (as part of co-enrollment in Population Pharmacokinetics and Pharmacogenetics of Gemcitabine in Adult Patients with Solid Tumors")
Tidsramme: Pre-Dose
|
Pharmacokinetics will be done in conjunction with the dosing day 1 of cycle 1 whenever possible.
|
Pre-Dose
|
Samarbeidspartnere og etterforskere
Studierekorddatoer
Studer hoveddatoer
Studiestart
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
- tilbakevendende brystkreft
- tilbakevendende ikke-småcellet lungekreft
- tilbakevendende småcellet lungekreft
- tilbakevendende prostatakreft
- tilbakevendende tykktarmskreft
- tilbakevendende kreft i bukspyttkjertelen
- eggstokkreft
- tilbakevendende osteosarkom
- recurrent head and neck cancer
- recurrent uterine cancer
- recurrent kidney cancer
Ytterligere relevante MeSH-vilkår
- Sykdommer i fordøyelsessystemet
- Sykdommer i luftveiene
- Neoplasmer etter histologisk type
- Neoplasmer
- Lungesykdommer
- Urologiske neoplasmer
- Urogenitale neoplasmer
- Neoplasmer etter nettsted
- Nyresykdommer
- Urologiske sykdommer
- Adenokarsinom
- Karsinom
- Neoplasmer, kjertel og epitel
- Genitale neoplasmer, kvinnelige
- Sykdommer i det endokrine systemet
- Sykdommer i eggstokkene
- Adnexal sykdommer
- Gonadal lidelser
- Neoplasmer i fordøyelsessystemet
- Neoplasmer i endokrine kjertel
- Genitale neoplasmer, hanner
- Prostata sykdommer
- Neoplasmer i luftveiene
- Thoracale neoplasmer
- Pankreassykdommer
- Nyre-neoplasmer
- Karsinom, nyrecelle
- Neoplasmer i hode og nakke
- Prostatiske neoplasmer
- Lungeneoplasmer
- Neoplasmer i eggstokkene
- Neoplasmer i bukspyttkjertelen
- Fysiologiske effekter av legemidler
- Molekylære mekanismer for farmakologisk virkning
- Anti-infeksjonsmidler
- Antivirale midler
- Enzymhemmere
- Antimetabolitter, antineoplastisk
- Antimetabolitter
- Antineoplastiske midler
- Immunsuppressive midler
- Immunologiske faktorer
- Gemcitabin
- Bortezomib
Andre studie-ID-numre
- CDR0000586510
- UMN-2006LS040 (Annen identifikator: CPRC, University of Minnesota)
- UMN-X05227 (Annen identifikator: Millennium Pharm., Inc.)
- x464 (Annen identifikator: Eli Lilly & Co.)
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