Alvocidib in Treating Patients With Locally Advanced or Metastatic Solid Tumors
21. februar 2014 oppdatert av: National Cancer Institute (NCI)
A Pilot Study of Flavopiridol in Patients With Advanced Solid Tumors
This phase I trial is studying the side effects and best dose of alvocidib in treating patients with locally advanced or metastatic solid tumors.
Drugs used in chemotherapy, such as alvocidib, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.
Alvocidib may also stimulate the immune system in different ways and stop tumor cells from growing.
It may also stop the growth of solid tumors by blocking blood flow to the tumor.
Studieoversikt
Status
Avsluttet
Intervensjon / Behandling
Detaljert beskrivelse
PRIMARY OBJECTIVES:
I. Determine the toxicity profile and dose-limiting toxicity of flavopiridol (alvocidib) in patients with locally advanced or metastatic solid tumors.
II. Determine the maximum tolerated dose of this drug in these patients.
SECONDARY OBJECTIVES:
I. Determine the pharmacokinetics and pharmacodynamics of this drug in these patients.
II. Determine the immunomodulatory effects of this drug in these patients. III. Determine pharmacogenomics of this drug, using peripheral blood mononuclear cells, in patients who experience clinical response.
OUTLINE: This is a pilot, dose-escalation study.
Patients receive alvocidib intravenously (IV) over 4½ hours once weekly in weeks 1-4. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving stable disease after 4 courses of therapy discontinue study treatment. Patients who achieve complete remission (CR) receive 1 additional course of therapy beyond documentation of CR. Cohorts of 3-6 patients receive escalating doses of alvocidib 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. A total of 10 patients are treated at the MTD.
After completion of study treatment, patients are followed within 4 weeks.
Studietype
Intervensjonell
Registrering (Faktiske)
25
Fase
- Fase 1
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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Ohio
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Columbus, Ohio, Forente stater, 43210
- Ohio State University Medical Center
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år og eldre (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
Inclusion Criteria:
Histologically or cytologically confirmed solid tumor
- Locally advanced or metastatic disease for which curative treatment does not exist or is no longer effective
Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
- No previously irradiated* measurable lesion unless lesion demonstrates progressive disease OR there are other measurable lesions outside the irradiated* field
The following are not considered measurable disease:
- Bone lesions
- Leptomeningeal disease
- Ascites
- Pleural or pericardial effusion
- Lymphangitis cutis/pulmonis
- Abdominal masses that are not confirmed and followed by imaging techniques
- Cystic lesions
- No uncontrolled brain metastases
- Performance status - ECOG 0-1
- At least 6 months
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- AST and ALT ≤ 2.5 times upper limit of normal (ULN)
- Bilirubin ≤ 1.5 times ULN
- Creatinine ≤ 1.5 times ULN
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No uncontrolled cardiac arrhythmia
- No uncontrolled hypertension
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No history of allergic reaction attributed to compounds of similar chemical or biological composition to flavopiridol
- No ongoing or active infection
- No uncontrolled illness
- No psychiatric illness or social situation that would preclude study compliance
- More than 12 weeks since prior hepatic arterial chemoembolization
- More than 4 weeks since prior systemic chemotherapy
- No prior flavopiridol
- See Disease Characteristics
- More than 12 weeks since prior radioactive metaiodobenzylguanidine (MIBG)
- More than 4 weeks since prior external beam radiotherapy
- Recovered from all prior tumor-specific therapy
- More than 4 weeks since prior investigational tumor-specific therapy
- Concurrent octreotide for control of carcinoid syndrome allowed
- No concurrent combination anti-retroviral therapy for HIV-positive patients
- No other concurrent tumor-specific therapy
- No other concurrent investigational therapy
- No other concurrent anticancer therapy
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
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: Treatment (chemotherapy, biological therapy)
Patients receive alvocidib IV over 4½ hours once weekly in weeks 1-4.
Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
|
Korrelative studier
Gitt IV
Andre navn:
Korrelative studier
Andre navn:
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Adverse events of dose escalated alvocidib administered in patients with advanced solid tumors
Tidsramme: At weeks 1-4, 7-10, 11 or 12, and within 4 weeks after the completion of study treatment
|
Graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
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At weeks 1-4, 7-10, 11 or 12, and within 4 weeks after the completion of study treatment
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Pharmacokinetics of alvocidib administered in this schedule
Tidsramme: After the first dose of treatment drug
|
The pharmacokinetic parameters include Cmax, Css, Clearance, t1/2 α, t1/2 β, central volume of distribution and steady state volume of distribution.
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After the first dose of treatment drug
|
|
Immunomodulatory effects of alvocidib
Tidsramme: Baseline, days 1 and 15 of courses 1 and 2, and within 4 weeks after the completion of study treatment
|
Gene expression quantified using Real Time PCR; type 1 and type 2 cytokines, co-stimulatory molecules, and adhesion molecules in PBMCs.
Activation of lymphocyte subsets and presence of co-stimulatory and adhesion molecules assessed using multicolor flow cytometry.
IL-6 levels in plasma will be measured by ELISA.
T-cells will be enriched from PBMCs using mAb-coated immunomagnetic beads and activated with anti-CD3/anti-CD28 mAbs, inomycin or PMA.
Cytokine production will be measured using cytometric bead array.
|
Baseline, days 1 and 15 of courses 1 and 2, and within 4 weeks after the completion of study treatment
|
|
Pharmacogenomics studies on procured PBMCs if clinical responses are observed
Tidsramme: Baseline, and within 4 weeks after the completion of study treatment
|
Performed if clinical responses are observed.
Examine for selected polymorphisms of genes influencing alvocidib metabolism and/or resistance genes that may predict response or toxicity.
These changes will be correlated with AUC, toxicity and clinical response to therapy.
|
Baseline, and within 4 weeks after the completion of study treatment
|
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Measurement of serum tumor markers depending on the tumor type
Tidsramme: Baseline, week 11 or 12, and within 4 weeks after the completion of study treatment
|
Markers include CEA, CA 19-9, CA 15-3, PSA, LDH, AFP, b-HCG, pancreastatin, gastrin, pancreatic polypeptide, glucagon, substance-P, neurotensin, calcitonin, somatostatin, vasoactive intestinal peptide, gastrin releasing polypeptide, ACTH, and chromogranin-A.
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Baseline, week 11 or 12, and within 4 weeks after the completion of study treatment
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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Etterforskere
- Hovedetterforsker: Manisha Shah, Ohio State University
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
1. februar 2006
Primær fullføring (Faktiske)
1. juli 2012
Datoer for studieregistrering
Først innsendt
2. juni 2005
Først innsendt som oppfylte QC-kriteriene
2. juni 2005
Først lagt ut (Anslag)
3. juni 2005
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
24. februar 2014
Siste oppdatering sendt inn som oppfylte QC-kriteriene
21. februar 2014
Sist bekreftet
1. november 2011
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- NCI-2009-00135 (Registeridentifikator: CTRP (Clinical Trial Reporting Program))
- P30CA016058 (U.S. NIH-stipend/kontrakt)
- U01CA076576 (U.S. NIH-stipend/kontrakt)
- OSU-2005C0009
- CDR0000429582
- NCI-7204
- OSU-04111
- OSU 04111 (Annen identifikator: Ohio State University Medical Center)
- 7204 (CTEP)
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