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Erlotinib Hydrochloride in Preventing Cancer in Patients With Precancerous Lesions of the Lung

17 februari 2015 bijgewerkt door: National Cancer Institute (NCI)

A Phase I Study of Erlotinib in Patients With Premalignant Lesions of the Lung

This phase I trial studies the side effects and best dose of erlotinib hydrochloride in preventing cancer in patients with precancerous lesions of the lung. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Studie Overzicht

Toestand

Beëindigd

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

PRIMARY OBJECTIVES:

I. To determine the lowest dose of erlotinib (erlotinib hydrochloride) that will decrease the ratio of phosphorylated to total epidermal growth factor receptor (EGFR) (phosphorylated EGFR [pEGFR]/EGFR) by at least 20% in subjects with premalignant lesions of the lung. This will be accomplished by implementing a dose de-escalation trial of erlotinib (i.e., 75, 50, and 25 or 100 mg by mouth daily for a 3-month period), and determining the pEGFR/EGFR ratio in premalignant lesions of the lung epithelium by immunohistochemistry. Changes in the pEGFR/EGFR ratio will be assessed by comparing the pre-treatment (baseline) ratio to that of the post-treatment (3 month) ratio, measured in paraffin embedded biopsy specimens.

SECONDARY OBJECTIVES:

I. To determine the effect of erlotinib on the following biomarkers of potential biological relevance in paraffin embedded lung biopsies, p-v-akt murine thymoma viral oncogene homolog 1 (Akt), p-mitogen-activated protein kinase 1 (Erk), and marker of proliferation Ki-67 (Ki67).

II. To characterize the toxicity profile of erlotinib in this cohort of subjects.

III. To analyze and model erlotinib's pharmacokinetic/pharmacodynamic (PK/PD) profile. Serial blood samples will be drawn at the beginning and at the end of erlotinib treatment, and pharmacokinetic parameters will be determined. The status of EGFR genotype (and that of others genes linked to erlotinib PK/PD) clinical toxicity, and dose will be examined as possible other influential covariates by comparing them to experimentally measured PK profiles, and PD profiles (in particular, the pEGFR/EGFR ratio). The goal of these studies will be to determine the optimal biologic concentration (OBC) of Erlotinib that is associated with the lowest toxicity and highest effect, for a given subject's pharmacogenomic profile.

OUTLINE:

Patients receive erlotinib hydrochloride orally (PO) once daily (QD) for 90 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

60

Fase

  • Fase 1

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Verenigde Staten
    • Illinois
      • Chicago, Illinois, Verenigde Staten, 60611
        • Northwestern University
      • Chicago, Illinois, Verenigde Staten, 60637
        • University of Chicago Comprehensive Cancer Center
    • Massachusetts
      • Boston, Massachusetts, Verenigde Staten, 02118
        • Boston University School of Medicine
    • New York
      • Buffalo, New York, Verenigde Staten, 14263
        • Roswell Park Cancer Institute

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

40 jaar tot 79 jaar (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion Criteria:

  • Diagnosis of a premalignant lung lesion (metaplasia or dysplasia) on autofluorescent bronchoscopy (AFB) within 1 month
  • Participants must have a >= 10 pack year lifetime smoking history; current and former smokers only are eligible for this trial
  • No contraindications for treatment with erlotinib or additional bronchoscopies
  • Absolute neutrophil count (ANC) of >= 1.5 x 10^9/L
  • Platelet count of >= 100 x 10^9/L
  • Creatinine level of less than 1.5 mg/dL
  • Total bilirubin =< 2.0 mg/dl
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 1.5 x upper limit of normal (ULN)
  • Alkaline phosphatase =< 2.5 x ULN
  • Must meet Eastern Cooperative Oncology Group (ECOG) performance status criteria of 0-1
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) throughout the duration of the study and for 1 month following cessation of study drug; females must begin adequate contraception immediately following screening pregnancy test; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately; if she is pregnant, she will be immediately withdrawn from the study
  • Ability to understand and the willingness to sign a written institutional review board (IRB) approved informed consent document

Exclusion Criteria:

  • Subjects with life-threatening medical conditions that would preclude the treatment intervention and bronchoscopy, including, but not limited to, unstable pulmonary function, acute cardiac failure, which is unstable despite medication use; uncontrolled hypertension; uncontrolled diabetes mellitus; unstable coronary artery disease; acute or chronic liver disease, ongoing or active infection; or psychiatric illness/social situations that would limit compliance with study requirements
  • Participants with evidence of an active cancer or carcinoma in situ, are not eligible
  • Participants currently taking medications that induce or inhibit the cytochrome P450, family 3, subfamily A, polypeptide 4-7 (CYP3A4-7) enzymes
  • Participants may not be receiving any other investigational agents within 3 months
  • Participants taking warfarin
  • History of allergic reactions attributed to erlotinib, a known hypersensitivity to erlotinib, or agents with a similar chemical or biological composition to erlotinib
  • Women who are pregnant or lactating are excluded from the study because based on the proposed mechanism of tyrosine kinase inhibition of erlotinib; erlotinib should be assumed to cause fetal harm when administered to a pregnant woman; there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with erlotinib
  • History of interstitial lung disease (ILD)

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Preventie
  • Toewijzing: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Prevention (erlotinib hydrochloride)
Patients receive erlotinib hydrochloride PO QD for 90 days in the absence of disease progression or unacceptable toxicity.
Geneesmiddel: Erlotinibhydrochloride
Gegeven PO
Andere namen:
  • CP-358.774
Ander: Laboratorium Biomarker Analyse
Correlatieve studies
Ander: Farmacologische studie
Correlatieve studies
Andere namen:
  • farmacologische studies

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Tijdsspanne
Change in the ratio of p-EGFR to total EGFR
Tijdsspanne: Baseline up to 90 days
Baseline up to 90 days

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Change in the expression of p-Akt
Tijdsspanne: Baseline up to 90 days
Analyzed using an analysis-of-variance (ANOVA) on the change from baseline expression level with a factor for dose (75, 50, 25 or 100). All tests will be two-sided and tested at level alpha=0.05. If the overall comparison is significant, pairwise comparisons will be done using straight Bonferroni adjustments.
Baseline up to 90 days
Change in the expression of p-Erk
Tijdsspanne: Baseline up to 90 days
Analyzed using an ANOVA on the change from baseline expression level with a factor for dose (75, 50, 25 or 100). All tests will be two-sided and tested at level alpha=0.05. If the overall comparison is significant, pairwise comparisons will be done using straight Bonferroni adjustments.
Baseline up to 90 days
Change in the expression of Ki67
Tijdsspanne: Baseline up to 90 days
Analyzed using an ANOVA on the change from baseline expression level with a factor for dose (75, 50, 25 or 100). All tests will be two-sided and tested at level alpha=0.05. If the overall comparison is significant, pairwise comparisons will be done using straight Bonferroni adjustments.
Baseline up to 90 days
Incidence of toxicities, graded according to Common Toxicity Criteria, version 3.0
Tijdsspanne: Up to 30 days
Up to 30 days

Andere uitkomstmaten

Uitkomstmaat
Tijdsspanne
PK/PD parameters
Tijdsspanne: Up to 90 days
Up to 90 days
Pharmacogenomic profile
Tijdsspanne: Up to 90 days
Up to 90 days

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

National Cancer Institute (NCI)

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 oktober 2009

Primaire voltooiing (Werkelijk)

1 februari 2012

Studie voltooiing (Werkelijk)

1 juni 2013

Studieregistratiedata

Eerst ingediend

13 november 2009

Eerst ingediend dat voldeed aan de QC-criteria

13 november 2009

Eerst geplaatst (Schatting)

16 november 2009

Updates van studierecords

Laatste update geplaatst (Schatting)

18 februari 2015

Laatste update ingediend die voldeed aan QC-criteria

17 februari 2015

Laatst geverifieerd

1 april 2014

Meer informatie

Termen gerelateerd aan deze studie

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • NCI-2013-00750 (Register-ID: CTRP (Clinical Trial Reporting Program))
  • P30CA060553 (Subsidie/contract van de Amerikaanse NIH)
  • N01CN35157 (Subsidie/contract van de Amerikaanse NIH)
  • RPCI-I-121507
  • NU-NWU08-11-01
  • STU00012618
  • NCI 08-11-01 (Andere identificatie: Northwestern University)
  • NWU08-11-01 (Andere identificatie: DCP)

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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