Diese Seite wurde automatisch übersetzt und die Genauigkeit der Übersetzung wird nicht garantiert. Bitte wende dich an die englische Version für einen Quelltext.

Azacitidine and Entinostat in Treating Patients With Stage I Non-Small Cell Lung Cancer That Has Been Removed By Surgery

14. Januar 2019 aktualisiert von: National Cancer Institute (NCI)

Randomized Phase II Trial of Adjuvant Combined Epigenetic Therapy With 5-Azacitidine and Entinostat in Resected Stage I Non-small Cell Lung Cancer Versus Standard Care

This study combines the deoxyribonucleic acid (DNA) methyltransferase inhibitor, 5-azacitidine (5-AZA), with an orally bioavailable histone deacetylase inhibitor, entinostat (SNDX-275), for the adjuvant treatment of patients with resected stage I non-small cell lung cancer (NCSLC).

Studienübersicht

Status

Beendet

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

PRIMARY OBJECTIVES:

I. To assess the effect of 5-azacitidine and entinostat on the hazard of 3 year progression-free survival in patients with resected stage I non-small cell lung cancer.

SECONDARY OBJECTIVES:

I. To assess the safety, tolerability and toxicity of entinostat and 5-azacitidine in patients with resected stage I non-small cell lung cancer.

II. To explore the effect of entinostat and 5-azacitidine on median disease-free and overall survival in patients with resected stage I non-small cell lung cancer.

III. To assess the pharmacodynamic effects of 5-azacitidine and entinostat on DNA methylation and gene re-expression in patients with resected stage I NSCLC through analysis of sputum.

IV. To estimate the effect of entinostat and 5-azacitidine on progression free survival comparing patients with N2 lymph nodes categorized as methylated pre-treatment with those who are categorized as unmethylated.

V. To establish factors that predict clinical outcome in patients treated with combination epigenetic therapy by performing genome-wide analyses on pre-treatment tumor DNA.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive azacitidine subcutaneously (SC) on days 1-5 and 8-10 and entinostat orally (PO) once daily (QD) on days 3 and 10. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive standard of care.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Studientyp

Interventionell

Einschreibung (Tatsächlich)

13

Phase

  • Phase 2

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienorte

  • Vereinigte Staaten
    • California
      • Los Angeles, California, Vereinigte Staaten, 90033
        • USC / Norris Comprehensive Cancer Center
    • Florida
      • Tampa, Florida, Vereinigte Staaten, 33612
        • Moffitt Cancer Center
    • Maryland
      • Annapolis, Maryland, Vereinigte Staaten, 21401
        • Anne Arundel Medical Center
      • Baltimore, Maryland, Vereinigte Staaten, 21204
        • Greater Baltimore Medical Center
      • Baltimore, Maryland, Vereinigte Staaten, 21224
        • Johns Hopkins Bayview Medical Center
      • Baltimore, Maryland, Vereinigte Staaten, 21231
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
    • Pennsylvania
      • Pittsburgh, Pennsylvania, Vereinigte Staaten, 15232
        • University of Pittsburgh Cancer Institute
    • Tennessee
      • Nashville, Tennessee, Vereinigte Staaten, 37232
        • Vanderbilt-Ingram Cancer Center
    • Texas
      • Dallas, Texas, Vereinigte Staaten, 75390
        • University of Texas Southwestern Medical Center

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

18 Jahre und älter (Erwachsene, Älterer Erwachsener)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Alle

Beschreibung

Inclusion Criteria:

  • Patients must be status post complete (R0) surgical resection of pathologically-proven NSCLC (stage IA-IB according to AJCC version 7)
  • Patients must be at least 4 weeks out from completion of surgery
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Absolute neutrophil count >= 1,000/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin =< 1.5 X institutional upper limit of normal
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
  • Creatinine =< 1.5 X institutional upper limit of normal
  • The effects of entinostat and 5-azacitidine on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, 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; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Patients must be within 8 weeks of completing surgery
  • Patients who have received prior chemotherapy or radiation for treatment of their current diagnosis of lung cancer
  • Patients with sub-lobar resections (ie: wedge resection or segmentectomy)
  • Patients without mediastinal lymph node specimens from mediastinoscopy or surgery (at least level R4 or 7 for right sided tumors OR at least level 5, 6 or 7 for left sided tumors)
  • Patients may not be receiving any other investigational agents
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to entinostat, 5-azacitidine or other agents used in the study
  • 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
  • Pregnant women are excluded from this study because entinostat and 5-azacitidine are agents with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with entinostat or 5-azacitidine, breastfeeding should be discontinued if the mother is treated on this protocol; these potential risks may also apply to other agents used in this study
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with entinostat or 5-azacitidine; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: Zufällig
  • Interventionsmodell: Parallele Zuordnung
  • Maskierung: Keine (Offenes Etikett)

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Experimental: Arm I (azacitidine, entinostat)
Patients receive azacitidine SC on days 1-5 and 8-10 and entinostat PO QD on days 3 and 10. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Sonstiges: Labor-Biomarker-Analyse
Korrelative Studien
Arzneimittel: Entinostat
PO gegeben
Andere Namen:
  • HDAC-Inhibitor SNDX-275
  • MS 27-275
  • MS-275
  • SNDX-275
Arzneimittel: Azacitidin
SC gegeben
Andere Namen:
  • 5 AZC
  • 5-AC
  • 5-Azacytidin
  • 5-AZC
  • Azacytidin
  • Azacytidin, 5-
  • Ladakamycin
  • Mylosar
  • U-18496
  • Vidaza
Kein Eingriff: Arm II (standard of care)
Patients receive standard of care.

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Disease-free Survival (DFS)
Zeitfenster: 3 years
The DFS hazard rate and 95% confidence interval will be reported. At this time, event time distributions for disease-free survival in the two arms will be estimated with the method of Kaplan and Meier and compared using a stratified Cox-proportional hazards model (stratified for stage IA vs IB) with a two-sided alpha of 10%.
3 years

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Factors That Predict Clinical Outcome in Patients Treated With Combination Epigenetic Therapy in Terms of Epigenomic Data Generated From the Illumina Platform
Zeitfenster: Up to 2 years
The study was terminated early due to poor accrual since the requirement of clinic administration of the 5AZA daily and post-operative patients not wanting 6 months of treatment. For this reason, 13 pts were enrolled and data was not analyzed, for which we are unable to make any conclusions or report results.
Up to 2 years
Median Disease-free Survival
Zeitfenster: Up to 5 years
Determined by the method determined by Kaplan and Meier. Estimated with 95% confidence intervals. Cox proportional hazard modeling will be used for multivariate analysis.
Up to 5 years
Number of Relapses and Deaths Per Total Time of Follow-up Comparing Patients With N2 Lymph Nodes in Terms of Methylated and Unmethylated
Zeitfenster: Up to 5 years
Kaplan Meier curves will be used.
Up to 5 years
Overall Survival
Zeitfenster: Up to 5 years
Determined by the method determined by Kaplan and Meier. Estimated with 95% confidence intervals. Cox proportional hazard modeling will be used for multivariate analysis.
Up to 5 years
Presence of Methylation Patterns
Zeitfenster: Up to 2 years
McNemar's test will be used to compare the change in methylation after treatment in sputum.
Up to 2 years
Toxicities Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0
Zeitfenster: Up to 5 years
Simple descriptive statistics will be utilized to display the data.
Up to 5 years

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

National Cancer Institute (NCI)

Ermittler

  • Hauptermittler: Charles Rudin, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn

1. September 2010

Primärer Abschluss (Tatsächlich)

1. Mai 2013

Studienabschluss (Tatsächlich)

1. Mai 2013

Studienanmeldedaten

Zuerst eingereicht

10. September 2010

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

21. September 2010

Zuerst gepostet (Schätzen)

23. September 2010

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

5. Februar 2019

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

14. Januar 2019

Zuletzt verifiziert

1. Januar 2019

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • NCI-2012-02901 (Registrierungskennung: CTRP (Clinical Trial Reporting Program))
  • P30CA006973 (US NIH Stipendium/Vertrag)
  • NA_00038631
  • J1037 (Andere Kennung: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital)
  • 8311 (Andere Kennung: CTEP)

Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .

Klinische Studien zur Nicht-kleinzelliges Lungenkarzinom im Stadium IA

Klinische Studien zur Labor-Biomarker-Analyse

Suchen Sie nach ähnlichen Studien

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

CROs by country

CROs in Russia

Bedingungen

Seltene Krankheiten

Drogeninterventionen

Nahrungsergänzungsmittel

Sponsor / Mitarbeiter

Standorte

3
Abonnieren