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Trial of Continuous Once Daily Oral Treatment Using BIBW 2992 (Afatinib) Plus Sirolimus (Rapamune®) in Patients With Non-small Cell Lung Cancer Harbouring an EGFR Mutation and/or Disease Progression Following Prior Erlotinib or Gefitinib

4 september 2015 bijgewerkt door: Boehringer Ingelheim

A Phase Ib Open Label Clinical Trial of Continuous Once Daily Oral Treatment Using BIBW 2992 Plus Sirolimus in Patients With Non-small Cell Lung Cancer Harbouring an EGFR Mutation and/or Disease Progression Following Prior Erlotinib or Gefitinib

The primary objective of this trial is to identify the Maximum Tolerated Dose of BIBW 2992 therapy when given continuously in combination with Sirolimus.

The MTD will be based on the Dose Limiting Toxicity information collected during the first two cycles.

Overall safety, pharmacokinetics and anti-tumour efficacy will be evaluated as secondary objectives.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Studietype

Ingrijpend

Inschrijving (Werkelijk)

44

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

  • Spanje
      • Badalona (Barcelona), Spanje
        • 1200.70.34001 Boehringer Ingelheim Investigational Site
      • Barcelona, Spanje
        • 1200.70.34008 Boehringer Ingelheim Investigational Site
      • Barcelona, Spanje
        • 1200.70.34009 Boehringer Ingelheim Investigational Site
      • Girona, Spanje
        • 1200.70.34006 Boehringer Ingelheim Investigational Site
      • L'Hospitalet de Llobregat (Barcelona), Spanje
        • 1200.70.34007 Boehringer Ingelheim Investigational Site
      • Majadahonda (Madrid), Spanje
        • 1200.70.34005 Boehringer Ingelheim Investigational Site
      • Valencia, Spanje
        • 1200.70.34004 Boehringer Ingelheim Investigational Site
      • Zaragoza, Spanje
        • 1200.70.34002 Boehringer Ingelheim Investigational Site

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

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion criteria:

  1. Pathologically or cytologically confirmed diagnosis of Stage IIIB or Stage IV NSCLC
  2. Patients who have failed conventional treatment (at least 1 prior treatment line), or for whom no therapy of proven efficacy exists

  3. Patients whose tumors:

    • are EGFR mutation-positive or
    • are EGFR mutation-negative or unknown provided they had disease progression after achieving either response or stable disease for at least 6 months from a previous treatment with erlotinib (Tarceva®) or gefitinib (Iressa®)
  4. Patients aged 18 years or older
  5. Life expectancy of at least three (3) months
  6. Eastern Cooperative Oncology Group (ECOG, R01-0787) performance score 0-2
  7. Written informed consent that is consistent with ICH-GCP guidelines

Exclusion criteria:

  1. Prior major surgery, chemotherapy or radiation therapy within 4 weeks before start of therapy.
  2. Prior treatment with an mTOR inhibitor within the past 4 weeks before start of therapy or concomitantly with this study
  3. Use of erlotinib (Tarceva®) or gefitinib (Iressa®) within 14 days of run-in treatment with Sirolimus
  4. Active CNS metastases (defined as stable for <4 weeks and/or symptomatic and/or requiring treatment with anticonvulsants or steroids)
  5. Severe alteration in serum fasting cholesterol (equal or more than 350 mg/dL) or triglycerides (equal or more than 400 mg/dL). Patients may be allowed to enrol on the trial after initiation of lipid lowering agents.

  6. Requirement for treatment with any of the prohibited concomitant medications:

    • Concomitant CYP3A4 inhibitors within the past 7 days before start of therapy or concomitantly with this study.
    • Concomitant CYP3A4 inducers within the past 14 days before start of therapy or concomitantly with this study.
  7. Any contraindications for therapy with Sirolimus.
  8. Known hypersensitivity to BIBW 2992, Sirolimus or other rapamycin analogues (everolimus, temsirolimus, deforolimus, etc.) or the excipients of any of the trial drugs.
  9. Use of any investigational drug within 4 weeks before start of therapy.

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

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: BIBW 2992 + Sirolimus
Dose escalation of the combination BIBW 2992 plus Sirolimus.
Geneesmiddel: BIBW 2992
Dose escalation (19-40 patients): low or high dose oral + 12 addit. pat. at MTD, until progression or undue AEs
Geneesmiddel: Sirolimus (rapamycin)
Dose escalation (19-40 patients): several dose levels + 12 addit. pat. at MTD until progression or undue AEs.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Occurrence of Dose Limiting Toxicities (DLT)
Tijdsspanne: 2 first cycles, 56 days
Number of participants with of dose limiting toxicities (DLT)
2 first cycles, 56 days

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Best Overall Response
Tijdsspanne: From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days
Best overall response (unconfirmed) according to RECIST v1.1
From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days
Objective Response
Tijdsspanne: From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days
Rate of (unconfirmed) objective response, defined as complete response (CR) or partial response (PR) according to RECIST v1.1
From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days
Rate of Disease Control
Tijdsspanne: From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days
Rate of (unconfirmed) disease control defined as CR, PR, or stable disease (SD), according to RECIST v1.1
From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days
Exploratory Examination of EGFR Mutations (Exons 19, 20 and 21 and Others) in Serum/Plasma DNA and Tumour DNA.
Tijdsspanne: Multiple time points during the trial

Exploratory examination of Epidermal growth factor (receptor)(EGFR) mutations (Exons 19, 20 and 21 and others) in serum/plasma DNA and tumour DNA.

This endpoint was not analysed in the study report as the available data was too limited.
Multiple time points during the trial
Maximum Measured Plasma Concentration of Afatinib at Steady State (Cmax,ss)
Tijdsspanne: 24 hours (h), 311h 55minutes (min), 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h and 336h after first administration of afatinib
Maximum measured plasma concentration of Afatinib at steady state (Cmax,ss)
24 hours (h), 311h 55minutes (min), 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h and 336h after first administration of afatinib
AUC of Afatinib at Steady State Over the Dosing Interval τ (AUCτ,ss)
Tijdsspanne: 24 hours (h), 311h 55minutes (min), 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h and 336h after first administration of afatinib
Area under the curve (AUC) of Afatinib at steady state over the dosing interval τ (AUCτ,ss) for afatinib.
24 hours (h), 311h 55minutes (min), 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h and 336h after first administration of afatinib
Maximum Measured Plasma Concentration of Sirolimus at Steady State (Cmax,ss)
Tijdsspanne: 24 hours (h) 5 minutes (min), 24h, 23h, 22h, 20h, 18h, 16h, 5min before first afatinib administration and 144h, 311h 55min, 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h, 336h, 480h after first administration of afatinib
Maximum measured plasma concentration of sirolimus at steady state (Cmax,ss)
24 hours (h) 5 minutes (min), 24h, 23h, 22h, 20h, 18h, 16h, 5min before first afatinib administration and 144h, 311h 55min, 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h, 336h, 480h after first administration of afatinib
AUC of Sirolimus at Steady State Over the Dosing Interval τ (AUCτ,ss)
Tijdsspanne: 24 hours (h) 5 minutes (min), 24h, 23h, 22h, 20h, 18h, 16h, 5min before first afatinib administration and 144h, 311h 55min, 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h, 336h, 480h after first administration of afatinib
Area under the curve (AUC) of sirolimus at steady state over the dosing interval τ (AUCτ,ss) for afatinib.
24 hours (h) 5 minutes (min), 24h, 23h, 22h, 20h, 18h, 16h, 5min before first afatinib administration and 144h, 311h 55min, 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h, 336h, 480h after first administration of afatinib
Occurrence of Adverse Events According to CTCAE, Version 3.0
Tijdsspanne: From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days
Percentage of participants with adverse events according to highest Common Terminology Criteria for Adverse Events (CTCAE) grade, version 3.0
From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days
Percentage of Patients With Drug-related AEs
Tijdsspanne: From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days
Percentage of patients with drug-related adverse events (AEs).
From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days
Frequency of Patients With Possible Clinically-significant Abnormalities in Liver Enzymes or Total Bilirubin
Tijdsspanne: From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days
Evaluation of laboratory parameters included assessment of the frequency of patients with ALT and AST elevations concurrent with elevated bilirubin and indicative of Hy's law cases.
From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days

Medewerkers en onderzoekers

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

Sponsor

Boehringer Ingelheim

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Nuttige links

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 september 2014

Studie voltooiing (Werkelijk)

1 september 2014

Studieregistratiedata

Eerst ingediend

8 oktober 2009

Eerst ingediend dat voldeed aan de QC-criteria

9 oktober 2009

Eerst geplaatst (Schatting)

12 oktober 2009

Updates van studierecords

Laatste update geplaatst (Schatting)

7 oktober 2015

Laatste update ingediend die voldeed aan QC-criteria

4 september 2015

Laatst geverifieerd

1 september 2015

Meer informatie

Termen gerelateerd aan deze studie

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • 1200.70
  • 2009-010432-18 (EudraCT-nummer: EudraCT)

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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