An Explorative Study of Afatinib in the Treatment of Advanced Cancer Carrying an EGFR, a HER2 or a HER3 Mutation

Last updated: January 18, 2019
Sponsor: AZ-VUB
Overall Status: Active - Recruiting

Phase

2

Condition

N/A

Treatment

N/A

Clinical Study ID

NCT03810872
Precision 2 - 1200.264
  • Ages > 18
  • All Genders

Study Summary

Objective(s):To investigate the efficacy and safety of afatinib in EGFR, HER 2 and HER3 mutated cancers, regardless of cancer type, excluding EGFR mutated non-small cell lung cancer.

Methodology:Open label, genomic driven trial (basket trial)

No. of patients total entered:Optimal Simon two stage design for the three genetic driven cohorts: 10 patients will be enrolled per cancer type in the first stage and an additional 19 in the second stage (maximum total 87 patients)

Indication : cancers harbouring an EGFR mutation(excluding non-squamous non- small cell lung cancer, a registered indication), a HER2 mutation or a HER3 mutation

Test product(s) : Afatinib At progression paclitaxel will be added for those patients that have no contra-indications

dose: Starting dose of afatinib at 40 mg/day. Dose increase to 50 mg in the absence of adverse events. Stepwise dose reduction to 30,20, 10 mg/day according to drug-related adverse events.

At progression, addition of paclitaxel 80 mg/m2 weekly 3w/4 to afatinib 40 mg/day .

mode of admin. : Oral for afatinib Intravenous for paclitaxel

Duration of treatment: Continuous treatment until progression or unacceptable adverse events or withdrawal of consent.

At disease progression, add paclitaxel until progression or unacceptable adverse event or withdrawal of consent if no contra-indications.

Criteria for efficacy: Primary Endpoint:

• Response rate (CR+ PR) via RECIST v1.1

Secondary Endpoints:

  • Disease control rate (CR+PR+SD)

  • Progression free survival

  • Overall survival

  • To correlate tumor response with findings on tumor biopsies

  • To investigate resistance mechanisms

  • response rate (CR+ PR) determined by RECIST and progression free survival on the combination therapy of afatinib and paclitaxel

Criteria for safety: Incidence and intensity of adverse events according CTCAE v4.0

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Women and men with locally advanced or metastatic cancers harboring either anactivating EGFR mutation or a HER2 mutation or a HER3 mutation

  • Failure of at least one line of standard systemic therapy

  • No eligibility for other open genomic driven phase I, II or III trial available forthese tumor genotypes

  • ECOG performance status ≤2

  • Patient with a life expectancy >3 months

  • Patients able to provide written informed consent prior to enrollment into theclinical trial.

  • Adequate organ function

Exclusion

Exclusion Criteria:

  • Non squamous non-small cell lung cancer harbouring an EGFR mutation (registeredindication)

  • Chemotherapy, biological therapy or investigational agents within four weeks prior tothe start of study treatment

  • Known hypersensitivity to afatinib or the excipients of any of the trial drugs

  • Prior treatment with afatinib

Study Design

Total Participants: 87
Study Start date:
June 21, 2017
Estimated Completion Date:
December 31, 2022

Connect with a study center

  • Institut Jules Bordet

    Brussels, 1000
    Belgium

    Active - Recruiting

  • Les Cliniques Universitaires St Luc

    Brussels, 1200
    Belgium

    Site Not Available

  • Universitaire Ziekenhuis Antwerpen

    Edegem, 2650
    Belgium

    Site Not Available

  • UZ Gent

    Gent, 9000
    Belgium

    Active - Recruiting

  • CHU Sart-Tilman

    Liège, 4000
    Belgium

    Active - Recruiting

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