Clinical Trials /

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

NCT03810872

Description:

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

Related Conditions:
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: An Explorative Study of Afatinib in the Treatment of Advanced Cancer Carrying an EGFR, a HER2 or a HER3 Mutation
  • Official Title: An Open Explorative Phase II, Open Label Study of Afatinib in the Treatment of Advanced Cancer Carrying an EGFR, a HER2 or a HER3 Mutation

Clinical Trial IDs

  • ORG STUDY ID: Precision 2 - 1200.264
  • NCT ID: NCT03810872

Conditions

  • Cancers Harbouring an EGFR Mutation, (Excluding Non-squamous Non- Small Cell Lung Cancer, a Registered Indication), a HER2 Mutation or a HER3 Mutation

Interventions

DrugSynonymsArms
AfatinibOpen label
PaclitaxelOpen label

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
Open labelOtherAfatinib 40 mg/day during Period 1 Afatinib 40 mg/day + Paclitaxel 80mg/kg/3w during Period 2
  • Afatinib
  • Paclitaxel

Eligibility Criteria

        Inclusion Criteria:

          -  Women and men with locally advanced or metastatic cancers harboring either an
             activating 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 for
             these tumor genotypes

          -  ECOG performance status ≤2

          -  Patient with a life expectancy >3 months

          -  Patients able to provide written informed consent prior to enrollment into the
             clinical trial.

          -  Adequate organ function

        Exclusion Criteria:

          -  Non squamous non-small cell lung cancer harbouring an EGFR mutation (registered
             indication)

          -  Chemotherapy, biological therapy or investigational agents within four weeks prior to
             the start of study treatment

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

          -  Prior treatment with afatinib
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response rate
Time Frame:6 weeks
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Disease control rate
Time Frame:6 weeks
Safety Issue:
Description:
Measure:Progression free survival
Time Frame:6 weeks
Safety Issue:
Description:
Measure:Overall survival
Time Frame:6 weeks
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AZ-VUB

Last Updated

January 18, 2019