An Explorative Study of Afatinib in the Treatment of Advanced Cancer Carrying an EGFR, a HER2 or a HER3 Mutation
- 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
- Registration Number
- NCT03810872
- Lead Sponsor
- AZ-VUB
- Brief 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 87
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Open label Afatinib Afatinib 40 mg/day during Period 1 Afatinib 40 mg/day + Paclitaxel 80mg/kg/3w during Period 2 Open label Paclitaxel Afatinib 40 mg/day during Period 1 Afatinib 40 mg/day + Paclitaxel 80mg/kg/3w during Period 2
- Primary Outcome Measures
Name Time Method Response rate 6 weeks Incidence and intensity of adverse events 4 weeks
- Secondary Outcome Measures
Name Time Method Disease control rate 6 weeks Progression free survival 6 weeks Overall survival 6 weeks
Trial Locations
- Locations (5)
Les Cliniques Universitaires St Luc
🇧🇪Brussels, Belgium
CHU Sart-Tilman
🇧🇪Liège, Belgium
Institut Jules Bordet
🇧🇪Brussels, Belgium
UZ Gent
🇧🇪Gent, Belgium
Universitaire Ziekenhuis Antwerpen
🇧🇪Edegem, Belgium