Cancers Harbouring an EGFR Mutation, (Excluding Non-squamous Non- Small Cell Lung Cancer, a Registered Indication), a HER2 Mutation or a HER3 Mutation Clinical Trial
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
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
| Status | Recruiting |
| Enrollment | 87 |
| Est. completion date | December 2022 |
| Est. primary completion date | December 2020 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
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 |
| Country | Name | City | State |
|---|---|---|---|
| Belgium | Institut Jules Bordet | Brussels | |
| Belgium | Les Cliniques Universitaires St Luc | Brussels | |
| Belgium | Universitaire Ziekenhuis Antwerpen | Edegem | |
| Belgium | UZ Gent | Gent | |
| Belgium | CHU Sart-Tilman | Liège |
| Lead Sponsor | Collaborator |
|---|---|
| AZ-VUB |
Belgium,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Response rate | 6 weeks | ||
| Primary | Incidence and intensity of adverse events | 4 weeks | ||
| Secondary | Disease control rate | 6 weeks | ||
| Secondary | Progression free survival | 6 weeks | ||
| Secondary | Overall survival | 6 weeks |