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
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
Drug | Synonyms | Arms |
---|
Afatinib | | Open label |
Paclitaxel | | Open 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
Name | Type | Description | Interventions |
---|
Open label | Other | Afatinib 40 mg/day during Period 1 Afatinib 40 mg/day + Paclitaxel 80mg/kg/3w during Period 2 | |
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 22, 2019