An Explorative Study of Afatinib in the Treatment of Advanced Cancer Carrying an EGFR, a HER2 or a HER3 Mutation
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
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
-
Brussels, Belgium, 1000
- Recruiting
- Institut Jules Bordet
-
Principal Investigator:
- Philippe Aftimos, Dr
-
Brussels, Belgium, 1200
- Not yet recruiting
- Les Cliniques Universitaires St Luc
-
Principal Investigator:
- jean-Pascal Machiels, PhD
-
Edegem, Belgium, 2650
- Not yet recruiting
- Universitaire Ziekenhuis Antwerpen
-
Contact:
- Robrecht Lembrechts
- Phone Number: +32 3 821 55 80
- Email: robrecht.lembrechts@uza.be
-
Principal Investigator:
- Christian Rolfo, PhD
-
Gent, Belgium, 9000
- Recruiting
- Uz Gent
-
Principal Investigator:
- Sylvie Rottey, PhD
-
Contact:
- Ann Clue
- Email: ann.clue@uzgent.be
-
Liège, Belgium, 4000
- Recruiting
- CHU Sart-Tilman
-
Principal Investigator:
- Joelle Collignon, Dr
-
Contact:
- Maude Piron
- Phone Number: +32 4 366 82 50
- Email: mpiron@chu.ulg.ac.be
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Other: Open label
Afatinib 40 mg/day during Period 1 Afatinib 40 mg/day + Paclitaxel 80mg/kg/3w during Period 2
|
Paclitaxel
Open label
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Response rate
Time Frame: 6 weeks
|
6 weeks
|
|
Incidence and intensity of adverse events
Time Frame: 4 weeks
|
4 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Progression free survival
Time Frame: 6 weeks
|
6 weeks
|
|
Overall survival
Time Frame: 6 weeks
|
6 weeks
|
|
Disease control rate
Time Frame: 6 weeks
|
6 weeks
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- Precision 2 - 1200.264
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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