Clinical trial NCT03810872: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Cancers Harbouring an EGFR Mutation, (Excluding Non-squamous Non- Small Cell Lung Cancer, a Registered Indication), a HER2 Mutation or a HER3 Mutation
Lead sponsor: AZ-VUB
Sponsor class: OTHER
First posted: 2019-01-22
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: Response rate
timeFrame: 6 weeks
measure: Incidence and intensity of adverse events
timeFrame: 4 weeks
Secondary outcomes:
measure: Disease control rate
timeFrame: 6 weeks
measure: Progression free survival
timeFrame: 6 weeks
measure: Overall survival
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Brussels
country: Belgium
facility: Les Cliniques Universitaires St Luc
city: Edegem
country: Belgium
facility: Universitaire Ziekenhuis Antwerpen
city: Gent
country: Belgium
facility: UZ Gent
city: Liège
country: Belgium
facility: CHU Sart-Tilman
Study officials:
References: