An Explorative Study of Afatinib in the Treatment of Advanced Cancer Carrying an EGFR, a HER2 or a HER3 Mutation

NCT03810872 | Unknown Phase 2 DMC

• 1 other identifier: Precision 2 - 1200.264
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 5

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

Conditions

Cancers Harbouring an EGFR Mutation, (Excluding Non-squamous Non- Small Cell Lung Cancer, a Registered Indication), a HER2 Mutation or a HER3 Mutation

Outcome Measures

Primary Outcomes (2)

• Response rate

  6 weeks

• Incidence and intensity of adverse events

  4 weeks

Secondary Outcomes (3)

• Disease control rate

  6 weeks

• Progression free survival

  6 weeks

• Overall survival

  6 weeks

Study Arms (1)

Open label

OTHER

Afatinib 40 mg/day during Period 1 Afatinib 40 mg/day + Paclitaxel 80mg/kg/3w during Period 2

Drug: Afatinib; Drug: Paclitaxel

Interventions

Afatinib DRUG

Open label

Open label

Paclitaxel DRUG

Paclitaxel

Open label

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AZ-VUB: lead

Study Sites (5)

Institut Jules Bordet

Brussels, 1000, Belgium

RECRUITING

Les Cliniques Universitaires St Luc

Brussels, 1200, Belgium

NOT YET RECRUITING

Universitaire Ziekenhuis Antwerpen

Edegem, 2650, Belgium

NOT YET RECRUITING

UZ Gent

Ghent, 9000, Belgium

RECRUITING

CHU Sart-Tilman

Liège, 4000, Belgium

RECRUITING

MeSH Terms

Interventions

Afatinib; Paclitaxel

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Central Study Contacts

Lore Decoster, Dr

CONTACT

+32 2 477 64 15; lore.decoster@uzbrussel.be

Nadia Cappoen

CONTACT

+32 2 477 54 81; nadia.cappoen@uzbrussel.be

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Coordinator Investigator

Study Record Dates

• First Submitted: January 12, 2019
• First Posted: January 22, 2019
• Study Start: June 21, 2017
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2022
• Last Updated: January 22, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

BE (5)