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: Unknown
• Conditions: Cancers Harbouring an EGFR Mutation, (Excluding Non-squamous Non- Small Cell Lung Cancer, a Registered Indication), a HER2 Mutation or a HER3 Mutation
• Intervention / Treatment: Drug: Paclitaxel; Drug: Afatinib

• Study Type: Interventional
• Enrollment (Anticipated): 87
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lore Decoster, Dr; Phone Number: +32 2 477 64 15; Email: lore.decoster@uzbrussel.be
• Study Contact Backup: Name: Nadia Cappoen; Phone Number: +32 2 477 54 81; Email: nadia.cappoen@uzbrussel.be

Study Locations

• Belgium
  • 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: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

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)

Number of Arms

1

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	Drug: Paclitaxel; Paclitaxel; Drug: Afatinib; Open label

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Response rate	6 weeks
Incidence and intensity of adverse events	4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression free survival	6 weeks
Overall survival	6 weeks
Disease control rate	6 weeks

Collaborators and Investigators

• Sponsor: AZ-VUB

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2017
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: January 12, 2019
• First Submitted That Met QC Criteria: January 18, 2019
• First Posted (Actual): January 22, 2019

Study Record Updates

• Last Update Posted (Actual): January 22, 2019
• Last Update Submitted That Met QC Criteria: January 18, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Protein Kinase Inhibitors; Paclitaxel; Afatinib
• Other Study ID Numbers: Precision 2 - 1200.264

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No