Afatinib in Locally Advanced and Metastatic Chordoma

NCT03083678 | Completed Phase 2

• 1 other identifier: 1200.277
• Study Type: interventional
• Target: 43
• Locations: 3 countries
• Sites: 3

Brief Summary

In this phase 2, single arm trial patients with locally advanced or metastatic, pathologically proven, EGFR expressing chordoma will be treated with afatinib. Two cohorts of patients will be included: 20 first line patients and 20 second or further line patients. The treatment will be given in 4 week cycles until disease progression. Median PFS according to RECIST 1.1 will be evaluated. The objective is to increase the median PFS ≥ 12 months in first-line treatment cohort and ≥ 9 months in later-line treatment cohort. Additional exploratory research will be performed, consisting of a pharmacokinetic study and translational studies on EGFR pathway activation and signalling on blood and tumor samples.

Conditions

Chordoma

Keywords

EGFR; Afatinib

Outcome Measures

Primary Outcomes (4)

• Median PFS according to RECIST 1.1 criteria on afatinib treatment (first-line cohort)

  The objective is to increase the median PFS ≥ 12 months in first-line treatment cohort.

  From date of start treatment until date of first documented of progression or withdrawal (through study completion, an average of 1 year).

• Median PFS according to RECIST 1.1 criteria on afatinib treatment (second or later line cohort)

  The objective is to increase the median PFS ≥ 9 months in later-line treatment cohort.

  From date of start treatment until date of first documented of progression or withdrawal (through study completion, an average of 1 year).

• Quality of life assessment by EORTC QLC-30 questionnaire.

  Change from baseline in EORTC QLC-30 questionnaire score.

  From date of start treatment until date of first documented of progression of withdrawal (through study completion, an average of 1 year).

• Quality of life assessment by Brief pain inventory short form

  Change from baseline on Brief pain inventory short form score.

  From date of start treatment until date of first documented of progression of withdrawal (through study completion, an average of 1 year).

Secondary Outcomes (3)

• Growth modulation index.

  From date of start treatment until date of first documented of progression (through study completion, an average of 1 year).

• Toxicity determined by CTCAE v 4.03 criteria

  From date of start treatment until date of first documented of progression or withdrawal (through study completion, an average of 1 year).

• Overall survival.

  Survival follow-up after end of treatment every 3 months for up to 2 years followed by contact at 3 years.

Other Outcomes (5)

• Translational research - EGFR pathway analysis in tumor tissue

  From date of inclusion until date of first documented of progression or withdrawal (through study completion, an average of 1 year)

• Translational research - Genome sequence analysis of available tumor samples

  From date of inclusion until date of first documented of progression or withdrawal (through study completion, an average of 1 year)

• Translational research - circulating tumor DNA

  Analysis on blood samples to be taken at baseline, cycle 4 day 1, cycle 7 day 1 and at end of treatment (within 30 days after last dose of study drug).

Study Arms (1)

Afatinib

EXPERIMENTAL

Afatinib active treatment.

Drug: Afatinib

Interventions

Afatinib DRUG

Afatinib will be given daily in a dose of 40 mg orally in a 4 week cycle until disease progression or patient withdrawal.

Also known as: Giotrif

Afatinib

Eligibility Criteria

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

You may qualify if:

• Locally advanced or metastatic, pathologically proven, EGFR expressing chordoma, not amenable for local therapies
• Patients of 18 years and up
• Documented radiographic progression of disease according to RECIST 1.1 criteria in last 6 months
• ECOG Performance status ≤ 2
• Adequate bone marrow function (Hb ≥ 6.0 mmol/L, absolute neutrophil count ≥ 1.5 x 109/L, platelets ≥ 75 x 109/L)
• An adequate renal function with GFR ≥ 45 ml/min calculated by Cockroft-Gault formula
• Total Bilirubin ≤ 1.5 times upper limit of normal (ULN) (Patients with Gilbert's syndrome total bilirubin must be ≤4 times institutional upper limit of normal).
• Aspartate amino transferase (AST) or alanine amino transferase (ALT) ≤ 3 times ULN (if related to liver metastases ≤ 5 times ULN)
• Ability to swallow medication
• Recovered from any previous therapy related toxicity to ≤ grade 1 at study entry (except for stable sensory neuropathy ≤ grade 2 and alopecia)
• Availability of archival tumor material for central review (if not please obtain a new tumor biopsy)
• Written signed informed consent
• Ability to adhere to the study visits and all protocol requirements

You may not qualify if:

• Life expectancy of less than 3 months
• No measurable lesions according to RECIST 1.1
• Known hypersensitivity to afatinib
• Major surgery less than 4 weeks prior to start of treatment
• Previous treatment with any other investigational agents within 14 days of first day of study drug dosing
• Known pre-existing interstitial lung disease
• Any history or presence of poorly controlled gastrointestinal disorders that could affect the absorption of the study drug (e.g. Crohn's disease, ulcerative colitis, chronic diarrhea, malabsorption)
• Known active hepatitis B infection (defined as presence of HepB sAg and/ or Hep B DNA), active hepatitis C infection (defined as presence of Hep C RNA) and/or known HIV carrier.
• Systemic anti-cancer therapy within 28 days prior to the first dose of study drug , or radiotherapy to an index (or target)lesion within 21 days prior to the first dose of study drug
• Requiring treatment with any of the prohibited concomitant medications listed in Section 6.3.9 that cannot be stopped for the duration of trial participation
• Pregnant or lactating women
• Other invasive malignancies diagnosed within the last 5 years, except non-melanoma skin cancer and localized cured prostate and cervical cancer
• Any history of or concomitant condition that, in the opinion of the Investigator, would compromise the patient's ability to comply with the study or interfere with the evaluation of the efficacy and safety of the test drug

Sponsors & Collaborators

• Leiden University Medical Center: lead
• Chordoma Foundation: collaborator
• Boehringer Ingelheim: collaborator

Study Sites (3)

Istituto Nazionale dei Tumori: Fondazione IRCCS

Milan, Italy

Location

Leiden University Medical Center

Leiden, Netherlands

Location

University College London Hospital

London, United Kingdom

Location

MeSH Terms

Conditions

Chordoma

Interventions

Afatinib

Condition Hierarchy (Ancestors)

Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• AJ Gelderblom, Prof

  Leiden University Medical Center

  PRINCIPAL INVESTIGATOR

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: Prof. Dr.

Study Record Dates

• First Submitted: February 10, 2017
• First Posted: March 20, 2017
• Study Start: June 21, 2018
• Primary Completion: January 31, 2025
• Study Completion: January 31, 2025
• Last Updated: February 13, 2025

Record last verified: 2025-02

Locations

NL (1); IT (1); GB (1)