ChordomaPhase 2NCT03083678
Afatinib in Locally Advanced and Metastatic Chordoma
A Phase 2 study testing Afatinib in people with Chordoma, run by Leiden University Medical Center at 3 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chordoma
- What is being tested?
- Afatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 21 Jun 2018to 31 Jan 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
- History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of ≥ 3, unstable angina or poorly controlled arrhythmia as determined by the investigator. Myocardial infarction within 6 months prior to inclusion.
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- 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
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
About this study
Official title: A Phase 2, Single Arm, European Multi-center Trial Evaluating the Efficacy of Afatinib As First-line or Later-line Treatment in Advanced Chordoma.
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
- Being tested
- Afatinib
- Keywords
- EGFR, Afatinib
- Medical subject headings
- Chordoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AfatinibDrug
Also called Giotrif
Afatinib will be given daily in a dose of 40 mg orally in a 4 week cycle until disease progression or patient withdrawal.
| Study group | Role | What they receive |
|---|---|---|
| Afatinib | Experimental | Afatinib active treatment. Receives: Drug: Afatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Time to progression during afatinib treatment (TTP2) divided by time to progression before start of this treatment TTP1 (= growth modulation index)
Measured: 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
Toxicity determined by CTCAE v 4.03 criteria
Measured: From date of start treatment until date of first documented of progression or withdrawal (through study completion, an average of 1 year).
Overall survival.
Overall survival from start of afatinib treatment
Measured: Survival follow-up after end of treatment every 3 months for up to 2 years followed by contact at 3 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2017
- Study start21 Jun 2018
- Primary completion31 Jan 2025
- Study completion31 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ChordomaStudies of the same condition, open and under way.
- More trials run by Leiden University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Chordoma Foundation, Boehringer Ingelheim
- Responsible party
- Principal investigator, HansGelderblom, Leiden University Medical Center
- Investigators
- AJ Gelderblom, Prof, Principal investigator, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03083678
- Sponsor's protocol ID
- 1200.277
- Status last verified
- Feb 2025
- First submitted
- 10 Feb 2017
- Last updated
- 13 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Single Arm, European Multi-center Trial Evaluating the Efficacy of Afatinib As First-line or Later-line Treatment in Advanced Chordoma.
- ClinicalTrials.gov ID
- NCT03083678
- Acronym / sponsor ID
- 1200.277
- Conditions
- Chordoma
- Keywords
- EGFR, Afatinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Collaborators
- Chordoma Foundation, Boehringer Ingelheim
- Study start
- 21 Jun 2018 (actual)
- Primary completion
- 31 Jan 2025 (actual)
- Study completion
- 31 Jan 2025 (actual)
- First posted
- 20 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Afatinib | Experimental | Drug: AfatinibAfatinib active treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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)
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AfatinibAlso: GiotrifAfatinib will be given daily in a dose of 40 mg orally in a 4 week cycle until disease progression or patient withdrawal. | Drug | Afatinib |
Primary outcome
Median PFS according to RECIST 1.1 criteria on afatinib treatment (first-line cohort)
Time frame: From date of start treatment until date of first documented of progression or withdrawal (through study completion, an average of 1 year).
The objective is to increase the median PFS ≥ 12 months in first-line treatment cohort.
Median PFS according to RECIST 1.1 criteria on afatinib treatment (second or later line cohort)
Time frame: From date of start treatment until date of first documented of progression or withdrawal (through study completion, an average of 1 year).
The objective is to increase the median PFS ≥ 9 months in later-line treatment cohort.
Quality of life assessment by EORTC QLC-30 questionnaire.
Time frame: From date of start treatment until date of first documented of progression of withdrawal (through study completion, an average of 1 year).
Change from baseline in EORTC QLC-30 questionnaire score.
Quality of life assessment by Brief pain inventory short form
Time frame: From date of start treatment until date of first documented of progression of withdrawal (through study completion, an average of 1 year).
Change from baseline on Brief pain inventory short form score.
3 secondary outcomes
Growth modulation index.
Time frame: 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
Time frame: From date of start treatment until date of first documented of progression or withdrawal (through study completion, an average of 1 year).
Overall survival.
Time frame: Survival follow-up after end of treatment every 3 months for up to 2 years followed by contact at 3 years.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
AJ Gelderblom, Prof principal investigator
Leiden University Medical Center
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Afatinib in people with Chordoma, run by Leiden University Medical Center at 3 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Italy, Netherlands, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Median PFS according to RECIST 1.1 criteria on afatinib treatment (first-line cohort) (time frame: From date of start treatment until date of first documented of progression or withdrawal (through study completion, an average of 1 year).). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2025.