Description:
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.
Title
- Brief Title: Afatinib in Locally Advanced and Metastatic Chordoma
- 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.
Clinical Trial IDs
- ORG STUDY ID:
1200.277
- NCT ID:
NCT03083678
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Afatinib | Giotrif | Afatinib |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Afatinib | Experimental | Afatinib active treatment. | |
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
- 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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
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). |
Safety Issue: | |
Description: | The objective is to increase the median PFS ≥ 12 months in first-line treatment cohort. |
Secondary Outcome Measures
Measure: | 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). |
Safety Issue: | |
Description: | Time to progression during afatinib treatment (TTP2) divided by time to progression before start of this treatment TTP1 (= growth modulation index) |
Measure: | 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). |
Safety Issue: | |
Description: | Toxicity determined by CTCAE v 4.03 criteria |
Measure: | 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. |
Safety Issue: | |
Description: | Overall survival from start of afatinib treatment |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Leiden University Medical Center |
Trial Keywords
Last Updated
June 9, 2021