Afatinib in Locally Advanced and Metastatic Chordoma
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ClinicalTrials.gov Identifier: NCT03083678 |
Recruitment Status : Unknown
Verified April 2022 by HansGelderblom, Leiden University Medical Center.
Recruitment status was: Active, not recruiting
First Posted : March 20, 2017
Last Update Posted : April 20, 2022
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Chordoma | Drug: Afatinib | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 43 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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. |
Actual Study Start Date : | June 21, 2018 |
Estimated Primary Completion Date : | July 1, 2023 |
Estimated Study Completion Date : | October 1, 2023 |
Arm | Intervention/treatment |
---|---|
Experimental: Afatinib
Afatinib active treatment.
|
Drug: Afatinib
Afatinib will be given daily in a dose of 40 mg orally in a 4 week cycle until disease progression or patient withdrawal.
Other Name: Giotrif |
- 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.
- 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). ]Time to progression during afatinib treatment (TTP2) divided by time to progression before start of this treatment TTP1 (= growth modulation index)
- 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). ]Toxicity determined by CTCAE v 4.03 criteria
- 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. ]Overall survival from start of afatinib treatment
- Translational research - EGFR pathway analysis in tumor tissue [ Time Frame: From date of inclusion until date of first documented of progression or withdrawal (through study completion, an average of 1 year) ]EGFR status by FISH / immunohistochemistry
- Translational research - Genome sequence analysis of available tumor samples [ Time Frame: From date of inclusion until date of first documented of progression or withdrawal (through study completion, an average of 1 year) ]Genetic mutations by DNA whole genome sequencing of fresh samples
- Translational research - circulating tumor DNA [ Time Frame: 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). ]Circulating chordoma tumor DNA identification by WGS and PCR
- Translational research - circulating exosomes [ Time Frame: Analysis on blood samples to be taken at different time points on cycle 1 day 1, cycle 1 day 15, cycle 3 day 1 and cycle 5 day 1. ]Circulating exosomes identification by PCR
- Pharmacokinetic research [ Time Frame: Analysis on blood samples to be taken at different time points on cycle 1 day 1, cycle 1 day 15, cycle 3 day 1 and cycle 5 day 1. ]Area under the curve
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03083678
Italy | |
Istituto Nazionale dei Tumori: Fondazione IRCCS | |
Milan, Italy | |
Netherlands | |
Leiden University Medical Center | |
Leiden, Netherlands | |
United Kingdom | |
University College London Hospital | |
London, United Kingdom |
Principal Investigator: | AJ Gelderblom, Prof | Leiden University Medical Center |
Responsible Party: | HansGelderblom, Prof. Dr., Leiden University Medical Center |
ClinicalTrials.gov Identifier: | NCT03083678 |
Other Study ID Numbers: |
1200.277 |
First Posted: | March 20, 2017 Key Record Dates |
Last Update Posted: | April 20, 2022 |
Last Verified: | April 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Undecided |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
Product Manufactured in and Exported from the U.S.: | No |
EGFR Afatinib |
Chordoma Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Afatinib |
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