Bone Neoplasm of Vertebral ColumnCHIPTNCT04832620
Image Assisted Optimization of Proton Radiation Therapy in Chordomas and Chondrosarcomas
An observational study of Bone Neoplasm of Vertebral Column and Chordoma, run by Leiden University Medical Center at 2 sites in Netherlands.
Trial summary
Rationale: Chordomas and chondrosarcomas located in the axial skeleton are malignant neoplasms of bone. These tumors share the same clinical challenges, as the effect of the disease is more a function of their local aggressiveness than their tendency to metastasize (20% metastasize). Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Bone Neoplasm of Vertebral Column, Chordoma, Chondrosarcoma
- How many people
- 40 participants
- Where
- 2 sitesNetherlands
- Study dates
- 2 Feb 2021to Dec 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients referred to HollandPTC, or LUMC, or the Netherlands Committee of Bone tumors, histologically diagnosed with primary or recurrent chordoma or chondrosarcoma in the axial skeleton (clivus, spine and sacrum), and accepted for standard proton beam therapy.
Who may be able to join
- Histologically diagnosed with primary or recurrent chordoma or chondrosarcoma in the axial skeleton (clivus, spine and sacrum)
- Accepted for standard proton beam therapy
Who cannot join
- Diagnosis other than chordoma or chondrosarcoma is made.
- Patient refuses (parts) of the standard treatment protocol.
- Patient refuses MRI due to claustrophobia.
- Patient not suitable for MRI due to the presence of MRI incompatible implants.
- Incapacitated patients.
- Patient doesn't allow coded data to be used for analysis.
Show all 9Show fewer
- Patient is under 50 years of age.
- Lesion size less than 1cm.
- Patients with WHO 3 and higher.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands2 sites, 2 recruiting
- Recruiting
HollandPTC
Delft, South Holland, 2629 JH
Stijn Krol, MD PhD, +31624539398, A.D.G.Krol@lumc.nl
Charlotte van der Vos, PhD, +31885011186, c.vander.vos@hollandptc.nl
- Recruiting
LUMC
Leiden, South Holland, 2333 ZA
Stijn Krol, MD PhD, +31624539398, A.D.G.Krol@lumc.nl
Vesna Miladinovic, +31682225869, v.miladinovic@lumc.nl
About this study
Official title: Defining Optimal Imaging Strategies for Diagnosis, Treatment, and Treatment Evaluation of Chordomas and Chondrosarcomas of the Axial Skeleton
Rationale: Chordomas and chondrosarcomas located in the axial skeleton are malignant neoplasms of bone. These tumors share the same clinical challenges, as the effect of the disease is more a function of their local aggressiveness than their tendency to metastasize (20% metastasize). The local aggressive behavior can cause debilitating morbidity and mortality by destruction of nearby located critical neurovascular structures. Imaging has, in addition to histopathology, a role in diagnosis and in guiding (neo)adjuvant and definitive treatment. Despite the low sensitivity to radiotherapy, proton radiotherapy has been successfully used as an adjunct to resection or as definitive treatment for aggressive chordomas and chondrosarcomas, making it a standard indication for proton therapy in the Netherlands.
Chordomas and chondrosarcomas consist, especially after previous therapy, of non-viable and viable tumor components. Identification of these viable components by functional imaging is important to determine the effect of previous therapy, as change in total tumor volume occurs more than 200 days after change of functional imaging parameters.
Read more
Objective: The main objective of this study is to determine if functional MRI parameters change within 6 months, and earlier than volumetric changes after start of proton beam therapy. This would allow timely differentiation between affected and unaffected (viable) tumor components, which can be used for therapy adjustment.
Secondary objectives: Determine which set of parameters (PET-CT and secondary MRI) can predict clinical outcome (tumor specific mortality, development of metastases, morbidity secondary to tumor activity and morbidity secondary to treatment); determine what type of imaging can accurately identify viable tumor nodules relative to critical anatomical structures; improving understanding of relevance of changing imaging parameters by correlating these with resected tumor.
Study design: Prospective cohort study Study population: LUMC patients diagnosed with primary or recurrent chordoma or chondrosarcoma in the axial skeleton. A number of 20 new patients per year is expected.
Main study parameters: Volumetric and functional MR imaging parameters including permeability parameters.
Secondary parameters are generated by PET-CT (SUV, MTV and TLG), MR (perfusion, permeability and diffusion), therapy (proton beam dose mapping, surgery) and clinical outcome. End points are disease specific survival, progression free survival (including development of metastases), side effects of treatment, and functional outcome (see CRF). In patients who are treated with surgical resection following neo-adjuvant therapy, the surgical specimen will be correlated with imaging findings.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Treatment and clinical management will not be affected in this study, thus the additional burden, risks, and benefits associated with participation in this study are minimal.
Two extra MRI and one PET-CT examination will be planned during proton therapy.
- Conditions
- Bone Neoplasm of Vertebral Column, Chordoma, Chondrosarcoma, Magnetic Resonance Imaging, PET-CT, Proton Therapy
- Keywords
- Chordoma, Chondrosarcoma, MRI, PET-CT, Proton therapy
- Medical subject headings
- Chordoma, Chondrosarcoma
What is being measured
The primary outcome is the main question the study is designed to answer.
Vp(max), Vp(min)
MRI permeability parameter - tumor plasma volume
Measured: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
Secondary outcomes (16)
Rel Enhancement (%)
MRI perfusion parameter showing the signal enhancement of a pixel of certain dynamic relative to that same pixel in the reference dynamic. The reference dynamic is normally the first, pre-contrast dynamic.
Measured: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
Max Enhancement (%)
MRI perfusion parameter showing difference between peak intensity S1 and S0.
Measured: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
Max Rel Enhancement (%)
MRI perfusion parameter showing maximum of all relative enhancements over all dynamics
Measured: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
Time of arrival T0 (s)
MRI perfusion parameter showing time at which the signal intensity increases for at least 20% compared to the baseline (referred to as initial signal intensity S0).
The baseline is the average of the signal intensities of all timepoints before the contrast uptake starts.
Measured: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
Time To Peak (s)
MRI perfusion parameter showing time till contrast agent bolus reaches peak intensity
Measured: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
Wash In Rate (sˉ¹)
MRI perfusion parameter showing maximum slope between T0 and time of peak intensity T1
Measured: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
Wash Out Rate (sˉ¹)
MRI perfusion parameter showing maximum slope between time of peak intensity T1 and the end of the measurement
Measured: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
Brevity of Enhancement (s)
MRI perfusion parameter showing time between point of maximum wash in rate and maximum wash out rate.
Measured: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
Ktrans
MRI permeability parameter - transfer constant between blood plasma and Extravascular Extracellular Space (EES), also called vascular permeability
Measured: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
kep
MRI permeability parameter showing rate between EES and blood plasma (also called Tracer Efflux Rate)
Measured: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
Ve
MRI permeability parameter showing Extravascular Volume fraction (Leakage space); defined as Ktrans / kep
Measured: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
Area under the curve (AUC)
MRI permeability and perfusion parameter showing area Under the Curve of all time curves
Measured: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
mean ADC, Min ADC, Max ADC
MRI diffusion parameters
Measured: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
SUV
Standard uptake value extracted from PET-CT imaging
Measured: At inclusion and and 11 months following the start date fo proton therapy
MTV
Metabolic tumor volume extracted from PET-CT imaging
Measured: At inclusion and and 11 months following the start date fo proton therapy
TLG
Total lesion glycolysis extracted from PET-CT imaging
Measured: At inclusion and and 11 months following the start date fo proton therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2021
- Study start2 Feb 2021
- Primary completionDec 2025 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bone Neoplasm of Vertebral ColumnStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- HollandPTC, Varian Medical Systems
- Responsible party
- Principal investigator, Augustinis D.G. Krol, MD PhD, Leiden University Medical Center
- Investigators
- Stijn Krol, MD PhD, Principal investigator, LUMC/HollandPTCHans Bloem, prof. MD PhD, Principal investigator, LUMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04832620
- Sponsor's protocol ID
- 41335
- Acronym
- CHIPT
- Status last verified
- Nov 2023
- First submitted
- 29 Mar 2021
- Last updated
- 18 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Defining Optimal Imaging Strategies for Diagnosis, Treatment, and Treatment Evaluation of Chordomas and Chondrosarcomas of the Axial Skeleton
- ClinicalTrials.gov ID
- NCT04832620
- Acronym / sponsor ID
- CHIPT / 41335
- Conditions
- Bone Neoplasm of Vertebral Column, Chordoma, Chondrosarcoma, Magnetic Resonance Imaging, PET-CT, Proton Therapy
- Keywords
- Chordoma, Chondrosarcoma, MRI, PET-CT, Proton therapy
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Collaborators
- HollandPTC, Varian Medical Systems
- Study start
- 2 Feb 2021 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 6 Apr 2021 (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.
Rationale: Chordomas and chondrosarcomas located in the axial skeleton are malignant neoplasms of bone. These tumors share the same clinical challenges, as the effect of the disease is more a function of their local aggressiveness than their tendency to metastasize (20% metastasize). The local aggressive behavior can cause debilitating morbidity and mortality by destruction of nearby located critical neurovascular structures. Imaging has, in addition to histopathology, a role in diagnosis and in guiding (neo)adjuvant and definitive treatment. Despite the low sensitivity to radiotherapy, proton radiotherapy has been successfully used as an adjunct to resection or as definitive treatment for aggressive chordomas and chondrosarcomas, making it a standard indication for proton therapy in the Netherlands.
Chordomas and chondrosarcomas consist, especially after previous therapy, of non-viable and viable tumor components. Identification of these viable components by functional imaging is important to determine the effect of previous therapy, as change in total tumor volume occurs more than 200 days after change of functional imaging parameters.
Objective: The main objective of this study is to determine if functional MRI parameters change within 6 months, and earlier than volumetric changes after start of proton beam therapy. This would allow timely differentiation between affected and unaffected (viable) tumor components, which can be used for therapy adjustment.
Secondary objectives: Determine which set of parameters (PET-CT and secondary MRI) can predict clinical outcome (tumor specific mortality, development of metastases, morbidity secondary to tumor activity and morbidity secondary to treatment); determine what type of imaging can accurately identify viable tumor nodules relative to critical anatomical structures; improving understanding of relevance of changing imaging parameters by correlating these with resected tumor.
Study design: Prospective cohort study Study population: LUMC patients diagnosed with primary or recurrent chordoma or chondrosarcoma in the axial skeleton. A number of 20 new patients per year is expected.
Main study parameters: Volumetric and functional MR imaging parameters including permeability parameters.
Secondary parameters are generated by PET-CT (SUV, MTV and TLG), MR (perfusion, permeability and diffusion), therapy (proton beam dose mapping, surgery) and clinical outcome. End points are disease specific survival, progression free survival (including development of metastases), side effects of treatment, and functional outcome (see CRF). In patients who are treated with surgical resection following neo-adjuvant therapy, the surgical specimen will be correlated with imaging findings.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Treatment and clinical management will not be affected in this study, thus the additional burden, risks, and benefits associated with participation in this study are minimal.
Two extra MRI and one PET-CT examination will be planned during proton therapy.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients referred to HollandPTC, or LUMC, or the Netherlands Committee of Bone tumors, histologically diagnosed with primary or recurrent chordoma or chondrosarcoma in the axial skeleton (clivus, spine and sacrum), and accepted for standard proton beam therapy.
Key inclusion criteria (2 listed)
- Histologically diagnosed with primary or recurrent chordoma or chondrosarcoma in the axial skeleton (clivus, spine and sacrum)
- Accepted for standard proton beam therapy
Key exclusion criteria (9 listed)
- Diagnosis other than chordoma or chondrosarcoma is made.
- Patient refuses (parts) of the standard treatment protocol.
- Patient refuses MRI due to claustrophobia.
- Patient not suitable for MRI due to the presence of MRI incompatible implants.
- Incapacitated patients.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Vp(max), Vp(min)
Time frame: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
MRI permeability parameter - tumor plasma volume
16 secondary outcomes
Rel Enhancement (%)
Time frame: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
Max Enhancement (%)
Time frame: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
Max Rel Enhancement (%)
Time frame: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
Time of arrival T0 (s)
Time frame: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
Time To Peak (s)
Time frame: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
Wash In Rate (sˉ¹)
Time frame: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
Wash Out Rate (sˉ¹)
Time frame: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
Brevity of Enhancement (s)
Time frame: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
Ktrans
Time frame: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
kep
Time frame: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
Ve
Time frame: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
Area under the curve (AUC)
Time frame: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
mean ADC, Min ADC, Max ADC
Time frame: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
SUV
Time frame: At inclusion and and 11 months following the start date fo proton therapy
MTV
Time frame: At inclusion and and 11 months following the start date fo proton therapy
TLG
Time frame: At inclusion and and 11 months following the start date fo proton therapy
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2023.
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.
Stijn Krol, MD PhD principal investigator
LUMC/HollandPTC
Hans Bloem, prof. MD PhD principal investigator
LUMC
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Bone Neoplasm of Vertebral Column and Chordoma, run by Leiden University Medical Center at 2 sites in Netherlands.
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 2 inclusion and 9 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: looking for participants now, as of the sponsor's last update on 18 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Stijn Krol, dr. PhD (+31624539398, A.D.G.Krol@lumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Vp(max), Vp(min) (time frame: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment). 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 18 Nov 2023.