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Image Assisted Optimization of Proton Radiation Therapy in Chordomas and Chondrosarcomas (CHIPT)

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ClinicalTrials.gov Identifier: NCT04832620
Recruitment Status : Recruiting
First Posted : April 6, 2021
Last Update Posted : April 6, 2022
Sponsor:
Collaborators:
HollandPTC
Varian Medical Systems
Information provided by (Responsible Party):
Augustinis D.G. Krol, MD PhD, Leiden University Medical Center

Brief 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). 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.


Condition or disease
Bone Neoplasm of Vertebral Column Chordoma Chondrosarcoma Magnetic Resonance Imaging PET-CT Proton Therapy

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Study Type : Observational
Estimated Enrollment : 40 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Defining Optimal Imaging Strategies for Diagnosis, Treatment, and Treatment Evaluation of Chordomas and Chondrosarcomas of the Axial Skeleton
Actual Study Start Date : February 2, 2021
Estimated Primary Completion Date : February 2023
Estimated Study Completion Date : November 2023

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Chordoma




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Rel Enhancement (%) [ Time Frame: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment ]
    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.

  2. Max Enhancement (%) [ Time Frame: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment ]
    MRI perfusion parameter showing difference between peak intensity S1 and S0.

  3. 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 ]
    MRI perfusion parameter showing maximum of all relative enhancements over all dynamics

  4. 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 ]

    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.


  5. 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 ]
    MRI perfusion parameter showing time till contrast agent bolus reaches peak intensity

  6. 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 ]
    MRI perfusion parameter showing maximum slope between T0 and time of peak intensity T1

  7. 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 ]
    MRI perfusion parameter showing maximum slope between time of peak intensity T1 and the end of the measurement

  8. 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 ]
    MRI perfusion parameter showing time between point of maximum wash in rate and maximum wash out rate.

  9. Ktrans [ 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 - transfer constant between blood plasma and Extravascular Extracellular Space (EES), also called vascular permeability

  10. kep [ 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 showing rate between EES and blood plasma (also called Tracer Efflux Rate)

  11. Ve [ 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 showing Extravascular Volume fraction (Leakage space); defined as Ktrans / kep

  12. 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 ]
    MRI permeability and perfusion parameter showing area Under the Curve of all time curves

  13. 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 ]
    MRI diffusion parameters

  14. SUV [ Time Frame: At inclusion and and 11 months following the start date fo proton therapy ]
    Standard uptake value extracted from PET-CT imaging

  15. MTV [ Time Frame: At inclusion and and 11 months following the start date fo proton therapy ]
    Metabolic tumor volume extracted from PET-CT imaging

  16. TLG [ Time Frame: At inclusion and and 11 months following the start date fo proton therapy ]
    Total lesion glycolysis extracted from PET-CT imaging



Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
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.
Criteria

Inclusion Criteria:

  • Histologically diagnosed with primary or recurrent chordoma or chondrosarcoma in the axial skeleton (clivus, spine and sacrum)
  • Accepted for standard proton beam therapy

Exclusion Criteria:

  • 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.
  • Patient is under 50 years of age.
  • Lesion size less than 1cm.
  • Patients with WHO 3 and higher.

Information from the National Library of Medicine

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): NCT04832620


Contacts
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Contact: Stijn Krol, dr. PhD +31624539398 A.D.G.Krol@lumc.nl
Contact: Vesna Miladinovic +31682225869 v.miladinovic@lumc.nl

Locations
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Netherlands
HollandPTC Recruiting
Delft, South Holland, Netherlands, 2629 JH
Contact: Stijn Krol, MD PhD    +31624539398    A.D.G.Krol@lumc.nl   
Contact: Charlotte van der Vos, PhD    +31885011186    c.vander.vos@hollandptc.nl   
Principal Investigator: Stijn Krol, MD PhD         
LUMC Recruiting
Leiden, South Holland, Netherlands, 2333 ZA
Contact: Stijn Krol, MD PhD    +31624539398    A.D.G.Krol@lumc.nl   
Contact: Vesna Miladinovic    +31682225869    v.miladinovic@lumc.nl   
Principal Investigator: Hans Bloem, prof. MD PhD         
Sub-Investigator: Stijn Krol, MD PhD         
Sponsors and Collaborators
Leiden University Medical Center
HollandPTC
Varian Medical Systems
Investigators
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Principal Investigator: Stijn Krol, MD PhD LUMC/HollandPTC
Principal Investigator: Hans Bloem, prof. MD PhD LUMC
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Responsible Party: Augustinis D.G. Krol, MD PhD, Radiation oncologist, Leiden University Medical Center
ClinicalTrials.gov Identifier: NCT04832620    
Other Study ID Numbers: 41335
First Posted: April 6, 2021    Key Record Dates
Last Update Posted: April 6, 2022
Last Verified: April 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Augustinis D.G. Krol, MD PhD, Leiden University Medical Center:
Chordoma
Chondrosarcoma
MRI
PET-CT
Proton therapy
Additional relevant MeSH terms:
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Chondrosarcoma
Chordoma
Bone Neoplasms
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sarcoma
Neoplasms, Germ Cell and Embryonal
Neoplasms by Site
Bone Diseases
Musculoskeletal Diseases