Exploration of Personalized Biomarkers During Neoadjuvant Radiation Therapy for Spinal and Sacral Chordoma (Canon)

In this study the investigators will study the effects of neoadjuvant radiation therapy (RT), in the form of either proton therapy or stereotactic body radiation therapy (SBRT), on the Circulating tumor DNA (ctDNA), radiographic changes and radiomics, and the validity of these findings will be compared using the current gold standard- pathologic findings. The purpose of this work is to explore whether the biomarkers may be used diagnostically to better understand radiographic changes following RT. The investigators hypothesize that ctDNA levels in combination with imaging biomarkers identified through radiomics will be a sensitive and specific tool for predicting histopathologic response to RT.

Study Overview

• Status: Recruiting
• Conditions: Chordoma of Sacrum; Chordoma of Spine; Chordoma of Skull Base
• Intervention / Treatment: Diagnostic test: ctDNA

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Kristin Redmond, MD, MPH; Phone Number: 4106141642; Email: kjanson3@jhmi.edu
• Study Contact Backup: Name: Jasmine Brooks, BA; Phone Number: 6673068335; Email: jbrook54@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 212887
      • Recruiting
      • Johns Hopkins Hospital
      • Contact: Kristin Redmond, MD; Phone Number: 410-955-6980; Email: kjanson3@jhmi.edu
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
      • Contact: James Schuster, MD, PhD; Phone Number: 215-294-9494; Email: james.schuster@pennmedicine.upenn.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Potential participants who are clinical patients of the PI or co-investigators may be identified during chart review in advance of a routine clinic visit or during a routine clinic visit with a provider.

Patients who are enrolled in IRB: IRB00075499 (PI: Dr. Chetan Bettagowda) may be eligible for this trial as well. Once identified as a potential study participant, the study team for this ctDNA study would have to confirm eligibility as for any potential participant.

In addition, potential participants may contact the study team directly.

Some of these potential participants may also be identified during the multidisciplinary clinic as part of the standard clinic case review process.

Description

Inclusion Criteria:

• Age ≥18 years
• Histologically proven chordoma of the skull base, spine, or sacrum (coccyx lesions are eligible).
• Radiographic evidence of spinal sacral chordoma is required and may be obtained from computed tomography imaging and/or magnetic resonance imaging. Other studies may be used with principal investigator approval.

Note: Patients enrolled in Dr. Chetan Bettegowda's J1576 study, (IRB00075499) may be considered eligible for this trial. The J1576 study enrolls patients who have been diagnosed with Chordoma. Prior to enrollment, all patients must be consented specifically for participation in this Chordoma study (IRB00291203).

• Treating physician must deem that neoadjuvant proton therapy or SBRT is appropriate treatment for the chordoma.
• Surgical resection with curative intent must be planned.
• The patient must have a Karnofsky Performance Score of 40 or greater.
• If a woman is of child-bearing potential, a negative urine or serum pregnancy test must be demonstrated prior to treatment. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation and for up to 12 weeks following the study. Should a woman become pregnant or suspect she is pregnant while participating in this study she should inform her treating physician immediately.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Prior radiation or radiosurgery to the involved level of the spine.
• Patients with metastatic disease will be excluded.
• Prior malignancies are excluded except for adequately treated basal cell or squamous cell skin cancer, cervical carcinoma in situ, or other cancer from which the patient has been disease free for at least 1 year.
• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements will be excluded.
• Pregnant women are excluded. Women of child-bearing potential who are unwilling or unable to use and acceptable method of birth control to avoid pregnancy for the entire study period and up to 12 weeks after the study are excluded. Male subjects must also agree to use effective contraception for the same period as above.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Spinal, Sacral Chordoma	Diagnostic test: ctDNA; the effects of neoadjuvant RT, in the form of either proton therapy or SBRT, on the ctDNA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity and specificity of combining ctDNA and radiomics	Sensitivity and specificity of combining ctDNA and radiomic features in predicting histopathologic changes at surgery defined by patients who have <10% necrosis, the percentage of patients who are deemed "positive" by the model based on ctDNA and radiomics	within one week after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of necrotic and active tumor cells	Percent of necrotic and active tumor cells following neoadjuvant RT using proton therapy or SBRT according to the Johns Hopkins Solid Tumor Panel Next Generation Sequencing	within one week after surgery
Change in plasma ctDNA levels	Change in plasma ctDNA levels following neoadjuvant RT for spinal chordoma and correlate changes in ctDNA levels with histopathologic changes at surgery	within one week after surgery
Correlate radiomic features with histopathologic and genomic features	Correlate radiomic features with histopathologic and genomic features in patients receiving neoadjuvant RT for spinal and sacral chordoma	within one week after surgery
Rate of wound healing complications	Rate of wound healing complications following neoadjuvant RT for spinal chordoma	within one week after surgery
Health related quality of life as assessed by the European Organization for Research and Treatment of Cancer (EORTC) quality of life (QLQ-C15-PAL) questionnaire	Health related quality of life following neoadjuvant RT for spinal chordoma measured by the European Organization for Research and Treatment of Cancer (EORTC) quality of life (QLQ-C15-PAL) questionnaire. The scoring ranges from 0-21, with 21 being the highest quality of life.	within one week after surgery
Local progression free survival	Local progression free survival following neoadjuvant RT for spinal chordoma	3 years
Overall survival	Overall survival following neoadjuvant RT for spinal chordoma	3 years
Relationship between ctDNA post-op and local Progression Free Survival (PFS)	The relationship between circulating tumor DNA post-operatively and local PFS following neoadjuvant RT for spinal chordoma	3 years
Relationship between ctDNA post-op and Overall Survival (OS)	The relationship between circulating tumor DNA post-operatively and OS following neoadjuvant RT for spinal chordoma	3 years
Toxicity of neoadjuvant RT as assessed by CTCAE version 5	Toxicity of neoadjuvant RT for chordoma using CTCAE version 5	3 years
Radiographic local recurrence	Radiographic local recurrence defined as evidence of progressive disease on CT/MRI in the operative site when compared to post-op imaging.	within one week after surgery

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Canon Medical Systems, USA
• Investigators: Principal Investigator: Kristin Redmond, MD, MPH, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2024
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2031

Study Registration Dates

• First Submitted: June 12, 2024
• First Submitted That Met QC Criteria: June 12, 2024
• First Posted (Actual): June 17, 2024

Study Record Updates

• Last Update Posted (Estimated): October 24, 2025
• Last Update Submitted That Met QC Criteria: October 22, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Germ Cell and Embryonal; Chordoma
• Other Study ID Numbers: J2317; IRB00291203 (Other Identifier: JHM IRB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No