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

Chordoma of Sacrum Clinical Trial

— Canon  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06463262
• Other study ID #: J2317
• Secondary ID: IRB00291203
• Status: Not yet recruiting
• Start date: July 2024
• Est. completion date: July 2031

Study information

• Verified date: June 2024
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: Kristin Redmond, MD, MPH
• Phone: 4106141642
• Email: kjanson3[@]jhmi.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: July 2031
• Est. primary completion date: July 2029
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chordoma
• Chordoma of Sacrum
• Chordoma of Spine

Intervention

Diagnostic Test:
• ctDNA
the effects of neoadjuvant RT, in the form of either proton therapy or SBRT, on the ctDNA

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Canon Medical Systems, USA

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Rate of wound healing complications	Rate of wound healing complications following neoadjuvant RT for spinal chordoma	within one week after surgery
Secondary	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
Secondary	Local progression free survival	Local progression free survival following neoadjuvant RT for spinal chordoma	3 years
Secondary	Overall survival	Overall survival following neoadjuvant RT for spinal chordoma	3 years
Secondary	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
Secondary	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
Secondary	Toxicity of neoadjuvant RT as assessed by CTCAE version 5	Toxicity of neoadjuvant RT for chordoma using CTCAE version 5	3 years