Clinical trial NCT06463262: Exploration of Personalized Biomarkers During Neoadjuvant Radiation Therapy for Spinal and Sacral Chordoma
Official title: Exploration of Personalized Biomarkers During Neoadjuvant Radiation Therapy for Spinal and Sacral Chordoma
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Chordoma of Spine
Chordoma of Skull Base
Chordoma of Sacrum
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: Canon Medical Systems, USA
First posted: 2024-06-17
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Sensitivity and specificity of combining ctDNA and radiomics
timeFrame: within one week after surgery
Secondary outcomes:
measure: Percent of necrotic and active tumor cells
timeFrame: within one week after surgery
measure: Change in plasma ctDNA levels
timeFrame: within one week after surgery
measure: Correlate radiomic features with histopathologic and genomic features
timeFrame: within one week after surgery
measure: Radiographic local recurrence
timeFrame: within one week after surgery
measure: Rate of wound healing complications
timeFrame: within one week after surgery
measure: 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
timeFrame: within one week after surgery
measure: Local progression free survival
timeFrame: 3 years
measure: Overall survival
timeFrame: 3 years
measure: Relationship between ctDNA post-op and local Progression Free Survival (PFS)
timeFrame: 3 years
measure: Relationship between ctDNA post-op and Overall Survival (OS)
timeFrame: 3 years
measure: Toxicity of neoadjuvant RT as assessed by CTCAE version 5
timeFrame: 3 years
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Kristin Redmond, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: