Precision Radiotherapy Enabled by Molecular MRI

This is a research study to determine if a novel molecular magnetic resonance imaging (MRI) technique, called amide proton transfer (APT) imaging, is useful in identifying the most aggressive areas of tumor needed for radiotherapy of brain tumors.

Study Overview

• Status: Recruiting
• Conditions: Brain Cancer
• Intervention / Treatment: Radiation: Amide proton transfer radiotherapy; Radiation: Standard radiotherapy

Detailed Description

Despite advances in therapy, glioblastoma remains almost universally fatal, with a high rate of local failure and a median survival of < 2 years. The standard of care for GBM is maximum safe surgical resection, followed by radiotherapy (RT) with temozolomide (TMZ) chemotherapy, which was established two decades ago. There is an urgent need to optimize each step of this standard therapy and develop new methods to fight this devastating disease. It is the infiltrative nature of GBM that limits resection and leads to suboptimal RT planning. To address this, neurosurgeons are employing supratotal resection, in which gadolinium-enhancing macroscopic tumor plus 1-2 cm extension into gadolinium-non-enhancing peritumoral regions is resected after preserving the highly eloquent region.

RT planning is complex and varies among medical centers, particularly in terms of inclusion of non-enhancing peritumoral regions in the clinical target volume. Moreover, lack of local therapy intensification of RT is considered one of the factors that prevent this standard therapy from achieving maximal tumor control. New RT approaches, such as focused dose escalation and proton therapy, require the best possible imaging methods to accurately visualize the extent of the tumor. Furthermore, standard structural MRI cannot distinguish between treatment effect from RT and tumor progression. Notably, the treated tumor may have progressed during fractionated RT, and the newly emerging active lesion could be missed from the original RT planning, particularly at the boost phase. New tissue-specific imaging approaches, like amide proton transfer (APT) imaging, that can accurately identify the tumor burden before, during, and after RT treatment are urgently needed.

The investigators central hypothesis in this highly innovative and clinically significant study is that protein-based APT-MRI is capable of identifying a precise high-protein tumor hotspot inside and outside Gd-enhancing regions with which to guide radiation dose escalation to high-risk active tumor and to facilitate an adaptive strategy to regions of therapeutic resistance during RT.

The innovative APT-RT technique developed by the investigators at Johns Hopkins enables a personalized RT regimen with precise dose escalation in high-risk tumor regions and response-adapted dose escalation in therapeutically resistant lesions in the boost phase, which could decrease the local recurrence rate. Personalized local therapy intensification would achieve maximal tumor control and improve the survival for GBM patients. The investigator's preliminary study will lay the foundation for a more definitive phase-II prospective clinical trial to assess the impact of APT imaging on RT guidance with regard to outcomes, including overall and progression-free survival, complications, toxicity, and quality of life. The investigators expect that APT-RT should be more effective for tumor control than the current conventional therapy.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ryan Manuel; Phone Number: 410-955-4261; Email: rmanuel5@jhmi.edu
• Study Contact Backup: Name: Kristin Redmond; Phone Number: 410-614-1642; Email: kjanson3@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins University
      • Contact: Dana B Kaplin, MPH; Phone Number: 410-614-3950; Email: dkaplin1@jhmi.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologic confirmation of glioblastoma or grade 4 astrocytoma
• Age >18
• KPS at least 60

• Patients must have normal organ and marrow function as defined below:

  • leukocytes >3,000/mcL
  • absolute neutrophil count >1,500/mcL
  • platelets >100,000/mcL
  • total bilirubin within normal institutional limits
  • AST(SGOT)/ALT(SGPT) <2.5
  • institutional upper limit of normal
  • creatinine within normal institutional limits OR creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
• Patients of child-bearing potential (male or female) must practice adequate contraception due to possible harmful effects of radiation therapy on an unborn child.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Patients who are unable to receive MRIs will be excluded from the study.
• Patients may not be receiving any other investigational cancer treatment agents at the time of enrollment.
• Patients may not have previously been treated with an overlapping course of radiotherapy to the brain.
• 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.
• Pregnant and/or breastfeeding women are excluded. Women of child-bearing potential who are unwilling or unable to use an 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?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Amide proton transfer radiotherapy (APT-RT); Amide proton transfer radiotherapy (APT-RT) is weighted imaging that may enhance visualization of tumor infiltration and could reduce the risk of radiation toxicity while still effectively irradiating the tumor.	Radiation: Amide proton transfer radiotherapy; New APT-RT regimen; Other Names: APT-RT
Active Comparator: Standard radiotherapy (RT)	Radiation: Standard radiotherapy; Standard two-phase RT; Other Names: RT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in APTw signal (Efficacy of APT-RT)	A reduction in APTw signal following treatment suggests a positive response to therapy (active tumor APTw = 3-4% vs. necrosis/no tumor APTw 1-2%). A 1% greater reduction in mean APTw signal change within the Gd-enhancing tumor region from baseline (pre-RT) to post-RT in the APT-RT arm, compared to the control arm.	From baseline to 4 weeks post completion of RT.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival will be measured for each patient from randomization to the date of death.	Randomization up to 2 years post completion of RT.
Progression free survival	Progression free survival will be measured for each patient from randomization to the date of progressive disease or death, whichever occurs first. The definition of progression will be based on RANO criteria.	From randomization up to 2 years post completion of RT.
Toxicity and radiation as assessed by grade 3 or greater neurologic toxicity	All patients who receive any amount of RT will be evaluable for toxicity. CTCAE version 5 will be used to record grade 3 or greater neurologic toxicity.	Baseline, Treatment weeks 1 - 6, Follow-ups: 6 month, 12 month, 24 month
Radiation as assessed by grade 3 or greater neurologic toxicity	All patients who receive any amount of RT will be evaluable for toxicity. RTOG/EORTC acute and late radiation morbidity score will be used to record grade 3 or greater neurologic toxicity.	Baseline, Treatment weeks 1 - 6, Follow-ups: 6 month, 12 month, 24 month
Quality of Life as assessed by EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20)	EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) will be recorded for each patient. Score range 0-100. higher score, better quality of life. In case of disease progression within 2 years of cycle 1, patients will be re-tested for the final time only if previous assessment was >3 months from date of progression.	Baseline (≤21 days before starting RT), 1 month follow-up (≤10 days prior to cycle 1 of adjuvant TMZ), and every 6 months (+/- 1 month) up to 2 years from completion of RT.
Quality of Life as assessed by the M. D. Anderson Symptom Inventory Brain Tumor Module (MDASI-BT)	M. D. Anderson Symptom Inventory Brain Tumor Module (MDASI-BT) will be recorded for each patient. Score ranges from 0 (best condition) to 10 (worst condition) In case of disease progression within 2 years of cycle 1, patients will be re-tested for the final time only if previous assessment was >3 months from date of progression.	Baseline (≤21 days before starting RT), 1 month follow-up (≤10 days prior to cycle 1 of adjuvant TMZ), and every 6 months (+/- 1 month) up to 2 years from completion of RT.

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: The Ben & Catherine Ivy Foundation
• Investigators: Principal Investigator: Kristin Redmond, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2026
• Primary Completion (Estimated): May 1, 2031
• Study Completion (Estimated): May 1, 2032

Study Registration Dates

• First Submitted: March 30, 2026
• First Submitted That Met QC Criteria: March 30, 2026
• First Posted (Actual): April 6, 2026

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Glioblastoma
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Central Nervous System Neoplasms; Glioblastoma; Brain Neoplasms
• Other Study ID Numbers: J2568; IRB00505816 (Other Identifier: Johns Hopkins 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