68Ga-Dotatate PET and MRI Guided Radiation Dose Escalation for High Risk Meningioma

Phase 1 Trial of 68Ga-Dotatate PET and MRI Guided Radiation Dose Escalation for High-Risk Meningiomas

The is phase 1 trial of 68Ga-Dotatate PET/MRI guided radiation dose escalation for high-risk meningiomas (defined as recurrent or subtotal resection of Grade 2, and any Grade 3 meningioma). A modified toxicity probability interval schedule will be implemented with a Bayesian Optimal interval suite. It includes 4 dose cohort (66 Gy, 69 Gy, 72 Gy and 75 Gy). The initial study cohort will include 3 patients treated with 69 Gy in 30 daily fractions. The investigators will seek to determine the MTD of radiation therapy based DLTs.

Study Overview

• Status: Suspended
• Conditions: Recurrent Meningioma; High Risk Meningioma
• Intervention / Treatment: Radiation: ⁶⁸Ga-Dotatate PET and MRI Guided Radiation Therapy; Diagnostic test: Magnetic Resonance Imaging (MRI); Diagnostic test: 68Ga-Dotatate PET Imaging; Other: MD Anderson Symptom Inventory Bain Tumor form (MDASI-BT); Diagnostic test: EuroQol-5 Dimension (ED-5D)

Detailed Description

Patient will be enrolled, and dose selected per modified toxicity probability interval utilizing a Bayesian Optimal interval suite to maximize the probability that selecting the MTD dose that has a target DLT rate under 30% while optimizing patient safety over the 3+3 trial design 15. For our initial cohort the investigators will seek to treat 3 patients at 69 Gy in 30 daily fractions, Monday-Friday for 6 weeks of treatment utilizing MRI/PET target delineation with IMRT/VMAT. Patients will be followed weekly for on-treatment visits and 30 days from end of radiation to evaluate for DLTs classified as grade 3+ toxicity by NCI-CTCAE v5.0. Subsequent dosing will be determined by DLTs experienced utilizing a modified toxicity probability interval design. If the stopping rule is met, the trial will discontinue enrollment and select the MTD. If the stopping rule is not met, the DLT rate will be computed at the current treated dose. DLT rate is calculated by the total number of patients experiencing DLT at the current dose divided by total number of evaluable patients at the current dose. With a DLT rate of less than or equal to 0.236 dose will be escalated by 3 Gy, DLT rate greater than 0.359 will de-escalate the dose by 3 Gy. A rate between 0.236 and 0.359 will retain the current dose. An additional 3 patients will then be enrolled at specified dose depending on DLT rate. Patients will be treated and followed to assess for acute DLTs. The process will be repeated with enrollment discontinued if stopping rule met or additional patient will be enrolled at a dose from 66 - 75 Gy in 30 fractions based on new DLT rate. Enrollment utilizing DLT rate will be discontinued once stopping rule met or 12 patients are enrolled and an MTD will be established. Once the MTD has been established, an additional 12 patients at the MTD will then be enrolled.

Following radiation treatment (with once weekly on-treatment visits) and evaluation 1 month following completion for radiation, patients will be evaluated 3-, 6-, 9, 12-, 18-, and 24-months post-treatment utilizing NCI-CTCAEv5.0, symptom burden and QOL questionnaires, and MRI imaging to evaluate for safety, toxicity, and treatment efficacy.

The study population will include any adult patients, with high-risk meningioma as defined by RTOG definition (Grade 2 meningioma with subtotal resection or recurrence, and any Grade 3 meningioma).

It is believed dose escalation with IMRT/VMAT therapy is feasible and well tolerated with improved target delineation utilizing both MRI and PET fusion with an acceptable toxicity profile.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Sidney Kimmel Cancer Center at Thomas Jefferson University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Individuals must meet all the following inclusion criteria in order to be eligible to participate in the study:

  1. Adult patients, age ≥ 18 years

  2. Patients with RTOG Group III meningioma (high risk) defined as:

     • Patients with newly diagnosed or a recurrent WHO grade 3 meningioma of any resection extent.
     • or patients with a recurrent WHO grade 2 meningioma of any resection extent.
     • or patient with a newly diagnosed sub-totally resected (residual nodular enhancement or PET enhancement on postoperative imaging, or Simpson grade IV or V excision) WHO grade 2 meningioma.
  3. In the setting of newly diagnosed meningioma, the histologic diagnosis must be within 6 months of registration.
  4. In the setting of a recurrent meningioma, there are no such time constraints. However, additional resection or biopsy is encouraged for patients with recurrence but is not requisite. If further biopsy or resection is performed at recurrence, it must be within 6 months of registration.
  5. Karnofsky Performance Status 60-100
  6. MRI brain and ⁶⁸Ga-Dotatate PET must be performed within 6 weeks prior to registration.

  7. For woman of childbearing potential:

     • A negative serum pregnancy test is required within 14 days prior to registration.
     • The patient must agree to practice adequate contraception from the time of the negative serum pregnancy test throughout the entire course of EBRT.

Exclusion Criteria:

• An individual who meets any of the following criteria will be excluded from participation in this study:

  1. Extracranial meningioma
  2. Prior radiation therapy to the scalp, cranium, brain, or skull base
  3. Prior malignancy (except for non-melanomatous skin cancer), unless disease free for at least 3 years
  4. Pregnancy or lactation
  5. Treatment with another investigational drug or other intervention at time of registration
  6. Inability to receive gadolinium or undergo MRI brain or ⁶⁸Ga-Dotatate PET imaging.
  7. Serious medical or psychiatric illness likely to interfere with participation in this clinical trial.
  8. Evidence of increased intracranial pressure (midline shift > 5mm, clinically significant papilledema)
  9. Uncontrolled seizure

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: Dose Level 1 - 66 Gy; Participants receive 68Ga-Dotatate PET and MRI guided external beam radiation therapy (EBRT) with intensity-modular radiation therapy (IMRT) or volumetric arc radiation therapy (VMAT). Two planning target volumes (PTV) will be required, including PTV and PTV-high. PTV_High will be given a dose of 66 Gy in 30 once daily fractions. PTV will receive 60 Gy in 30 fractions concurrently.	Radiation: ⁶⁸Ga-Dotatate PET and MRI Guided Radiation Therapy; The radiation dose levels will be 66, 69, 72, and 75 Gy in 30 daily fractions based on the design.; Diagnostic test: Magnetic Resonance Imaging (MRI); MRI brain with and without contrast must be performed within 6 weeks prior to registration. MRI brain will be performed at 3-, 6-, 9-, 12-, 18-, and 24 months. If surgery is performed, MRI must be performed after surgery.; Other Names: MRI; Diagnostic test: 68Ga-Dotatate PET Imaging; ⁶⁸(GA)Dotatate PET must be performed within 6 weeks prior to registration. 12 months after radiation treatment +/- 1 month patients are required to get Ga-Dotatate PET.; Other Names: GaTate PET; Gallium-68 DOTATATE Scan; DOTA-TATE imaging; Other: MD Anderson Symptom Inventory Bain Tumor form (MDASI-BT); Every 3 m ± 2 weeks, starting 3 m ± 2 weeks post radiation treatment. MRI at the 9 month post radiation visit is only to be completed if per physician discretion it is clinically indicated, except for patients with grade 3 meningioma, the 9 month MRI is required. At month 18 ± 4 weeks, and month 24 ± 4 weeks after radiation treatment.; Other Names: Survey; Diagnostic test: EuroQol-5 Dimension (ED-5D); Every 3 m ± 2 weeks, starting 3 m ± 2 weeks post radiation treatment. MRI at the 9 month post radiation visit is only to be completed if per physician discretion it is clinically indicated, except for patients with grade 3 meningioma, the 9 month MRI is required. At month 18 ± 4 weeks, and month 24 ± 4 weeks after radiation treatment.; Other Names: Survey
Experimental: Arm 2: Dose Level 2 - 69 Gy; Participants receive 68Ga-Dotatate PET and MRI guided external beam radiation therapy (EBRT) with intensity-modular radiation therapy (IMRT) or volumetric arc radiation therapy (VMAT). Two planning target volumes (PTV) will be required, including PTV and PTV-high. PTV_High will be given a dose of 69 Gy in 30 once daily fractions. PTV will receive 60 Gy in 30 fractions concurrently.	Radiation: ⁶⁸Ga-Dotatate PET and MRI Guided Radiation Therapy; The radiation dose levels will be 66, 69, 72, and 75 Gy in 30 daily fractions based on the design.; Diagnostic test: Magnetic Resonance Imaging (MRI); MRI brain with and without contrast must be performed within 6 weeks prior to registration. MRI brain will be performed at 3-, 6-, 9-, 12-, 18-, and 24 months. If surgery is performed, MRI must be performed after surgery.; Other Names: MRI; Diagnostic test: 68Ga-Dotatate PET Imaging; ⁶⁸(GA)Dotatate PET must be performed within 6 weeks prior to registration. 12 months after radiation treatment +/- 1 month patients are required to get Ga-Dotatate PET.; Other Names: GaTate PET; Gallium-68 DOTATATE Scan; DOTA-TATE imaging; Other: MD Anderson Symptom Inventory Bain Tumor form (MDASI-BT); Every 3 m ± 2 weeks, starting 3 m ± 2 weeks post radiation treatment. MRI at the 9 month post radiation visit is only to be completed if per physician discretion it is clinically indicated, except for patients with grade 3 meningioma, the 9 month MRI is required. At month 18 ± 4 weeks, and month 24 ± 4 weeks after radiation treatment.; Other Names: Survey; Diagnostic test: EuroQol-5 Dimension (ED-5D); Every 3 m ± 2 weeks, starting 3 m ± 2 weeks post radiation treatment. MRI at the 9 month post radiation visit is only to be completed if per physician discretion it is clinically indicated, except for patients with grade 3 meningioma, the 9 month MRI is required. At month 18 ± 4 weeks, and month 24 ± 4 weeks after radiation treatment.; Other Names: Survey
Experimental: Arm 3: Dose Level 3 - 72 Gy; Participants receive 68Ga-Dotatate PET and MRI guided external beam radiation therapy (EBRT) with intensity-modular radiation therapy (IMRT) or volumetric arc radiation therapy (VMAT). Two planning target volumes (PTV) will be required, including PTV and PTV-high. PTV_High will be given a dose of 72 Gy in 30 once daily fractions. PTV will receive 60 Gy in 30 fractions concurrently.	Radiation: ⁶⁸Ga-Dotatate PET and MRI Guided Radiation Therapy; The radiation dose levels will be 66, 69, 72, and 75 Gy in 30 daily fractions based on the design.; Diagnostic test: Magnetic Resonance Imaging (MRI); MRI brain with and without contrast must be performed within 6 weeks prior to registration. MRI brain will be performed at 3-, 6-, 9-, 12-, 18-, and 24 months. If surgery is performed, MRI must be performed after surgery.; Other Names: MRI; Diagnostic test: 68Ga-Dotatate PET Imaging; ⁶⁸(GA)Dotatate PET must be performed within 6 weeks prior to registration. 12 months after radiation treatment +/- 1 month patients are required to get Ga-Dotatate PET.; Other Names: GaTate PET; Gallium-68 DOTATATE Scan; DOTA-TATE imaging; Other: MD Anderson Symptom Inventory Bain Tumor form (MDASI-BT); Every 3 m ± 2 weeks, starting 3 m ± 2 weeks post radiation treatment. MRI at the 9 month post radiation visit is only to be completed if per physician discretion it is clinically indicated, except for patients with grade 3 meningioma, the 9 month MRI is required. At month 18 ± 4 weeks, and month 24 ± 4 weeks after radiation treatment.; Other Names: Survey; Diagnostic test: EuroQol-5 Dimension (ED-5D); Every 3 m ± 2 weeks, starting 3 m ± 2 weeks post radiation treatment. MRI at the 9 month post radiation visit is only to be completed if per physician discretion it is clinically indicated, except for patients with grade 3 meningioma, the 9 month MRI is required. At month 18 ± 4 weeks, and month 24 ± 4 weeks after radiation treatment.; Other Names: Survey
Experimental: Arm 4: Dose Level 4 - 75 Gy; Participants receive 68Ga-Dotatate PET and MRI guided external beam radiation therapy (EBRT) with intensity-modular radiation therapy (IMRT) or volumetric arc radiation therapy (VMAT). Two planning target volumes (PTV) will be required, including PTV and PTV-high. PTV_High will be given a dose of 75 Gy in 30 once daily fractions. PTV will receive 60 Gy in 30 fractions concurrently.	Radiation: ⁶⁸Ga-Dotatate PET and MRI Guided Radiation Therapy; The radiation dose levels will be 66, 69, 72, and 75 Gy in 30 daily fractions based on the design.; Diagnostic test: Magnetic Resonance Imaging (MRI); MRI brain with and without contrast must be performed within 6 weeks prior to registration. MRI brain will be performed at 3-, 6-, 9-, 12-, 18-, and 24 months. If surgery is performed, MRI must be performed after surgery.; Other Names: MRI; Diagnostic test: 68Ga-Dotatate PET Imaging; ⁶⁸(GA)Dotatate PET must be performed within 6 weeks prior to registration. 12 months after radiation treatment +/- 1 month patients are required to get Ga-Dotatate PET.; Other Names: GaTate PET; Gallium-68 DOTATATE Scan; DOTA-TATE imaging; Other: MD Anderson Symptom Inventory Bain Tumor form (MDASI-BT); Every 3 m ± 2 weeks, starting 3 m ± 2 weeks post radiation treatment. MRI at the 9 month post radiation visit is only to be completed if per physician discretion it is clinically indicated, except for patients with grade 3 meningioma, the 9 month MRI is required. At month 18 ± 4 weeks, and month 24 ± 4 weeks after radiation treatment.; Other Names: Survey; Diagnostic test: EuroQol-5 Dimension (ED-5D); Every 3 m ± 2 weeks, starting 3 m ± 2 weeks post radiation treatment. MRI at the 9 month post radiation visit is only to be completed if per physician discretion it is clinically indicated, except for patients with grade 3 meningioma, the 9 month MRI is required. At month 18 ± 4 weeks, and month 24 ± 4 weeks after radiation treatment.; Other Names: Survey
Experimental: MTD Expansion Cohort; Once the maximum tolerated dose (MTD) is established, an additional 12 patients will be enrolled at that dose level. Participants will receive 68Ga-Dotatate PET imaging and MRI-guided external beam radiation therapy (EBRT), delivered using either intensity-modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT). Two planning target volumes (PTVs) will be defined: PTV and PTV-High. PTV-High will receive the MTD (in Gy) delivered in 30 once-daily fractions. PTV will concurrently receive 60 Gy in 30 fractions.	Radiation: ⁶⁸Ga-Dotatate PET and MRI Guided Radiation Therapy; The radiation dose levels will be 66, 69, 72, and 75 Gy in 30 daily fractions based on the design.; Diagnostic test: Magnetic Resonance Imaging (MRI); MRI brain with and without contrast must be performed within 6 weeks prior to registration. MRI brain will be performed at 3-, 6-, 9-, 12-, 18-, and 24 months. If surgery is performed, MRI must be performed after surgery.; Other Names: MRI; Diagnostic test: 68Ga-Dotatate PET Imaging; ⁶⁸(GA)Dotatate PET must be performed within 6 weeks prior to registration. 12 months after radiation treatment +/- 1 month patients are required to get Ga-Dotatate PET.; Other Names: GaTate PET; Gallium-68 DOTATATE Scan; DOTA-TATE imaging; Other: MD Anderson Symptom Inventory Bain Tumor form (MDASI-BT); Every 3 m ± 2 weeks, starting 3 m ± 2 weeks post radiation treatment. MRI at the 9 month post radiation visit is only to be completed if per physician discretion it is clinically indicated, except for patients with grade 3 meningioma, the 9 month MRI is required. At month 18 ± 4 weeks, and month 24 ± 4 weeks after radiation treatment.; Other Names: Survey; Diagnostic test: EuroQol-5 Dimension (ED-5D); Every 3 m ± 2 weeks, starting 3 m ± 2 weeks post radiation treatment. MRI at the 9 month post radiation visit is only to be completed if per physician discretion it is clinically indicated, except for patients with grade 3 meningioma, the 9 month MRI is required. At month 18 ± 4 weeks, and month 24 ± 4 weeks after radiation treatment.; Other Names: Survey

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose of 68Ga-Dotatate PET/MRI guided radiation dose escalation	To establish MTD utilizing DLT rates (DLT will be defined as radiation treatment related G3 or higher neurological toxicity from beginning of radiation till 30 days after finishing radiation treatment).	30 days post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Late Neurological Toxicities of Radiation Treatment	Number of participants experiencing radiation treatment related G3 or higher neurological toxicity from beginning of radiation till 30 days after finishing radiation treatment.	up to 2 year post-treatment
Symptom Burden Assessment Using MD Anderson Symptom Inventory - Brain Tumor (MDASI - BT) Questionnaire	Patient reported symptom severity and interference will be assessed using the MD Anderson Symptom Inventory - Brain Tumor (MDASI - BT) Questionnaire. It consists of 23 symptoms rated on an 11-point scale (0 to 10) to indicate the presence and severity of the symptom, with 0 being "not present" and 10 being "as bad as you can imagine." Each symptom is rated at its worst in the last 24 hours. The interference items also are measured on 0-10 scales.	Baseline
Symptom Burden Assessment Using MD Anderson Symptom Inventory - Brain Tumor (MDASI - BT) Questionnaire	Patient reported symptom severity and interference will be assessed using the MD Anderson Symptom Inventory - Brain Tumor (MDASI - BT) Questionnaire. It consists of 23 symptoms rated on an 11-point scale (0 to 10) to indicate the presence and severity of the symptom, with 0 being "not present" and 10 being "as bad as you can imagine." Each symptom is rated at its worst in the last 24 hours. The interference items also are measured on 0-10 scales.	3 months (+/- 2 weeks)
Symptom Burden Assessment Using MD Anderson Symptom Inventory - Brain Tumor (MDASI - BT) Questionnaire	Patient reported symptom severity and interference will be assessed using the MD Anderson Symptom Inventory - Brain Tumor (MDASI - BT) Questionnaire. It consists of 23 symptoms rated on an 11-point scale (0 to 10) to indicate the presence and severity of the symptom, with 0 being "not present" and 10 being "as bad as you can imagine." Each symptom is rated at its worst in the last 24 hours. The interference items also are measured on 0-10 scales.	6 months (+/- 2 weeks)
Symptom Burden Assessment Using MD Anderson Symptom Inventory - Brain Tumor (MDASI - BT) Questionnaire	Patient reported symptom severity and interference will be assessed using the MD Anderson Symptom Inventory - Brain Tumor (MDASI - BT) Questionnaire. It consists of 23 symptoms rated on an 11-point scale (0 to 10) to indicate the presence and severity of the symptom, with 0 being "not present" and 10 being "as bad as you can imagine." Each symptom is rated at its worst in the last 24 hours. The interference items also are measured on 0-10 scales.	9 months (+/- 2 weeks)
Symptom Burden Assessment Using MD Anderson Symptom Inventory - Brain Tumor (MDASI - BT) Questionnaire	Patient reported symptom severity and interference will be assessed using the MD Anderson Symptom Inventory - Brain Tumor (MDASI - BT) Questionnaire. It consists of 23 symptoms rated on an 11-point scale (0 to 10) to indicate the presence and severity of the symptom, with 0 being "not present" and 10 being "as bad as you can imagine." Each symptom is rated at its worst in the last 24 hours. The interference items also are measured on 0-10 scales.	12 months (+/- 2 weeks)
Symptom Burden Assessment Using MD Anderson Symptom Inventory - Brain Tumor (MDASI - BT) Questionnaire	Patient reported symptom severity and interference will be assessed using the MD Anderson Symptom Inventory - Brain Tumor (MDASI - BT) Questionnaire. It consists of 23 symptoms rated on an 11-point scale (0 to 10) to indicate the presence and severity of the symptom, with 0 being "not present" and 10 being "as bad as you can imagine." Each symptom is rated at its worst in the last 24 hours. The interference items also are measured on 0-10 scales.	18 months (+/- 4 weeks)
Symptom Burden Assessment Using MD Anderson Symptom Inventory - Brain Tumor (MDASI - BT) Questionnaire	Patient reported symptom severity and interference will be assessed using the MD Anderson Symptom Inventory - Brain Tumor (MDASI - BT) Questionnaire. It consists of 23 symptoms rated on an 11-point scale (0 to 10) to indicate the presence and severity of the symptom, with 0 being "not present" and 10 being "as bad as you can imagine." Each symptom is rated at its worst in the last 24 hours. The interference items also are measured on 0-10 scales.	24 months (+/- 4 weeks)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local Control at 1 year from Registration	Proportion of participants without local tumor progression.	at 1 year from Registration
Local Control at 2 years from Registration	Proportion of participants without local tumor progression.	at 2 years from Registration
Local Control at 3 years from Registration	Proportion of participants without local tumor progression.	at 3 years from Registration
Progression Free Survival at 1 year from Registration	Time from enrollment to disease progression or death from any cause, whichever occurs first.	at 1 year from Registration
Progression Free Survival at 2 years from Registration	Time from enrollment to disease progression or death from any cause, whichever occurs first.	at 2 years from Registration
Progression Free Survival at 3 years from Registration	Time from enrollment to disease progression or death from any cause, whichever occurs first.	at 3 years from Registration
Overall Survival at 1 year from Registration	Time from enrollment to death from any cause.	at 1 year from Registration
Overall Survival at 2 years from Registration	Time from enrollment to death from any cause.	at 2 years from Registration
Overall Survival at 3 years from Registration	Time from enrollment to death from any cause.	at 3 years from Registration

Collaborators and Investigators

• Sponsor: Thomas Jefferson University
• Investigators: Principal Investigator: Wenyin Shi, MD, PhD, Wenyin.Shi@jefferson.edu

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: January 13, 2026
• First Submitted That Met QC Criteria: January 13, 2026
• First Posted (Actual): January 20, 2026

Study Record Updates

• Last Update Posted (Actual): January 23, 2026
• Last Update Submitted That Met QC Criteria: January 21, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: maximum tolerated dose; High-Risk Meningiomas; subtotal resection of Grade 2 meningioma; subtotal resection of Grade 3 meningioma; recurrent meningioma; 68Ga-Dotatate PET; MRI Guided Radiation; BOIN
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Central Nervous System Neoplasms; Meningioma; Health Care Quality, Access, and Evaluation; Investigative Techniques; Epidemiologic Methods; Diagnostic Techniques and Procedures; Diagnosis; Data Collection; Health Care Evaluation Mechanisms; Quality of Health Care; Public Health; Environment and Public Health; Tomography; Diagnostic Imaging; Reproductive Physiological Phenomena; Reproductive and Urinary Physiological Phenomena; Surveys and Questionnaires; Magnetic Resonance Imaging; Fertility
• Other Study ID Numbers: iRIS ID-2023-2983; JT 38404 (Other Identifier: JeffTrial Number)

Drug and device information, study documents

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