68Ga/177Lu-PSMA Theranostics in Recurrent Grade 3 and Grade 4 Glioma

This interventional, clinical pilot-study will initiate and evaluate 68Ga/177Lu-PSMA theranostics in Norway as treatment alternative for patients with recurrent grade 3 and grade 4 gliomas. The main goal is to improve existing diagnostic and therapeutic methods in glioma management, and introduce a novel, well-tolerated radionuclide treatment that possibly can increase the overall survival and quality of life for a patient group that today have very short expected survival and no standard recommended therapy.

Study Overview

• Status: Recruiting
• Conditions: High Grade Glioma
• Intervention / Treatment: Radiation: 177Lu-PSMA I&T

Detailed Description

Patients demonstrating a high tumor uptake of 68Ga-PSMA on the diagnostic PET/MRI examination in the screening part of the study are eligible for a standard of 3 cycles, with a possible extension to maximum number of 6 cycles, of 177Lu-PSMA radionuclide therapy sessions. SPECT/CT will be performed after each cycle of treatment for dosimetry calculations, while 68Ga-PSMA PET/MRI, quality-of-life schemes and clinical examinations will be used to monitor therapeutic effects during the therapy cycles and up to 1.5 year after treatment initiation. The main endpoints of the study are progression-free survival and overall survival.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tora Solheim, MD/PhD; Phone Number: +4772826136; Email: tora.solheim@ntnu.no
• Study Contact Backup: Name: Live Eikenes, PhD; Phone Number: +4799568081; Email: live.eikenes@ntnu.no

Study Locations

• Norway
  • Trondheim, Norway
    • Recruiting
    • St. Olavs Hospital
    • Contact: Live Eikenes, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• A previous diagnosis of histologically confirmed WHO grade 3 or grade 4 glioma
• Radiologically (MRI) confirmed tumor relapse/progression ≥ 12 weeks since completed radiotherapy or suspicion of recurrence where inclusion in the theranostic part of study could be indicated
• Must be ≥ 18 years old
• Written informed consent for study participation
• Negative pregnancy test no longer than 14 days prior to enrollment
• Life expectancy > 12 weeks
• Karnofsky performance status ≥ 70% (must be able to care for self after radionuclide therapy)
• High tumor uptake on diagnostic imaging with 68Ga -PSMA.
• Tumor not amendable for radiotherapy or surgery, and treating oncologist think that there are no other preferable systemic therapy options (e.g temozolomide, PCV or lomustine monotherapy).

• Women of childbearing potential (WOCBP) defined as fertile, following menarche and until becoming post-menopausal unless permanently sterile must use adequate contraception. Permanent sterilization methods include hysterectomy, bilateral salpingectomy or bilateral oophorectomy. Adequate contraception in the current study will be the following:

  o Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:

  • Intravaginal
  • transdermal
  • Progestogen-only hormonal contraception associated with inhibition of ovulation:
  • oral
  • injectable
  • implantable
  • intrauterine device (IUD)
  • intrauterine hormone-releasing system ( IUS)
  • bilateral tubal occlusion
  • vasectomised partner
  • sexual abstinence
• Patient accept not to receive any other tumor directed treatment before 8 weeks after each 177Lu-PSMA injection.

Exclusion Criteria:

• Estimated GFR < 30 mL/min
• Platelet count <75 x109 /L
• White blood cells ≤ 2.5 x 109/L
• Neutrophil count < 1.5 x109 /L
• Hb < 8.0 g/dL
• Albumin ≤ 25 g/L
• Uncontrollable symptomatic epilepsy refractory to standard medication
• Pacemakers or defibrillators not compatible with 3T MRI
• No ability to obtain informed consent (e.g. due to severe dysphasia or cognitive deficits).
• Breastfeeding
• Pregnancy
• Hypersensitivity to the active substance or to any of the excipients
• Urinary and fecal incontinence (patient cannot have diaper needs)
• Significant medical or psychiatric illness that, in the investigator's opinion, would compromise the patient's ability to tolerate this therapy
• If previous radiotherapy and/or radionuclide therapy have resulted in absorbed doses >=23 Gy to any of the kidneys, or >= 25 Gy to any of the parotids, an individual assessment will be made by the nuclear medicine physician and medical physicist if patient can be included to the therapy part of the study.
• Concurrent investigational drugs or experimental therapy must be stopped at least 4 weeks prior to study entry
• Unwilling to accept potential challenge with xerostomia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 68Ga/177Lu-PSMA theranostics in recurrent grade 3 and grade 4 glioma; Patients demonstrating a high tumor uptake of 68Ga-PSMA on the diagnostic PET/MRI examination in the screening part of the study are eligible for a standard of 3 cycles, with a possible extension to maximum number of 6 cycles, of 177Lu-PSMA radionuclide therapy sessions. SPECT/CT will be performed after each cycle of treatment for dosimetry calculations, while 68Ga-PSMA PET/MRI, quality-of-life schemes and clinical examinations will be used to monitor therapeutic effects during the therapy cycles and up to 1.5 year after treatment initiation. The main endpoints of the study are progression-free survival and overall survival.

Radiation: 177Lu-PSMA I&T; Patients demonstrating a high tumor uptake of 68Ga-PSMA on the diagnostic PET/MRI examination in the screening part of the study are eligible for a standard of 3 cycles, with a possible extension to maximum number of 6 cycles, of 177Lu-PSMA radionuclide therapy sessions. SPECT/CT will be performed after each cycle of treatment for dosimetry calculations, while 68Ga-PSMA PET/MRI, quality-of-life schemes and clinical examinations will be used to monitor therapeutic effects during the therapy cycles and up to 1.5 year after treatment initiation. The main endpoints of the study are progression-free survival and overall survival.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Type, frequency and severity of adverse events assessed with the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	6 months after end of therapy
Evaluation of efficacy of 177Lu- PSMA	Progression free survival (6 months) determined from date of commencement of 177Lu-PSMA therapy	6 months after commencement of therapy
Evaluation of efficacy of 177Lu- PSMA	Overall survival (1 year) determined from date of commencement of 177Lu-PSMA therapy	1 year after commencement of therapy
Adverse events	Change in score in the modified RAI-6 questionnaire.	Day 1 and 6 months after end of therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate radiation dose to tumor and critical organs	Calculation of absorbed doses to the tumor and kidneys, parotid glands, sublingual glands, submandibular glands, lacrimal glands, liver, spleen and red marrow for each therapy cycle as well as accumulated doses for all therapy cycles.	7 days after commencement of therapy
Tumor response	Tumor responses as assessed by contrast enhanced MRI according to response assessment in neuro oncology (RANO) criteria (50) (Attachment 3) and volume measurements.	8 weeks
Nano score	Neurologic exam (nano score)	8 weeks
Health related quality of life	Health-related quality of life EQ-5D scores	8 weeks
Karnofsky performance status	Karnofsky performance status	8 weeks
PSMA uptake versus progression free survival	Correlate 68Ga-PSMA uptake (SUV) to overall and image-based progression free survival.	8 weeks
Pretherapeutic PSMA uptake versus accumulated doses	Evaluate the possible correlation between the pretherapeutic uptake of 68Ga -PSMA (SUV) in tumors and salivary glands to accumulated doses received from therapeutic 177Lu-PSMA.	8 weeks
Tumor-to-parotis ratio threshold for indication of 177Lu-PSMA therapy	Establish an appropriate indication for 177Lu-PSMA therapy by measuring tumor:parotis-ratios in 68Ga-PSMA PET scans.	8 weeks
Change in PSMA uptake during treatment period versus overall survival	Measure changes in uptake (SUV) of 68Ga-PSMA during the treatment period and correlate to overall survival in order to evaluate the role of post-therapeutic 68Ga-PSMA PET in monitoring disease.	8 weeks

Collaborators and Investigators

• Sponsor: St. Olavs Hospital
• Collaborators: Norwegian University of Science and Technology
• Investigators: Principal Investigator: Tora Solheim, MD/PhD, St. Olavs hospital/NTNU

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: November 15, 2022
• First Submitted That Met QC Criteria: December 1, 2022
• First Posted (Actual): December 9, 2022

Study Record Updates

• Last Update Posted (Estimated): June 5, 2025
• Last Update Submitted That Met QC Criteria: June 4, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma
• Other Study ID Numbers: 412811

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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