Clinical trial NCT05644080: 68Ga/177Lu-PSMA Theranostics in Recurrent Grade 3 and Grade 4 Glioma
Official title: 68Ga/177Lu-PSMA Theranostics in Recurrent Grade 3 and Grade 4 Glioma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: High Grade Glioma
Lead sponsor: St. Olavs Hospital
Sponsor class: OTHER
Collaborators: name: Norwegian University of Science and Technology
First posted: 2022-12-09
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Patients with recurrent grade 3 and grade 4 glioma will be recruited for treatment with 177Lu-PSMA.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of adverse events
timeFrame: 6 months after end of therapy
measure: Evaluation of efficacy of 177Lu- PSMA
timeFrame: 6 months after commencement of therapy
measure: Evaluation of efficacy of 177Lu- PSMA
timeFrame: 1 year after commencement of therapy
measure: Adverse events
timeFrame: Day 1 and 6 months after end of therapy
Secondary outcomes:
measure: Evaluate radiation dose to tumor and critical organs
timeFrame: 7 days after commencement of therapy
measure: Tumor response
timeFrame: 8 weeks
measure: Nano score
timeFrame: 8 weeks
measure: Health related quality of life
timeFrame: 8 weeks
measure: Karnofsky performance status
timeFrame: 8 weeks
measure: PSMA uptake versus progression free survival
timeFrame: 8 weeks
measure: Pretherapeutic PSMA uptake versus accumulated doses
timeFrame: 8 weeks
measure: Tumor-to-parotis ratio threshold for indication of 177Lu-PSMA therapy
timeFrame: 8 weeks
measure: Change in PSMA uptake during treatment period versus overall survival
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Trondheim
country: Norway
facility: St. Olavs hospital
Study officials:
affiliation: St. Olavs hospital/NTNU
name: Tora Solheim, MD/PhD
role: PRINCIPAL_INVESTIGATOR
References: