Patients with confirmed recurrent grade 3 and grade 4 glioma
Conditions
Interventions
Product Name: [177Lu]Lu-PSMA-I&T
Pharmaceutical Form: Solution for injection
Sponsors
Norwegian University of Science and Technology
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria - screening • A previous diagnosis of histologically confirmed WHO grade 3 or grade 4 glioma • Radiologically (MRI) confirmed tumour 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) Inclusion criteria – 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. • Patient accept not to receive any other tumor directed treatment before 8 weeks after each 177Lu-PSMA injection. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 5 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: Exclusion Criteria -screening • 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 • 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. Exclusion Criteria – therapy • Concurrent investigational drugs or experimental therapy must be stopped at least 4 weeks prior to study entry • Unwilling to accept potential challenge with xerostomia
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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. Primary: •Assessment of safety and tolerability of 177Lu- PSMA •Assessment of efficacy of 177Lu- PSMA in the treatment of patients with recurrent or progressed grade 3 and grade 4 glioma after treatment with 177Lu- PSMA ;Secondary Objective: Key secondary objectives •Perform organ/tumor dosimetry in patients receiving targeted radionuclide therapy with 177Lu- PSMA •Document indicators of efficacy of 177Lu-PSMA with MRI and quality of life •Describe biomarkers in imaging, dosimetry and tumor tissue that correlate with treatment responses •Describe diagnostic properties of 68Ga-PSMA: oCan the pre-therapeutic uptake of 68Ga -PSMA predict overall and image-based progression free survival? oCan the pretherapeutic uptake of 68Ga -PSMA indicate tumor-to-critical-organ doses of therapeutic 177Lu-PSMA? oWhich TBR and tumor:parotis-ratio are appropriate indication for 177Lu-PSMA-therapy? oWhat is the role of post-therapeutic 68Ga-PSMA- PET in monitor disease? ;Primary end point(s): Primary •Assessment of safety and tolerability: oAssessed with Toxicity assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (Attachment 1) and a modified RAI-6 questionnaire (Attachment 2). •Assessment of efficacy of 177Lu- PSMA: oProgression free survival (6 months) and overall survival (1 year) determined from date of commencement of 177Lu-PSMA therapy ;Timepoint(s) of evaluation of this end point: During each cycle of treatment safety and tolerability will be monitored on days 1, 3, 7 and 28 and after 8 weeks. Progression free survival will be evaluated at 6 months after initiation of treatment and overall surviv | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary • Organ and tumor dosimetry of 177Lu-PSMA therapy • Assessment of efficacy: o Tumour responses as assessed by contrast enhanced MRI according to response assessment in neuro oncology (RANO) criteria (Attachment 3) and volume measurements. o Neurologic exam (nano score) o Health-related quality of life EQ-5D scores (Attachment 4) o Karnofsky ;Timepoint(s) of evaluation of this end point: Dosimetry will be calculated 1 week after each cycle of therapy. Assessment of efficacy will be evaluated when the follow-up period is completed, 12 months after initiation of therapy. | — |
Countries
Norway
Contacts
Public ContactTora Skeidsvoll Solheim
Norwegian University of Science and Technology
Outcome results
None listed