2nd line therapy of recurrent GBM (Glioblastoma multiforme), scheduled for repeat XRT.
Conditions
Interventions
Product Name: [131I]-L-4-iodophenylalanine
Pharmaceutical Form: Infusion
INN or Proposed INN: [131I]-L-4-iodophenylalanine
Current Sponsor code: 131 I-IPA
Concentration unit: GBq gigabecquerel(s)
Conc
Sponsors
TELIX International Pty Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Previously confirmed histological diagnosis of GBM, with current clinical or imaging evidence for first recurrence according to modified RANO criteria (2017). History of GBM standard therapy (debulking surgery, followed by radio-chemotherapy (50–60 Gy in 2 Gy fractions, temozolomide) 2. Interval since end of 1st line XRT =6 months 3. Amino acid-based molecular imaging (preferably 18F-FET-PETor 11C-methionine, as institutionally established) indicating pathologically increased amino acid uptake inside or in the vicinity of the tumour, clearly discernible from background activity. 4. Current indication for repeat radiation therapy as discussed at the multidisciplinary neuro-oncological tumour board meeting, planned as standard fractionated dose schedule (18*2 Gy) 5. Gross tumour volume (GTV) of up to 4.8 cm diameter, clinical target volume (CTV) 0.5 cm margin and planning target volume (PTV) =0.5 cm margin 6. Male or female =18 years of age. 7. Karnofsky performance status (KPS) =70. Life expectancy of at least 16 weeks. 8. Haematological, liver and renal function test results as follows: • WBC: >3*109/L • Haemoglobin >80 g/L • PLT >100*109/L • ALT, ALP, AST: =5 times upper international limit of normal (UILN) • Bilirubin =3 times UILN • Serum creatinine: within normal limits or =65 years) yes F.1.3.1 Number of subjects for this age range 14
Exclusion criteria
Exclusion criteria: 1. Primary XRT dose >60 Gy 2. Doses to organs at risk defined by Yasar and Tugrul (2005) exceeded or reached by prior radiation therapy; e.g. cumulative total dose on the optical chiasm >54 Gy for 2 Gy/fraction, alpha/beta=2 3. Multifocal distant recurrence, defined as tumour lesion outside the primary XRT field, as evidenced by amino acid-based PET imaging 4. Prior treatment with brachytherapy 5. Prior treatment with bevacizumab 6. History or evidence of delayed-type hypersensitivity (DTH)-dependent chronic infection (e.g. tuberculosis, systemic fungal or parasitic infection), potentially exacerbating under systemic corticoid therapy 7. Localisation of tumour related to brain stem or axis, unless sufficient reserve capacity (e.g. remnant resection cavity, marked atrophy) to accommodate possible post–procedural tissue reactions, or pre-therapeutic consent for emergency trepanation 8. Haemostaseologic conditions, precluding catheterisation or invasive procedures 9. Clinically significant illness or clinically relevant trauma within 2 weeks before the administration of the investigational product 10. Known impairment of liver or kidney function or known liver or kidney disease, such as hepatitis, cirrhosis, renal failure 11. Known human immunodeficiency virus (HIV) positive serology or chronically active hepatitis B or C 12. Ongoing toxicity > grade 2 NCI-CTC (version 4.03) from previous standard or investigational therapies 13. Administration of another investigational medicinal product within 90 days prior to screening 14. Expected non-compliance with longer-term admission at isolated nuclear medicine ward 15. In pre-menopausal women: Pregnant as evidenced by a positive pregnancy test, or breast-feeding 16. Patients with known phenylketonuria
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety and tolerability of intravenous 131I-IPA administered concomitantly to 2nd line XRT in recurrent GBM;Secondary Objective: 1. To assess the maximum tolerated dose (MTD) of 131I -IPA administered concomitantly to 2nd line XRT in recurrent GBM 2. To evaluate the feasibility of a fractionated administration of 131I-IPA 3. To evaluate the radiation absorbed dose to tumour from 131I-IPA 4. To explore the antineoplastic effect of 131I-IPA + XRT combination therapy 5. To explore a possible influence of MGMT promoter methylation status on the biological response to 131I-IPA + XRT combination therapy 6. To explore the occurrence and frequency of pseudo-progression (PP) in response to 131I-IPA + XRT combination therapy 7. To explore the cognitive function before, during and after therapy ;Primary end point(s): a) Safety as assessed by the frequency of occurrence and severity of abnormal findings in safety investigations (physical examination, vital signs, 12-lead ECG, clinical laboratory, adverse events, concomitant medication) b) Tolerability as assessed by Health-Related Quality of Life (HRQOL) total scores on European Organisation for Research and Treatment of Cancer – EORTC QLQ-C30 and EORTC-BN20 questionnaires (Aaronson et al. 1993; Osoba et al. 1996) ;Timepoint(s) of evaluation of this end point: 3 monthly scans for 12 months. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Whole body biodistribution and dosimetry (safety dosimetry) a) Residence times for discernible organs (MBq*h) b) Organ and whole body absorbed radiation doses (µSv/MBq) Tumour dosimetry of 131I-IPA following systemic administration (therapeutic dosimetry) a) Cmax (maximum activity concentration in tumour Bq/cm³) b) tmax (time point of maximum activity concentration in tumour) c) TAC (time activity curve) for metabolic tumour volume (MTV) defined by BL 18F-FET PET and 131I-IPA SPECT d) Tumour absorbed radiation dose (µGy/MBq) Efficacy a) Radiological and clinical response according to the current RANO criteria b) Metabolic tumour response: SUVmax, SUVmean, MTV c) Survival: PFS, OS Dosing schedule a) Proportion of subjects (%) with reduction morphological, contrast, and metabolic tumour volume reduction, analysed by dose level and dosing schedule b) Extent of morphological, contrast, and metabolic tumour volume reduction (mL), analysed by dose level and dosing schedule c) Duration (months) of morphological, contrast, and metabolic tumour volume reduction, analysed by dose level and dosing schedule ;Timepoint(s) of evaluation of this end point: Endpoint 1: Evaluated on Patient by Patient Basis by an analysis of Adverse events Endpoint 2: Evaluated on Patient by Patient Basis by an analysis of Adverse events Endpoint 3: conducted by Imaging, four images to evaluate uptake excretion to determine the radiation absorbed dose in the Tumor Endpoint 4: Analyzing functional and metabolic response based on the 3 monthly image aqquisition Endpoint 5: Remote analysis after end of study Endpoint 6: Analyzing functional and metabolic response based on the 3 monthly image aqquisition Endpoint 7: Quarterly analysis of Patient completed and physician completed Quality of Life documents | — |
Countries
Australia, Austria, Belgium, Netherlands
Contacts
Public ContactClinical Informations
ABX-CRO advanced pharmaceutical services GmbH
Outcome results
None listed