Neoplastic DiseaseGlioblastomaGlioblastoma (GBM)Glioblastoma MultiformGlioblastoma Multiforme, AdultGlioblastoma Multiforme (GBM) WHO Grade IV
Investigational drug(s) / intervention(s)
TLX-101-Tx + LomustineTLX101-Tx
TLX-101-Tx + Lomustine: Combination therapy with TLX-101-Tx + Lomustine
TLX101-Tx: TLX101-Tx
Study summary
This global clinical trial which evaluates the efficacy and safety of TLX101-Tx, an investigational radiopharmaceutical therapy, in combination with lomustine versus lomustine alone in adult patients with first recurrence of glioblastoma. TLX101-Tx delivers targeted radiation to glioblastoma cells. The trial is conducted in two parts: Part 1 assesses safety and radiation dosing; Part 2 is a randomized comparison of the combination therapy against standard care.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
1. Previously confirmed neuropathological diagnosis of glioblastoma, IDH-wildtype according to the WHO 2021 classification.
2. Radiographic evidence of first recurrence or progressive glioblastoma according to RANO 2.0 criteria after first-line treatment with biopsy or maximal safe resection and standard radiotherapy or chemoradiotherapy having occurred at least 3 months after the end of prior radiotherapy. Prior first-line therapy may include a combination of:
1. Any systemic antineoplastic treatment other than nitroureas
2. Tumor-treating fields
3. Conventionally fractionated or abbreviated (minimum 15 fractions) radiotherapy
3. Increased \[18F\]\]FET PET tracer uptake inside or in the vicinity of tumor. Specifically, amino acid-based molecular imaging using \[18F\]FET PET will be evaluated following co-registration with MRI. The allocated physician/reader will assess whether the observed pathologically increased amino acid uptake is located within the tumor or in the vicinity. This determination will serve as a guidance to confirm whether the uptake is tumor-associated. The uptake must be clearly discernible from background activity and measurable per PET RANO 1.0 criteria, as determined by central review.
4. Tumor debulking for recurrent, progressive disease is allowed. The patient must have post-surgical (4-6 weeks) radiographic evidence for residual tumor according to RANO 2.0 with increased \[18F\] FET PET uptake and measurable disease according to PET RANO 1.0.
5. 18 years or older
6. Have the capacity to understand the study and be willing to comply with all protocol requirements.
7. Must have an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-2 or KPS≥70
8. Patients on stable, not increasing dose of steroids in the previous 7 days can be included in the study
9. Adequate hematological, liver and renal function at the time of screening.
10. Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose of investigational drug product; must not be breast-feeding; and must agree to use a highly effective method of contraception during treatment and for 6 months following last dose of investigational product.
11. Male patients must agree to use condoms during sex during the treatment period and for 3 months after the last dose of the investigational drug product and must not make semen donations during treatment and for 6 months following last dose of investigational drug product. For male patients with female partners of childbearing potential, females must agree to use a highly effective method of contraception during the treatment period and for 6 months following last dose of investigational drug product.
Exclusion Criteria:
1. Prior course with external beam radiation to the brain in the past 3 months. Prior treatment with brachytherapy in the brain.
2. Treatment with bevacizumab within the prior 6 weeks.
3. Known contraindication to imaging tracer or any product of contrast media and MRI contraindications including implanted medical devices. Unable to lie still for at least 20 min or the duration of the MRI and PET imaging or the need for general anesthesia as part of the imaging procedure.
4. History or evidence of delayed-type hypersensitivity-dependent chronic infection (ie, tuberculosis, systemic fungal or parasitic infection).
5. Radiographic progression based on RANO 2.0 associated with clinical deterioration and life expectancy less than 3 months.
6. Hemostaseologic conditions, precluding catheterization or invasive procedures.
7. Clinically significant illness or clinically relevant trauma within 2 weeks before the administration of the investigational product.
8. Known liver or kidney disease, such as hepatitis, cirrhosis, renal failure.
9. Severe chronic or active infections (including active tuberculosis, hepatitis B virus, or hepatitis C virus infection) requiring systemic therapy.
10. Ongoing toxicity \> Grade 2 NCI-CTCAE (version 5.0) from previous standard or investigational therapies.
11. Administration of another investigational product within 90 days prior to screening.
12. Expected non-compliance with longer-term admission at isolated nuclear medicine ward per regional regulations.
13. Inability to complete the needed investigational and standard imaging examinations due to any reason (ie, severe claustrophobia, inability to lie still for the entire imaging time).
14. Patients with known phenylketonuria.
15. Presence of any other condition that may increase the risk associated with study participation or interfere with the interpretation of study results, and, in the opinion of the study investigator, would make the patient inappropriate for entry into the study.
Primary outcome measure(s)
Safety and Tolerability — Through study completion, an average of 2 years Assessing TEAEs type according to MedDRA (Medical Dictionary for Regulatory Activities), frequency, severity according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V5.0, seriousness, and relationship of study treatment will be assessed. Laboratory abnormalities will be assessed according to the NCI CTCAE V5.0.
Dose Optimization — Through study completion, an average of 2 years Part 1 of the study is being done to identify the best dose to use for Part 2 of the study
Trial sites (9)
Facility
City
Region
Status
Gold Coast University Hospital
Gold Coast
Queensland
Recruiting
Austin Health
Melbourne
Victoria
Recruiting
Sir Charles Gairdner Hospital
Perth
Western Australia
Recruiting
Royal Adelaide Hospital
Adelaide
Australia
Not Yet Recruiting
Johannes Kepler University
Linz
Austria
Recruiting
UZ Leuven
Leuven
Belgium
Recruiting
Chu of Liège
Liège
Belgium
Recruiting
The Netherlands Cancer Institute (NKI)
Amsterdam
Netherlands
Not Yet Recruiting
UMC Utrecht
Utrecht
Netherlands
Recruiting
More Telix Pharmaceuticals (Innovations) Pty Limited trials in Australia
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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