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Trial registered on ANZCTR


Registration number
ACTRN12625000934448
Ethics application status
Approved
Date submitted
9/07/2025
Date registered
28/08/2025
Date last updated
28/08/2025
Date data sharing statement initially provided
28/08/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase III Study of TLX101-Tx Plus Standard of Care (SoC) Versus SoC Alone for the Treatment of Patients With Recurrent Glioblastoma ( IPAX-3 ) - Part 1
Scientific title
A Global, Multicenter, Prospective, Controlled, Open-Label Pivotal Study of Iodofalan (131I) Solution for Injection (TLX101-Tx) Plus Lomustine Versus Lomustine Alone in Patients With Radiographically Confirmed Recurrent Glioblastoma at First Recurrence (IPAX-3) - Part 1
Secondary ID [1] 314868 0
131I-TLX-101-003
Universal Trial Number (UTN)
Trial acronym
Linked study record
A Phase 1 study has been conducted in recurrent Glioblastoma (NCT03849105), and a sister Phase 1 study conducted in Newly diagnosed Glioblastoma (NCT05450744) is currently dosing patients using the same Investigational product.

Health condition
Health condition(s) or problem(s) studied:
Neoplastic disease 338152 0
Glioblastoma 338258 0
Condition category
Condition code
Cancer 334435 334435 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Lomustine is provided as a oral capsule (typically 10 mg and 40 mg).

In Part 1: Safety and Dosimetry Lead-In, eligible patients will receive the following treatment:
Arm A:
o Lomustine will be prescribed at 90 mg/m2 in a 42-day cycle starting on Day 1 for all dose levels (DLA 0, -1, -2) within Arm A.
o TLX101-Tx will be administered at total prescribed activity according to the DL delivered in 3 equal doses on Day 1, Day 43, and Day 85 of chemotherapy
DLA 0: 12 GBq (324 mCi) total activity in 3x 4 GBq (108 mCi) fractions
DLA -1: 9 GBq (243 mCi) total activity in 3x 3 GBq (81 mCi) fractions
DLA -2: 6 GBq (162 mCi) total activity in 3x 2 GBq (54 mCi) fractions
Arm B:
o Lomustine will be prescribed at 70 mg/m2 in 42-day cycle starting on Day 1 for all dose levels (DLB 0, -1, -2) within Arm B.
o TLX101-Tx will be administered at total prescribed activity according to the DL delivered in 3 equal doses on Day 1, Day 43, and Day 85 of chemotherapy
DLB 0: 12 GBq (324 mCi) total activity in 3x 4 GBq (108 mCi) fractions
DLB -1: 9 GBq (243 mCi) total activity in 3x 3 GBq (81 mCi) fractions
DLB -2: 6 GBq (162 mCi) total activity in 3x 2 GBq (54 mCi) fractions
Intervention code [1] 331477 0
Treatment: Drugs
Comparator / control treatment
Arm C:
o TLX101-Tx monotherapy will be administered at total prescribed activity according to the DL delivered in 3 equal doses on Day 1, Day 29, and Day 57
DLC 0: 12 GBq (324 mCi) total activity in 3x 4 GBq (108 mCi) fractions
DLC -1: 9 GBq (243 mCi) total activity in 3x 3 GBq (81 mCi) fractions
DLC -2: 6 GBq (162 mCi) total activity in 3x 2 GBq (54 mCi) fractions
Control group
Dose comparison

Outcomes
Primary outcome [1] 342130 0
To determine the maximum tolerated dose (MTD) of TLX101-Tx plus lomustine (or TLX101-Tx as a monotherapy)
Timepoint [1] 342130 0
Daily assessment of TEAE is from enrolment to the end of treatment at around 12 weeks
Primary outcome [2] 342226 0
Dose optimization and determine the recommended phase III dose (RP3D).
Timepoint [2] 342226 0
Assessment from enrolment to 85 Days of treatment - SPECT/CT scans for image based dosimetry are conducted at Day 0 (enrolment) and Day 85.
Primary outcome [3] 342227 0
To determine the safety, tolerability, and the recommended Phase 3 study dose of TLX101-Tx in combination with lomustine (or TLX101-Tx as a monotherapy) in patients with confirmed first recurrence of glioblastoma.
Timepoint [3] 342227 0
Assessment of TEAE is from enrolment to 85 Days of treatment - there are Nine visits during this 85 day period. This will include Screening Visit 1 (up to 21 days prior to first dose), D0 (Visit 2 - Dose 1 TLX101-Tx), D1 / Visit 3, Day 28 / Visit4, D35 / Visit5, Day 43/ Visit6 (Dose 2 TLX101-Tx), Day 70 / Visit 7, Day 77 / Visit 8 and Day 85 /Visit 9 (Dose 3 TLX101-Tx). This is followed by Lomustine Maintenance Therapy (42 day cycle) and Follow-up every 12 weeks.
Secondary outcome [1] 449712 0
Characterize Blood Pharmacokinetics of TLX101-Tx
Timepoint [1] 449712 0
Blood sampling for dosimetry through 168 hours after the first and third TLX101-Tx administration - SPECT/CT imaging and blood sampling blood-based radiation absorbed dose assessments at pre-dose -10±5 min (blood sample only) and at post-dose timepoints at approximately at 10±5 min (blood sample only), 2±1 hours (blood sample only), 4±2 hours (or longer to ensure that camera count rate is below 70,000 CPS), 24±4 hours, 48±8 hours, 96±24 hours, and 168±48 hours.
Secondary outcome [2] 450010 0
Radiation Dosimetry - we will measure how much radiation from TLX101-Tx reaches the tumor and the bone marrow.
Timepoint [2] 450010 0
From enrollment to the end of treatment at around 12 weeks - Cerebral [18F]FET PET during Screening less than or equal to 14 days post-surgical re-resection of tumor at time of progression but no more than 14 days before planned treatment commencement. MRI with contrast to be performed as part of the screening visit if prior MRI with contrast is performed more than 28 days from the planned treatment commencement. Follow-up MRI with contrast (RANO 2.0) and follow-up cerebral [18F]FET PET (PET RANO 1.0) every 8 weeks ±7 days from each other
Secondary outcome [3] 450011 0
Characterise the Urinary excretion of TLX101
Timepoint [3] 450011 0
Urine samples will be collected at 0 – 4 hours, 4 – 8 hours, 8-12 hours, 12-24 hours, 24-48 hours and 48-72 hours post each dose of TLX101. Urinary excretion of total radioactivity will be evaluated.to characterize drug elimination. The following PK parameters will be determined based on urine radioactivity measurements: Cumulative Urinary Excretion (%Dose Excreted): Fraction of administered radioactivity excreted in urine over time; Ae(t): Amount of radioactivity excreted over a specific time interval; Ae8: Total cumulative amount of radioactivity excreted in urine from dosing until the last measurable time point; Renal Clearance (CLr): Calculated as Ae(t)/AUCplasma, where AUCplasma is the plasma area under the curve for total radioactivity; Fraction of Dose Excreted in Urine (fe): Percentage of the administered dose recovered in urine
Secondary outcome [4] 450871 0
Primary Outcome: To determine the recommended dose of TLX101-Tx plus lomustine (or TLX101-Tx as a monotherapy)
Timepoint [4] 450871 0
Daily assessment of TEAE is from enrolment to the end of treatment at around 12 weeks

Eligibility
Key inclusion criteria
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: a. Any systemic antineoplastic treatment other than nitroureas b. Tumor-treating fields c. 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, with a TBRmax greater than or equal to 2.3, 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 (TBRmax greater than or equal to 2.3) 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 greater than or equal to 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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 greater than 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/09/2025
Actual
Date of last participant enrolment
Anticipated
30/07/2027
Actual
Date of last data collection
Anticipated
30/11/2027
Actual
Sample size
Target
18
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment outside Australia
Country [1] 27201 0
Austria
State/province [1] 27201 0
Country [2] 27202 0
Netherlands
State/province [2] 27202 0
Country [3] 27203 0
United States of America
State/province [3] 27203 0

Funding & Sponsors
Funding source category [1] 319427 0
Commercial sector/Industry
Name [1] 319427 0
Telix Pharmaceuticals
Country [1] 319427 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Telix Pharmaceuticals
Address
Country
Australia
Secondary sponsor category [1] 321917 0
None
Name [1] 321917 0
Address [1] 321917 0
Country [1] 321917 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 317998 0
St Vincent’s Hospital Human Research Ethics Committee
Ethics committee address [1] 317998 0
Ethics committee country [1] 317998 0
Australia
Date submitted for ethics approval [1] 317998 0
23/05/2025
Approval date [1] 317998 0
03/07/2025
Ethics approval number [1] 317998 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 142826 0
Dr Wade Pullin
Address 142826 0
Gold Coast University Hospital, 1 Hospital Boulevard, Southport, QLD 4215
Country 142826 0
Australia
Phone 142826 0
+61 7 56872702
Fax 142826 0
Email 142826 0
[email protected]
Contact person for public queries
Name 142827 0
Danielle Miller
Address 142827 0
Gold Coast University Hospital, 1 Hospital Boulevard, Southport, QLD 4215
Country 142827 0
Australia
Phone 142827 0
+61 7 56876395
Fax 142827 0
Email 142827 0
[email protected]
Contact person for scientific queries
Name 142828 0
Wade Pullin
Address 142828 0
Gold Coast University Hospital, 1 Hospital Boulevard, Southport, QLD 4215
Country 142828 0
Australia
Phone 142828 0
+61 7 56872702
Fax 142828 0
Email 142828 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.