Not Yet RecruitingPhase 3ACTRN12625000934448

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

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

Sponsor

Telix Pharmaceuticals

Enrollment

18 participants

Start Date

Sep 1, 2025

Study Type

Interventional

Conditions

Glioblastoma

Summary

This global clinical trial which evaluates the efficacy and safety of TLX101-Tx, a potential new treatment for patients with recurrent glioblastoma, The purpose of the study is to assess the safety and tolerability of TLX101-Tx given alone or in combination with standard care chemotherapy, called lomustine. Between 6 to 18 patients are expected to be enrolled. Who is it for? To be eligible for this study you must be 18 years or older with a confirmed diagnosis of IDH-wildtype glioblastoma showing first recurrence or progression after standard first-line treatment. You must have measurable disease with increased [18F]FET PET uptake, adequate organ function, ECOG performance status of 0–2, and be able to comply with study requirements. Stable steroid use and appropriate contraception measures are also required. Study details If you participate, you will be assigned to a study arm (a group of patients receiving the same treatment), to test different doses of the study drug either alone or in combination with lomustine. Your time on this study will be about 52 weeks. You will be required to return to the study site for multiple visits over the course of the study. This study is divided into four periods. Depending on which arm or study you are assigned, your schedule may look different. Screening period (up to 21 days) Treatment period (up to 127 days) Maintenance period Follow up period (every 12 weeks) This study may have up to three arms. All study participants will receive the study drug. However, depending on when you enter the study, you could be assigned to a study arm without lomustine. Arm A: Receive TLX101-Tx and lomustine at 90 mg/m2 in combination. Then lomustine alone in Maintenance Therapy. Arm B: Receive TLX101-Tx and lomustine at 70 mg/m2 in combination. Then lomustine alone in Maintenance Therapy. Arm C: Receives TLX101-Tx alone. Then lomustine alone in Maintenance Therapy. This arm will only open when Arms A and B are closed. During the Treatment Period, you will need to attend the study site for at least 8 visits over 12 weeks. Your study doctor will explain what you must do, and which tests you will have during the study. Each visit may be different in length depending on what tests will be done and will take between 2-3 hours. TLX101-Tx will be given as an intravenous infusion (IV), which means it will be injected through a vein in your arm. You will receive 3 equal doses over 85 days. If you are assigned to Arm A or B, you would also take lomustine by mouth on the same day (Days 1, 43 and 85). If you are assigned to Arm C, you will receive only TLX101-Tx on Days 1, 29 and 57. During the study visits, you will have the required tests and procedures as described by a protocol and will include: Physical examination, Measurement of vital signs, Medications Review, Blood tests, Dosimetry Imaging (SPECT/CT scans), Tumour Assessment (MRI and PET scans), Urine Test, ECG, QOL and Neurological assessments

Eligibility

Sex: Both males and femalesMin Age: 18 Yearss

Inclusion Criteria11

Previously confirmed neuropathological diagnosis of glioblastoma, IDH-wildtype according to the WHO 2021 classification.
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
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.
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.
18 years or older
Have the capacity to understand the study and be willing to comply with all protocol requirements.
Must have an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0–2 or KPS greater than or equal to 70
Patients on stable, not increasing dose of steroids in the previous 7 days can be included in the study
Adequate hematological, liver and renal function at the time of screening.
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.
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 Criteria15

Prior course with external beam radiation to the brain in the past 3 months. Prior treatment with brachytherapy in the brain.
Treatment with bevacizumab within the prior 6 weeks.
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.
History or evidence of delayed-type hypersensitivity-dependent chronic infection (ie, tuberculosis, systemic fungal or parasitic infection).
Radiographic progression based on RANO 2.0 associated with clinical deterioration and life expectancy less than 3 months.
Hemostaseologic conditions, precluding catheterization or invasive procedures.
Clinically significant illness or clinically relevant trauma within 2 weeks before the administration of the investigational product.
Known liver or kidney disease, such as hepatitis, cirrhosis, renal failure.
Severe chronic or active infections (including active tuberculosis, hepatitis B virus, or hepatitis C virus infection) requiring systemic therapy.
Ongoing toxicity greater than Grade 2 NCI-CTCAE (version 5.0) from previous standard or investigational therapies.
Administration of another investigational product within 90 days prior to screening.
Expected non-compliance with longer-term admission at isolated nuclear medicine ward per regional regulations.
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).
Patients with known phenylketonuria.
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.

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Interventions

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

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