131I-IPA and Concurrent XRT in Recurrent GBM

NCT03849105 | Completed Phase 1

• 1 other identifier: 131I-IPA-TLX-101-001
• Study Type: interventional
• Target: 10
• Locations: 2 countries
• Sites: 3

Brief Summary

A multi-centre, open-label, single-arm, dose-finding phase I/II study to evaluate safety, tolerability, dosing schedule, and preliminary efficacy of carrier-added 4-L-\[131I\]iodo-phenylalanine (131I-IPA), administered as single or repetitive injections in patients with recurrent glioblastoma multiforme (GBM), concomitantly to 2nd line external radiation therapy (XRT) - IPAX-1

Conditions

Glioblastoma Multiforme

Keywords

glioblastoma multiforme (GBM),; External Radiotherapy; 131I-IPA

Outcome Measures

Primary Outcomes (6)

• Safety and tolerability parameter Adverse Events

  Treatment-related adverse events according to NCI-CTCAE v 4.03 criteria will be captured and evaluated for each patient

  From first administration of 131I-IPA until 12 months after first administration

• Safety parameter heart rate

  Frequency of occurrence and severity of abnormal findings as measured by beats per minute

  From first administration of 131I-IPA until 12 months after first administration

• Safety parameter blood pressure

  Frequency of occurrence and severity of abnormal findings as measured by mmHg

  From first administration of 131I-IPA until 12 months after first administration

• Safety parameter Liver function test

  This outcome will be measured on all patients with treatment-related adverse events based on criteria as determined by the NCI CTCAE v 5.0 criteria. Results will be assessed by number of participants with abnormal laboratory values.

  From first administration of 131I-IPA until 12 months after first administration

• Safety parameter Renal function test

  This outcome will be measured on all patients with treatment-related adverse events based on criteria as determined by the NCI CTCAE v 5.0 criteria. Results will be assessed by number of participants with abnormal laboratory values.

  From first administration of 131I-IPA until 12 months after first administration

• Safety parameter Full Blood Count

  This outcome will be measured on all patients with treatment-related adverse events based on criteria as determined by the NCI CTCAE v 5.0 criteria. Results will be assessed by number of participants with abnormal laboratory values.

  From first administration of 131I-IPA until 12 months after first administration

Secondary Outcomes (9)

• To evaluate the maximum tolerated dose (MTD) of 131I -IPA administered concomitantly to 2nd line XRT in recurrent GBM 2

  Evaluation of patient up to 30 days after completion of study therapy

• To evaluate the efficacy of a fractionated administration of 131I-IPA

  Up to 6 months after completion of study therapy

• Dosimetry

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months

• Dosimetry

  Up to 30 days after completion of study therapy

• To explore the antineoplastic effect of 131I-IPA + XRT combination therapy

  Commencing just prior to first administration of 131I-IPA until 12 months from time of first therapeutic administration

Study Arms (4)

Single administration of 131I-IPA (1f group)

EXPERIMENTAL

Study participants with GBM receive a single administration of 4-L-\[131I\]iodo-phenylalanine (131I-IPA), followed by 18 cycles of external radiotherapy, each cycle being of 2 Gy.

Radiation: 4-L-[131I]iodo-phenylalanine (131I-IPA)

Three administrations of 131I-IPA (3f-parallel group)

EXPERIMENTAL

Study participants will be administered in 2GBq in 3 fractions corresponding to ⅓ full dose activity (0.67 GBq for the 2.0 GBq dose level). The 1st fraction of 131I-IPA will be administered as above, 1- 3 days prior to 1st XRT. The 2nd and 3rd 131I-IPA fractions will be administered after 5-9 XRT fractions (subject to investigator's discretion and day of IMP administration) following the previous 131I-IPA fraction. The remainder of XRT fractions will be given following the 3rd 131I-IPA fraction.

Radiation: 4-L-[131I]iodo-phenylalanine (131I-IPA)

Three administrations of 131I-IPA (3f-sequential group)

EXPERIMENTAL

Study participants will be administered in 2GBq in 3 fractions corresponding to ⅓ full dose activity (0.67 GBq for the 2.0 GBq dose level). The 1st fraction of 131I-IPA will be administered as above 1- 3 days prior to 1st XRT. The 2nd 131I-IPA fraction will be administered after all 18 XRT fractions have been completed, and the 3rd 131I-IPA fraction will be administered 1 week after the 2nd 131I-IPA fraction.

Radiation: 4-L-[131I]iodo-phenylalanine (131I-IPA)

Dose escalation of fractionated dosing

EXPERIMENTAL

Dose escalation will be made in steps of 2.0 GBq, i.e. 4.0 (3\*1.33 GBq), 6.0 GBq (3\*2.0 GBq), up to 8.0 GBq (3\*2.67 GBq) until the maximum tolerated dose (MTD) is reached, using cohorts of N=3 patients.

Radiation: 4-L-[131I]iodo-phenylalanine (131I-IPA)

Interventions

4-L-[131I]iodo-phenylalanine (131I-IPA) RADIATION

Study participants will receive by intravenous infusion an escalating activity of 4-L-\[131I\]iodo-phenylalanine (131I-IPA). Additional therapy is received in the form of externally administered radiotherapy

Also known as: external radiotherapy

Dose escalation of fractionated dosing; Single administration of 131I-IPA (1f group); Three administrations of 131I-IPA (3f-parallel group); Three administrations of 131I-IPA (3f-sequential group)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Interval since end of 1st line XRT ≥6 months
• 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.
• 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)
• Male or female ≥18 years of age.
• Karnofsky performance status ≥70. Life expectancy of at least 16 weeks.
• 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 \<120 μmol/L for patients aged 60 years or older
• Urine protein dipstick: no protein
• Female patients surgically sterile or postmenopausal for at least 2 years. Participants of generative potential agreeing to use effective contraception during the period of therapy and 6 months after the end of study.

You may not qualify if:

• Primary XRT dose \< 60 Gy
• 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, alphas/beta=2
• Multifocal distant recurrence, defined as tumour lesion outside the primary XRT field, as evidenced by amino acid-based PET imaging
• Prior treatment with brachytherapy
• Prior treatment with bevacizumab
• Baseline steroid requirement , exceeding physiologic replacement doses ( \<1.5 mg dexamethasone or equivalent per day)
• 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
• 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
• Haemostaseologic conditions, precluding catheterisation or invasive procedures
• Clinically significant illness or clinically relevant trauma within 2 weeks before the administration of the investigational product
• Known impairment of liver or kidney function or known liver or kidney disease, such as hepatitis, cirrhosis, renal failure
• Known human immunodeficiency virus (HIV) positive serology or chronically active hepatitis B or C
• Ongoing toxicity \> grade 2 NCI-CTC (version 4.03) from previous standard or investigational therapies
• Administration of another investigational medicinal product within 90 days prior to screening
• Expected non-compliance with longer-term admission at isolated nuclear medicine ward

Sponsors & Collaborators

• Telix Pharmaceuticals (Innovations) Pty Limited: lead

Study Sites (5)

Lake Macquarie Private Hospital

Gateshead, New South Wales, 2290, Australia

Location

Kepler University Clinic

Linz, 4020, Austria

Location

Medical University of Vienna

Vienna, 1090, Austria

Location

The Netherlands Cancer Institute

Amsterdam, 1066, Netherlands

Location

UMC Utrecht Cancer Center

Utrecht, 3508, Netherlands

Location

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Josef Pichler, MD

  Kepler University Clinic, Linz, Austria

  PRINCIPAL INVESTIGATOR

• Tatjana Traub-Weidinger

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: multi-centre, open-label, dose-finding

Study Record Dates

• First Submitted: January 29, 2019
• First Posted: February 21, 2019
• Study Start: April 9, 2019
• Primary Completion: July 31, 2022
• Study Completion: October 31, 2022
• Last Updated: April 14, 2023

Record last verified: 2021-11

Locations

AU (1); NL (2)