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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03849105


Additional trial details provided through ANZCTR are available at the end of this record.


Registration number
NCT03849105
Ethics application status
Date submitted
29/01/2019
Date registered
21/02/2019
Date last updated
14/04/2023

Titles & IDs
Public title
131I-IPA and Concurrent XRT in Recurrent GBM
Scientific title
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
Secondary ID [1] 0 0
131I-IPA-TLX-101-001
Universal Trial Number (UTN)
Trial acronym
IPAX-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Glioblastoma Multiforme 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - 4-L-[131I]iodo-phenylalanine (131I-IPA)

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

Experimental: Three administrations of 131I-IPA (3f-parallel group) - Study participants will be administered in 2GBq in 3 fractions corresponding to ? 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.

Experimental: Three administrations of 131I-IPA (3f-sequential group) - Study participants will be administered in 2GBq in 3 fractions corresponding to ? 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.

Experimental: Dose escalation of fractionated dosing - 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.


Treatment: Other: 4-L-[131I]iodo-phenylalanine (131I-IPA)
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
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety and tolerability parameter Adverse Events
Timepoint [1] 0 0
From first administration of 131I-IPA until 12 months after first administration
Primary outcome [2] 0 0
Safety parameter heart rate
Timepoint [2] 0 0
From first administration of 131I-IPA until 12 months after first administration
Primary outcome [3] 0 0
Safety parameter blood pressure
Timepoint [3] 0 0
From first administration of 131I-IPA until 12 months after first administration
Primary outcome [4] 0 0
Safety parameter Liver function test
Timepoint [4] 0 0
From first administration of 131I-IPA until 12 months after first administration
Primary outcome [5] 0 0
Safety parameter Renal function test
Timepoint [5] 0 0
From first administration of 131I-IPA until 12 months after first administration
Primary outcome [6] 0 0
Safety parameter Full Blood Count
Timepoint [6] 0 0
From first administration of 131I-IPA until 12 months after first administration
Secondary outcome [1] 0 0
To evaluate the maximum tolerated dose (MTD) of 131I -IPA administered concomitantly to 2nd line XRT in recurrent GBM 2
Timepoint [1] 0 0
Evaluation of patient up to 30 days after completion of study therapy
Secondary outcome [2] 0 0
To evaluate the efficacy of a fractionated administration of 131I-IPA
Timepoint [2] 0 0
Up to 6 months after completion of study therapy
Secondary outcome [3] 0 0
Dosimetry
Timepoint [3] 0 0
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
Secondary outcome [4] 0 0
Dosimetry
Timepoint [4] 0 0
Up to 30 days after completion of study therapy
Secondary outcome [5] 0 0
To explore the antineoplastic effect of 131I-IPA + XRT combination therapy
Timepoint [5] 0 0
Commencing just prior to first administration of 131I-IPA until 12 months from time of first therapeutic administration
Secondary outcome [6] 0 0
To explore the occurrence and frequency of pseudo-progression (PP) in response to 131I-IPA + XRT combination therapy
Timepoint [6] 0 0
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
Secondary outcome [7] 0 0
To explore the cognitive function of participants
Timepoint [7] 0 0
Test will be adminsterd at baseline, 45 days post dose of 131I-IPA, Month 3 and Month 6
Secondary outcome [8] 0 0
To explore the cognitive function of participants
Timepoint [8] 0 0
Test will be adminsterd at baseline, 45 days post dose of 131I-IPA, Month 3 and Month 6
Secondary outcome [9] 0 0
To explore the cognitive function of participants
Timepoint [9] 0 0
Test will be adminsterd at baseline, 45 days post dose of 131I-IPA, Month 3 and Month 6

Eligibility
Key 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. Male or female =18 years of age.

6. Karnofsky performance status =70. Life expectancy of at least 16 weeks.

7. 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

8. 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.

9. Written informed consent
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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, alphas/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. Baseline steroid requirement , exceeding physiologic replacement doses ( <1.5 mg
dexamethasone or equivalent per day)

7. 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

8. 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

9. Haemostaseologic conditions, precluding catheterisation or invasive procedures

10. Clinically significant illness or clinically relevant trauma within 2 weeks before the
administration of the investigational product

11. Known impairment of liver or kidney function or known liver or kidney disease, such as
hepatitis, cirrhosis, renal failure

12. Known human immunodeficiency virus (HIV) positive serology or chronically active
hepatitis B or C

13. Ongoing toxicity > grade 2 NCI-CTC (version 4.03) from previous standard or
investigational therapies

14. Administration of another investigational medicinal product within 90 days prior to
screening

15. Expected non-compliance with longer-term admission at isolated nuclear medicine ward

16. In pre-menopausal women: Pregnant as evidenced by a positive pregnancy test, or
breast-feeding

17. Patients with known phenylketonuria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/04/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
31/10/2022
Sample size
Target
Accrual to date
Final
10
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Lake Macquarie Private Hospital - Gateshead
Recruitment postcode(s) [1] 0 0
2290 - Gateshead
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Linz
Country [2] 0 0
Austria
State/province [2] 0 0
Vienna
Country [3] 0 0
Netherlands
State/province [3] 0 0
Amsterdam
Country [4] 0 0
Netherlands
State/province [4] 0 0
Utrecht

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Telix Pharmaceuticals (Innovations) Pty Limited
Address
Country

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/ct2/show/NCT03849105
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Josef Pichler, MD
Address 0 0
Kepler University Clinic, Linz, Austria
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03849105

Additional trial details provided through ANZCTR
Accrual to date
Recruiting in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 10
Lake Macquarie Private Hospital
Recruitment postcode(s) [1] 10
2290
Funding & Sponsors
Funding source category [1] 3
Commercial sector/Industry
Name [1] 3
Telix International Pty Ltd
Address [1] 3
Suite 401 55 Flemington Road
Country [1] 3
Australia
Primary sponsor
Commercial sector/Industry
Primary sponsor name
Telix international Pty Ltd
Primary sponsor address
Suite 401, 55 Flemington Road
North Melbourne, 3051
Primary sponsor country
Australia
Ethics approval
Ethics application status
Approved
Ethics committee name [1] 6
Hunter New England Research Ethics Committee
Address [1] 6
Country [1] 6
Date submitted for ethics approval [1] 6
28/11/2018
Approval date [1] 6
05/06/2019
Ethics approval number [1] 6
2018/ETH00648
 
Public notes

Contacts
Principal investigator
Title 77 0
Dr
Name 77 0
Michael Fay
Address 77 0
Lake Macquarie Private Hospital 36 Pacific Highway Gateshead NSW 2290
Country 77 0
Australia
Phone 77 0
0249184500
Fax 77 0
Email 77 0
[email protected]
Contact person for public queries
Title 78 0
Dr
Name 78 0
Rosalind Wilson
Address 78 0
Suite 401 55 Flemington Road
Country 78 0
Australia
Phone 78 0
+61 3 9093 3808
Fax 78 0
Email 78 0
[email protected]
Contact person for scientific queries
Title 79 0
Dr
Name 79 0
Rosalind Wilson
Address 79 0
Suite 401 55 Flemington Road
Country 79 0
Australia
Phone 79 0
+61 3 9093 3808
Fax 79 0
Email 79 0
[email protected]