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131I-IPA + XRT as Treatment for Patients With Glioblastoma Multiforme (IPAX-1)

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ClinicalTrials.gov Identifier: NCT03849105
Recruitment Status : Recruiting
First Posted : February 21, 2019
Last Update Posted : August 20, 2019
Sponsor:
Information provided by (Responsible Party):
Telix International Pty Ltd

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

Condition or disease Intervention/treatment Phase
Glioblastoma Multiforme Radiation: 4-L-[131I]iodo-phenylalanine (131I-IPA) Phase 1 Phase 2

Detailed Description:

Primary objective To assess the safety and tolerability of intravenous 131I-IPA administered concomitantly to 2nd line XRT in recurrent GBM

Secondary objectives

  1. To assess the maximum tolerated dose (MTD) of 131I -IPA administered concomitantly to 2nd line XRT in recurrent GBM
  2. To evaluate the feasibility of a fractionated administration of 131I-IPA
  3. To evaluate the radiation absorbed dose to tumour from 131I-IPA
  4. To confirm biodistribution and absorbed doses to whole body and organs from 131I-IPA
  5. To explore the antineoplastic effect of 131I-IPA + XRT combination therapy
  6. To explore the occurrence and frequency of pseudo-progression (PP) in response to 131I-IPA + XRT combination therapy
  7. To explore the cognitive function before, during and after therapy

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: multi-centre, open-label, dose-finding
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multi-centre, Open-label, Single-arm, Dose-finding Phase I/II Study to Evaluate Safety, Tolerability, Dosing Schedule, and Preliminary Efficacy of 131I-IPA, Administered in Patients With Recurrent GBM, Concomitantly With 2nd Line XRT
Actual Study Start Date : April 9, 2019
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2021


Arm Intervention/treatment
Experimental: Single administration of 131I-IPA
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)

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

Other Name: external radiotherapy

Experimental: three administrations of 131I-IPA
Study participants with GBM receive three administrations of 4-L-[131I]iodo-phenylalanine (131I-IPA) at weekly intervals. Commencing between the first two administrations of 131I-IPA the patient will also commence external radiotherapy, receiving 18 cycles, with each cycle being of 2 Gy.
Radiation: 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

Other Name: external radiotherapy




Primary Outcome Measures :
  1. Safety and tolerability parameter Adverse Events [ Time Frame: From first administration of 131I-IPA until 12 months after first administration ]
    Treatment-related adverse events according to NCI-CTCAE v 4.03 criteria will be captured and evaluated for each patient

  2. Safety parameter heart rate [ Time Frame: From first administration of 131I-IPA until 12 months after first administration ]
    Frequency of occurrence and severity of abnormal findings as measured by beats per minute

  3. Safety parameter blood pressure [ Time Frame: From first administration of 131I-IPA until 12 months after first administration ]
    Frequency of occurrence and severity of abnormal findings as measured by mmHg

  4. Safety parameter Liver function test [ Time Frame: From first administration of 131I-IPA until 12 months after first administration ]
    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.

  5. Safety parameter Renal function test [ Time Frame: From first administration of 131I-IPA until 12 months after first administration ]
    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.

  6. Safety parameter Full Blood Count [ Time Frame: From first administration of 131I-IPA until 12 months after first administration ]
    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.


Secondary Outcome Measures :
  1. To evaluate the maximum tolerated dose (MTD) of 131I -IPA administered concomitantly to 2nd line XRT in recurrent GBM 2 [ Time Frame: Evaluation of patient up to 30 days after completion of study therapy ]
    MTD will be calculated in cohorts of 3 patients that are evaluated for treatment-related adverse events according to NCI-CTCAE v 4.03. Dose will be escalated until such time that treatment-related grade 3 adverse events occur.

  2. To evaluate the efficacy of a fractionated administration of 131I-IPA [ Time Frame: Up to 6 months after completion of study therapy ]
    This outcome will be evaluated by comparing morphological outcomes to treatment, as assessed by imaging, between two treatment groups. The first treatment group having the dose administered in a single administration, whilst the second group will have the dose administered in three administrations

  3. Dosimetry [ Time Frame: 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 ]
    To evaluate the radiation absorbed dose to tumour from 131I-IPA

  4. Dosimetry [ Time Frame: Up to 30 days after completion of study therapy ]
    To confirm biodistribution and absorbed doses to whole body and organs from 131I-IPA

  5. To explore the antineoplastic effect of 131I-IPA + XRT combination therapy [ Time Frame: Commencing just prior to first administration of 131I-IPA until 12 months from time of first therapeutic administration ]
    This outcome will be determined in all patients by the use of sequential CT imaging in order to determine response of the lesion to the therapy according to RANO criteria.

  6. To explore the occurrence and frequency of pseudo-progression (PP) in response to 131I-IPA + XRT combination therapy [ Time Frame: 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 ]
    This outcome will be determined in all patients by the use of sequential CT imaging in order to determine the presence of pseudo progression as defined by the RANO criteria response to 131I-IPA + XRT combination therapy

  7. To explore the cognitive function of participants [ Time Frame: Test will be adminsterd at baseline, 45 days post dose of 131I-IPA, Month 3 and Month 6 ]
    This outcome will be determined in all patients through the use of the Trail Making Test

  8. To explore the cognitive function of participants [ Time Frame: Test will be adminsterd at baseline, 45 days post dose of 131I-IPA, Month 3 and Month 6 ]
    This outcome will be determined in all patients through the use of the HVLT-R

  9. To explore the cognitive function of participants [ Time Frame: Test will be adminsterd at baseline, 45 days post dose of 131I-IPA, Month 3 and Month 6 ]
    This outcome will be determined in all patients through the use of the MAE COWA test



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03849105


Contacts
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Contact: Telix Pharmaceuticals +61 3 9093 3808 global-clinicaltrials@telixpharma.com

Locations
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Australia, New South Wales
Lake Macquarie Private Hospital Recruiting
Gateshead, New South Wales, Australia, 2290
Contact: Michael Fay, MD         
Austria
Kepler University Clinic Recruiting
Linz, Austria, 4020
Contact: Josef Pichler, MD    +435768087    josef.pichler@kepleruniklinikum.at   
Principal Investigator: Josef Pichler, MD         
Medical University of Vienna Recruiting
Vienna, Austria, 1090
Contact: Tatjana Traub-Weidinger, MD         
Netherlands
The Netherlands Cancer Institute Recruiting
Amsterdam, Netherlands, 1066
Contact: Wouter Vogel, MD         
UMC Utrecht Cancer Center Recruiting
Utrecht, Netherlands, 3508
Contact: Arthur J.A.T. Braat, MD         
Sponsors and Collaborators
Telix International Pty Ltd
Investigators
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Principal Investigator: Josef Pichler, MD Kepler University Clinic, Linz, Austria
Principal Investigator: Tatjana Traub-Weidinger Medical University of Vienna

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Responsible Party: Telix International Pty Ltd
ClinicalTrials.gov Identifier: NCT03849105     History of Changes
Other Study ID Numbers: 131I-IPA-TLX-101-001
First Posted: February 21, 2019    Key Record Dates
Last Update Posted: August 20, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Telix International Pty Ltd:
glioblastoma multiforme (GBM),
External Radiotherapy
131I-IPA
Additional relevant MeSH terms:
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Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue