PD L 506 for Stereotactic Interstitial Photodynamic Therapy of Newly Diagnosed Supratentorial IDH Wild-type Glioblastoma

Evaluation of the Feasibility of PD L 506 for Stereotactic Interstitial Photodynamic Therapy (iPDT) in Adult Patients With Newly Diagnosed Supratentorial IDH Wild-type Glioblastoma

The trial is an open, multicenter, explorative, pilot phase II study in a small number of patients to assess safety and efficacy of stereotactic interstitial photodynamic therapy (iPDT) with PD L 506 in newly diagnosed supratentorial IDH wild-type glioblastoma.

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma
• Intervention / Treatment: Drug: 5-aminolevulinic acid

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Marcus Stocker, Dr.; Phone Number: +49(0)4101/7853-953; Email: m.stocker@photonamic.de
• Study Contact Backup: Name: Friederike Haubenschild; Email: f.haubenschild@photonamic.de

Study Locations

• Germany
  • Köln, Germany, 50924
    • Not yet recruiting
    • Uniklinik Köln
    • Contact: Maximilian Ruge, Prof. Dr.
  • München, Germany, 81377
    • Recruiting
    • Klinikum der Universität München
    • Contact: Niklas Thon, Prof. Dr.
  • Münster, Germany, 48149
    • Recruiting
    • Universitatsklinikum Munster
    • Contact: Walter Stummer, Prof. Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Biopsy proven, newly diagnosed, supratentorial, unifocal, lobar located IDH wild-type glioblastoma according to the criteria of the 2016 WHO classification.
• Not safely and/or not completely resectable, lobar located, unifocal, supratentorial IDH wild-type glioblastomas with a largest diameter ≤ 40 mm (largest diameter of the contrast enhanced tumor, as defined by enhanced T1 MRI sequences) are eligible in case of corresponding tumor board re-estimations.
• Potentially completely resectable, lobar located, unifocal, supratentorial, IDH wild-type glioblastoma with a largest diameter ≤ 40 mm are eligible in case of both patient's informed preference in favour of iPDT and corresponding tumor board recommendations.
• Age 18 - 70 years
• Karnofsky Performance status (KPS) of ≥ 70 %
• Minimal life expectancy of 3 months.
• Patients eligible for radiotherapy plus concomitant and adjuvant chemotherapy with temozolomide: Adequate haematological function (Absolute neutrophil count (ANC) > 1.5 x 109/L, Platelet count > 100 x 109/L, Haemoglobin > 10 g/dL (may be transfused to maintain or exceed this level)).
• International normalized ratio (INR) or PT (secs) and activated partial thromboplastin time (aPTT) ≤ 1,5 times of the upper limit of normal in the laboratory where it was measured.
• Negative pregnancy test in fertile women
• For female and male patients of reproductive potential: Willingness to apply highly effective contraception (Pearl index <1) during the entire study.

Such methods include :

• combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:

  • oral
  • intravaginal
  • transdermal

• progestogen-only hormonal contraception associated with inhibition of ovulation :

  • oral
  • injectable
  • implantable
• intrauterine device (IUD)
• intrauterine hormone-releasing system (IUS)
• bilateral tubal occlusion
• vasectomised partner
• sexual abstinence • Written informed consent has been signed and dated prior to or at the beginning of Visit -1

Exclusion criteria:

• Glioblastomas involving the basal ganglia, the corpus callosum, the primary motor cortex, the ventricular system, multifocal tumors, and those involving the brain stem and/or the cerebellum.
• Glioblastomas exceeding the 40 mm threshold in their largest diameter
• Simultaneous use of other potentially phototoxic substances (e.g. tetracyclines, sulfonamides, fluoroquinolones, hypericin extracts)
• Hypersensitivity against porphyrins
• Known diagnosis of porphyria
• Acute or chronic hepatic diseases (levels of ASAT, ALAT and/or gamma-GT more than 2.5 times the upper limit of normal in the laboratory where it was measured)
• Manifest renal diseases with renal dysfunction (serum creatinine level > 1.5 times of the upper limit of normal in the laboratory where it was measured)
• Severe, active co-morbidity:
• Unstable angina and/or congestive heart failure within the last 6 months
• Transmural myocardial infarction within the last 6 months
• History of stroke, cerebral vascular accident, or transient ischemic attack within 6 months
• Serious and inadequately controlled cardiac arrhythmia
• Significant vascular disease (e.g. aortic aneurysm)
• Evidence of bleeding diathesis or coagulopathy
• Acute bacterial or fungal infections
• Acute exacerbation of chronic obstructive pulmonary disease
• Hepatic insufficiency resulting in clinical jaundice and/or coagulopathy
• Acquired immune deficiency syndrome; note, however, that HIV testing is not required for study entry.
• Inability to undergo MRI (e.g., presence of a pacemaker)
• Known intolerance to study medication
• Dementia or psychic condition that might interfere with the ability to understand the study and thus give a written informed consent
• Simultaneous participation in another clinical study or participation in another clinical study in the 30 days directly preceding treatment or within 5 plasma half-life of the preceding study drug, whatever is longer.
• Pregnancy or breastfeeding
• In case of both complete absence of intra-operative fluorescence between any of the inserted light diffusers and absence of significant surgery-associated bleedings (i.e. light transmission is detectable between at least two of the inserted light diffusers), the tumor will be classified as 'fluorescence-negative tumor'. iPDT will however be performed. Regarding efficacy evaluation, patients with fluorescence-negative tumors will be excluded from PP-, but included in the ITT-evaluation, and will be evaluated regarding safety.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Interstitial photodynamic therapy; 20 mg 5-aminolevulinic acid per kg body weight orally four hours (range 3,5-4,5 hours) before the induction of general anaesthesia.	Drug: 5-aminolevulinic acid; 5-aminolevulinic acid powder for oral solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the incidence of treatment-emergent Adverse Events (safety and tolerability) of iPDT with PD L 506 in adult patients with newly diagnosed supratentorial IDH wild-type glioblastoma.	The incidence of treatment-emergent Adverse Events (TEAEs) of CTC grades 3, 4 and 5 within two weeks following iPDT	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival rate at 12 months	Percentage of patients without tumor progression 12 months after iPDT	12 months
Overall survival rate at 12 months	Percentage of patients who are alive 12 months after iPDT	12 months
Progression-free survival	Time until first tumor progression	From date of iPDT until the date of first documented progression, up to 66 months
Overall survival	Time until death from any cause	From date of iPDT until the date of death from any cause, up to 66 months
MGMT promoter methylation status of the patient	Analytical results for MGMT promoter methylation status (methylated/unmethylated) in the respective tumor samples of each patient	Baseline
Immune status of the patient	Analytical results for immune parameters (PBMC, CD4+, CD8+) in the respective blood samples of each patient	Baseline, 2 days, 2 weeks after iPDT and then every 3 months, up to 66 months
Results of investigator's assessment of patient's physical condition using Karnofsky performance status scale	To determine patient's physical condition using Karnofsky performance status scale ranging from 0% (worst outcome) to 100% (best outcome)	Baseline, 2 weeks after iPDT and then every 3 months, up to 66 months
Results of investigator's assessment of patient's mental condition using Mini-mental State Examination	To determine patient's mental condition using Mini-mental State Examination scale ranging from 0 (worst outcome) to 30 (best outcome)	Baseline, 2 weeks after iPDT and then every 3 months, up to 66 months
Results of investigator's assessment of patient's mental condition using National Institutes of Health Stroke Scale	To determine patient's mental condition using National Institutes of Health Stroke Scale ranging from 0 (best outcome) to 34 (worst outcome)	Baseline, 2 weeks after iPDT and then every 3 months, up to 66 months
Results of investigator's assessment of patient's condition using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life of Cancer Patients Questionnaire (QLQ-C30) together with the Brain module (BN20)	To determine patient's quality of life	Baseline, 2 weeks after iPDT and then every 3 months, up to 66 months
Interstitial light transmittance and fluorescence data recorded	To determine whether correlations exist between length of OS/PFS and spectral online-monitoring measurement results (transmission and fluorescence measurements)	during iPDT treatment (up to 1 hour)
Interstitial fluorescence data recorded	To determine the rate of patients with fluorescence-negative tumors	during iPDT treatment (up to 1 hour)
Percentage of cylindrical diffusor laser probes without kinks, cracks etc. before and after iPDT for patients treated under protocol versions prior to V7.0	Assessing the safety and performance of the insertion of Cylindrical Diffusor Laser Probes into the brain for iPDT of brain tumors for patients treated under protocol versions prior to V7.0.	Day 0 (Treatment day), directly before and after iPDT
Percentage of guiding catheters without kinks, cracks etc. before and after iPDT	Assessing the safety and performance of the insertion of guiding catheters into the brain for iPDT of brain tumors	Day 0 (Treatment day), directly before and after iPDT
Percentage of iPDT treatments in which the laser system works properly as planned.	Assessing safety and performance of the laser system for iPDT of brain tumors.	Day 0 (Treatment day), directly after iPDT
Percentage of fibers/laser ports which show a maximum deviation in the output power of less than +/-10% to the pre-defined output power of 200 mW/cm diffusor length.	Assessing safety and performance of the combination of ML7710i laser system and Cylindrical Diffusor Laser Probes for the iPDT of brain tumors.	Day 0 (Treatment day), directly after iPDT

Collaborators and Investigators

• Sponsor: photonamic GmbH & Co. KG
• Investigators: Principal Investigator: Niklas Thon, Prof. Dr., Klinikum der Universität München

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2021
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: March 19, 2019
• First Submitted That Met QC Criteria: March 28, 2019
• First Posted (Actual): April 1, 2019

Study Record Updates

• Last Update Posted (Estimated): November 16, 2023
• Last Update Submitted That Met QC Criteria: November 15, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Photosensitizing Agents; Dermatologic Agents; Aminolevulinic Acid
• Other Study ID Numbers: GL 01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No