Trial document




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  DRKS00020543

Trial Description

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Title

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

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Trial Acronym

GL 01

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URL of the Trial

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Brief Summary in Lay Language

The introduction of radiation therapy combined with chemotherapy has significantly improved life expectancy for patients with a malignant brain tumor. The expected survival after combined radiation / chemotherapy is currently around 15 months. Despite these advances, life expectancy for these patients remains very poor. New treatment options are therefore absolutely necessary.

One of these new, potentially promising treatment options is photodynamic therapy. In so-called stereotactic interstitial photodynamic therapy, thin optical fibers are placed in the tumor in a minimally invasive and millimeter-precise manner at predetermined target points in such a way that the tumor volume can be irradiated as completely as possible.
In recently published case reports, it was surprisingly common to observe disease-free survival of more than 30 months in patients with a malignant brain tumor after using this new form of therapy.

PD L 506 has been approved under the brand name Gliolan® since 2007 for the visualization of tumor tissue in malignant gliomas (WHO grades III and IV). Although PD L 506 is used for the first time in this study for stereotactic interstitial photodynamic therapy in patients with a malignant brain tumor, extensive knowledge of the safety and tolerability of PD L506 is available, which help to assess the tolerability profile of the study drug for iPDT.

Taking into account the possible benefits of this new treatment method for patients with malignant brain tumor, it is considered justified to investigate the potential usefulness of PD L 506 in this patient group in the context of this study.

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Brief Summary in Scientific Language

The introduction of radiotherapy with concurrent and adjuvant temozolomide chemotherapy has significantly improved the prognosis for glioblastoma patients. The expected median survival after chemoradiation is currently around 15 months. Despite these advances, the prognosis for glioblastoma patients remains very poor. New therapeutic approaches are therefore absolutely necessary.

One of these new, potentially promising therapeutic methods is photodynamic therapy (PDT). In stereotactic interstitial photodynamic therapy (iPDT), thin optical fibers are implanted minimally invasively and with millimeter precision at previously defined target points so that the tumor volume can be irradiated as completely as possible.
In recent case reports, after using iPDT, progression-free survival of more than 30 months was surprisingly common in glioblastoma patients.

PD L 506 has been approved under the brand name Gliolan® since 2007 for the visualization of tumor tissue in malignant gliomas (WHO grades III and IV). Although PD L 506 is being used for the first time in the context of this prospective study for iPDT in patients with glioblastomas, extensive knowledge of the safety and tolerability of PD L506 is available, which contribute to the assessment of the tolerability profile of the study drug for iPDT.

Taking into account the potential benefits of iPDT in the treatment of glioblastomas, it is considered warranted to investigate the potential usefulness of PD L 506 in this patient group in this study.

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Do you plan to share individual participant data with other researchers?

No

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Description IPD sharing plan:

The development concept does not provide for the sharing of anonymized patient data.

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Organizational Data

  •   DRKS00020543
  •   2020/01/29
  •   2019/04/01
  •   no
  •   Approved
  •   18-708 fed, Ethik-Kommission der Medizinischen Fakultät der Ludwig-Maximilians-Universität München
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Secondary IDs

  •   2016-004775-51 
  •   NCT03897491  (ClinicalTrials.gov)
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Health Condition or Problem studied

  •   C71 -  Malignant neoplasm of brain
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Interventions/Observational Groups

  •   PD L 506 (Active ingredient: 5-Aminolevulinic acid /5-ALA) will be orally administered to the patient in a dosage of 20 mg/kg BW. Interstitial photodynamic therapy of the glioblastoma will be started (with a light power of 200 mW/cm diffuser length) approx. six
    hours after administration of PD L 506 using a diode laser emitting light at a wavelength of 635 nm and optical fibers with cylindrical light diffuser region.
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Characteristics

  •   Interventional
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  •   Single arm study
  •   Open (masking not used)
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  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   II
  •   Yes
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Primary Outcome

To determine safety and tolerability of iPDT with PD L 506 in adult patients with newly diagnosed supratentorial IDH wild-type glioblastoma.
Primary parameter: The incidence of treatment-emergent Adverse Events (TEAEs) of CTC grades III, IV and V within two weeks following iPDT.

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Secondary Outcome

• To determine the progression-free survival (PFS) rate and the overall survival (OS) rate 12 months after iPDT
• To determine length of PFS and OS
• To determine whether MGMT promoter methylation gains prognostic/predictive impact after iPDT
• To determine whether correlations exist between length of OS/PFS and spectral online-monitoring measurement results (transmission and fluorescence measurements)
• To determine the rate of patients with fluorescence-negative tumors
• To determine patient’s mental and physical condition using Karnofsky performance status scale (KPSS), Mini–mental State Examination (MMSE), National Institutes of Health Stroke Scale (NIHSS), EORTC QLQ-C30 and module QLQ-BM20) 14 days after iPDT and then at every follow-up visit.

Additional Exploratory Study Objective:
• To determine whether there is an influence of iPDT on immune parameters (PBMC, CD4+, CD8+)

Additional Exploratory Study Objectives for Medical Devices:
• Assessing the safety and performance of the insertion of Cylindrical Diffusor Laser Probes into the brain for iPDT of brain tumors.
• Assessing safety and performance of the ML7710i laser system for iPDT of brain tumors.
• Assessing safety and performance of the combination of ML7710i laser system and Cylindrical Diffusor Laser Probes for the iPDT of brain tumors.

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
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Recruitment

  •   Planned
  •   2021/02/18
  •   20
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   70   Years
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Additional 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 include3:
- combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
o oral
o intravaginal
o transdermal
- progestogen-only hormonal contraception associated with inhibition of ovulation :
o oral
o injectable
o implantable
- intrauterine device (IUD)
- intrauterine hormone-releasing system (IUS)
- bilateral tubal occlusion
- vasectomised partner
- sexual abstinence
• Written informed consent has been signed prior to or at Visit 1

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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.

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Addresses

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    • photonamic GmbH & Co. KG
    • Eggerstedter Weg 12
    • 25421  Pinneberg
    • Germany
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    • photonamic GmbH & Co. KG
    • Mr.  Dr.  Marcus  Stocker 
    • Eggerstedter Weg 12
    • 25421  Pinneberg
    • Germany
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    • photonamic GmbH & Co. KG
    • Mr.  Dr.  Marcus  Stocker 
    • Eggerstedter Weg 12
    • 25421  Pinneberg
    • Germany
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Sources of Monetary or Material Support

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    • photonamic GmbH & Co. KG
    • Eggerstedter Weg 12
    • 25421  Pinneberg
    • Germany
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Status

  •   Recruiting planned
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Trial Publications, Results and other Documents

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