Radiodynamic Therapy (RDT) With Gliolan in Patients With First Recurrence of Brain Tumor

NCT05590689 | Recruiting Phase 1 DMC

• 2 other identifiers: WWU20_00412021-004631-92
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

The investigational drug 5-ALA (known under the trade name Gliolan®) is an approved drug for the surgical removal of malignant glioma (WHO grade III and IV). In this trial, the drug is being tested outside of its actual approval as a radiosensitizer in combination with conventional radiotherapy for first-time recurrence (relapse) of malignant glioma. In this clinical trial, the investigational drug 5-ALA is being used for the first time in a multiple dose escalation regimen in combination with radiotherapy following surgical removal of a recurrent malignant glioma in humans. The investigational drug, 5-ALA, has been used as a single dose to date as a standard of care for visualization of malignant tissue in the surgical removal of gliomas. The planned clinical trial will first and foremost investigate how well repeated administration of the investigational drug 5-ALA is tolerated in combination with radiotherapy. At the same time, the design of the trial serves to optimize this novel therapeutic procedure with regard to the frequency of administration of the investigational drug 5-ALA in combination with radiotherapy for future clinical trials. As a secondary objective, the efficacy of additional 5-ALA administration will also be investigated.

Conditions

Glioblastoma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)

  In the resent study we will investigate the maximum-tolerated dose (MTD) of the combination of 5-ALA and radiation. MTD is defined as the highest number of RDT that does not cause unacceptable side effects, i.e. at which no more than 1 of 6 patients suffers a dose-limiting toxicity (DLT). DLT describes side effects of a drug that are serious enough to prevent an increase of dose (NCI dictionary of cancer terms). In the present study it is defined as any ≥ Gr.3 hematological toxicity, any ≥ Gr.3 neurological toxicity and any ≥ Gr.3 non-hematological toxicity occurring during the 6 week observation period, that does not resolve to pre-treatment baseline or ≤ Gr. 2 within 3 weeks, either spontaneously or with adequate treatment. To detect any relevant DLT the following aspects are monitored: * Toxicological safety of repeat doses of 5-ALA * Neurological safety of RDT * Dermatological safety of RDT * Assess all new AEs CTCAE grade 2 or higher

  6 weeks after last R(D)T in adjuvant phase

Secondary Outcomes (4)

• Overall survival rate (OSR)

  6 months after first R(D)T in adjuvant phase

• progression-free survival rate (PFS)

  6 months after first R(D)T in adjuvant phase

• event-free survival rate (EFS)

  6 months after inclusion

• concentration changes of immunhistochemistry marker (e.g. Caspase-3, IBA1, H&E, EvG, P53, Ki 67, gammaH2AX)

  during surgery

Other Outcomes (6)

• concentration changes of CPI and CPIII

  6 months after first R(D)T in adjuvant phase

• concentration changes of radiobiological marker CD3

  6 months after first R(D)T in adjuvant phase

• concentration changes of radiobiological marker CD4

  6 months after first R(D)T in adjuvant phase

Study Arms (1)

Radiodynamic therapy (RDT)

EXPERIMENTAL

All patients will be treated with RDT. Patients are devided into cohorts which differs in the total amount and frequence of RDT.

Drug: Gliolan; Radiation: Radiodynamic therapy

Interventions

Gliolan DRUG

A repetitive dose of Gliolan will be administrated in combination with radiotherapy (radiodynamic therapy)

Also known as: 5-Aminolevulinic acid

Radiodynamic therapy (RDT)

Radiodynamic therapy RADIATION

Radiotherapy will be performed in combination with Gliolan administration

Radiodynamic therapy (RDT)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written patient consent after comprehensive information
• Age \>/= 18 years
• Recurrence of supratentorial glioblastoma after initial resection and adjuvant therapy (e.g. radio-chemotherapy, targeted therapies, antiangiogenic therapies as determined by the tumor board) (with planned second resection cohort 0 and 1), second or third recurrences permitted
• Clinically indicated further radiotherapy as per decision of the tumor board as part of therapy for recurrence
• Histological verification of recurrent glioblastoma independent of methylated MGMT promotor status when alkylating chemotherapy failed at this time.
• Karnofsky Performance Score ≥ 60
• For female and male patients and their female partners of childbearing/reproductive potential(\*): Willingness to apply highly effective contraception (Pearl index \<1) during the entire study (and for at least 6 months after the first application of 5-ALA). Such methods include:
• combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: I. oral II. intravaginal III. transdermal
• progestogen only hormonal contraception associated with inhibition of ovulation: I. oral II. injectable III. implantable
• intrauterine device (IUD)
• intrauterine hormone-releasing system (IUS)
• bilateral tubal occlusion
• vasectomised partner
• male patients have to use a condom
• sexual abstinence

You may not qualify if:

• Patient unable to undergo imaging by MRI, PET or contrast-enhanced CT for whatever reason (e.g. pace-maker)
• Pregnant and breastfeeding women
• Past medical history of diseases with poor prognosis, e.g., severe coronary heart disease, heart failure (NYHA III/IV), severe and poorly controlled diabetes, immune deficiency, residual deficits after stroke, severe mental retardation or other serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator)
• Any active infection (at the discretion of the investigator)
• Hypersensitivity against porphyrins
• Known diagnosis of porphyria
• Participation in another clinical trial with therapeutic intervention or use of any other therapeutic interventional agent other than the standard therapy since diagnosis of glioblastoma
• Known intolerance to study medication
• Pre-treatment with other potentially phototoxic or photosensitizing substances (e.g. tetracyclines, sulfonamides, fluoroquinolones, hypericin extracts, products containing St. John's wort ) during the 2 weeks preceding RDT

Sponsors & Collaborators

• Universität Münster: lead
• photonamic GmbH & Co. KG: collaborator

Study Sites (1)

University Hospital Münster, Klinik für Neurochirurgie

Münster, 48149, Germany

RECRUITING

Related Publications (1)

• Pepper NB, Eich HT, Muther M, Oertel M, Rehn S, Spille DC, Stummer W. ALA-RDT in GBM: protocol of the phase I/II dose escalation trial of radiodynamic therapy with 5-Aminolevulinic acid in patients with recurrent glioblastoma. Radiat Oncol. 2024 Jan 22;19(1):11. doi: 10.1186/s13014-024-02408-7.

  PMID: 38254201 DERIVED

MeSH Terms

Conditions

Glioblastoma

Interventions

Aminolevulinic Acid

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

Intervention Hierarchy (Ancestors)

Levulinic Acids; Keto Acids; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Walter Stummer, Prof. Dr.

  University Hospital Muenster

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Walter Stummer, Prof. Dr.

CONTACT

+49 251 8347472; walter.stummer@ukmuenster.de

Hans Theodor Eich, Prof. Dr.

CONTACT

+49 251 8347384; hans.eich@ukmuenster.de

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A modified 3+3 design is used. The maximum tolerated dose of repeated RDT (consisting of 5-ALA dosing an radiotherapy) and safety will be determined in 9 cohorts.

Study Record Dates

• First Submitted: September 7, 2022
• First Posted: October 21, 2022
• Study Start: November 9, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: December 16, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)