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

NCT ID: NCT05590689

Last Updated: 2024-12-16

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-09
• Study Completion Date: 2027-01-31

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

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Radiodynamic therapy (RDT)

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

Group Type: EXPERIMENTAL

Gliolan

Intervention Type: DRUG

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

Radiodynamic therapy

Intervention Type: RADIATION

Radiotherapy will be performed in combination with Gliolan administration

Interventions

Gliolan

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

Intervention Type: DRUG

Radiodynamic therapy

Radiotherapy will be performed in combination with Gliolan administration

Intervention Type: RADIATION

Other Intervention Names

5-Aminolevulinic acid

Eligibility Criteria

Inclusion Criteria

• 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:

1. combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: I. oral II. intravaginal III. transdermal

2. progestogen only hormonal contraception associated with inhibition of ovulation: I. oral II. injectable III. implantable

3. intrauterine device (IUD)

4. intrauterine hormone-releasing system (IUS)

5. bilateral tubal occlusion

6. vasectomised partner

7. male patients have to use a condom

8. sexual abstinence

• Pre-menopausal(*) female patients with childbearing potential: a negative pregnancy test must be obtained max. 72h prior to treatment start
• Adequate liver function: bilirubin < 1.5 times above upper limit of normal range (ULN), alanine transaminase (ALT/SGPT) and aspartate transaminase (AST/SGOT) < 3 times ULN. In the case of documented or suspected Gilbert's disease bilirubin < 3 times ULN.
• Adequate renal function: creatinine < 3 times above ULN; eGFR >/= 60 ml/min, Blood clotting: INR/Quick/PT and PTT within acceptable limits according to the investigator.

(*) Definition: A man is considered of reproductive potential after puberty unless permanently sterile by bilateral orchidectomy. A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A post-menopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

photonamic GmbH & Co. KG

INDUSTRY

Sponsor Role: collaborator

Universität Münster

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Walter Stummer, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

University Hospital Muenster

Locations

University Hospital Münster, Klinik für Neurochirurgie

Münster, , Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Walter Stummer, Prof. Dr.

Role: CONTACT

Phone: +49 251 8347472

Email: walter.stummer@ukmuenster.de

Hans Theodor Eich, Prof. Dr.

Role: CONTACT

Phone: +49 251 8347384

Email: hans.eich@ukmuenster.de

Facility Contacts

Walter Stummer, Prof. Dr.

Role: primary

References

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.

Reference Type: DERIVED

PMID: 38254201 (View on PubMed)

Other Identifiers

2021-004631-92

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

WWU20_0041

Identifier Type: -

Identifier Source: org_study_id