Using Gliolan with Radiotherapy for Recurrent Brain Tumors

Phase I/II Dose Escalation Trial of Radiodynamic Therapy (RDT) With 5-Aminolevulinic Acid in Patients With First Recurrence of Glioblastoma

This study is testing if a new drug called Gliolan can make radiotherapy more effective for patients with recurrent brain tumors after surgery.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 34 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Universität Münster (other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Münster)
• Trial ID: NCT05590689 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the use of the investigational drug 5-ALA (Gliolan) as a radiosensitizer in combination with conventional radiotherapy for patients experiencing their first recurrence of malignant glioblastoma. The study aims to evaluate the safety and tolerability of multiple doses of 5-ALA following surgical removal of the tumor. It represents a novel approach by administering the drug in a multiple dose escalation regimen, which has not been previously tested in this context. The trial will also optimize the treatment protocol to enhance patient outcomes.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with a confirmed recurrence of supratentorial glioblastoma after initial treatment.

Not a fit: Patients with glioblastoma who have not had a recurrence or those with significant comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment efficacy and outcomes for patients with recurrent glioblastoma.

How similar studies have performed: While the use of 5-ALA has been established for visualization during surgery, this specific application as a radiosensitizer in a multiple dose regimen is novel and has not been extensively tested in prior studies.

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

Where this trial is running

Münster

• University Hospital Münster, Klinik für Neurochirurgie — Münster, Germany (RECRUITING)

Study contacts

• Principal investigator: Walter Stummer, Prof. Dr. — University Hospital Muenster
• Study coordinator: Walter Stummer, Prof. Dr.

Conditions: Glioblastoma