Phase I/II dose escalation trial of radiodynamic therapy (RDT) with 5-Aminolevulinic acid in patients with first recurrence of glioblastoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaet Muenster

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

28 Oct 2022 → ongoing

Decision date (initial)

2024-10-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-517651-12-00

EudraCT number

2021-004631-92

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Dose response

To determine the maximum tolerated dose (MTD*) and safety of (neo)adjuvant RDT; *maxiumun tolerated dose is determined in this study as the maximum tolerated repear RDT consisting og 5-ALA dosing
and radiotherapy

Conditions and MedDRA coding

recurrent glioblastoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Written patient consent after comprehensive information
2. Age >/= 18 years
3. Recurrence of supratentorial glioblastoma after initial resection and adjuvant radio-chemotherapy (with planned second resection cohort 0 and 1), second or third recurrences permitted
4. Clinically indicated further radiotherapy
5. Histological verification of recurrent glioblastoma
6. Karnofsky Performance Score ≥ 60
7. 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 last application of 5-ALA). Such methods include: - 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 - male patients have to use a condom until the end of relevant systemic exposure plus a further 90-day period - sexual abstinence
8. Pre-menopausal female patients with childbearing potential: a negative pregnancy test must be obtained max. 72h prior to treatment start
9. 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.
10. 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

Exclusion criteria 9

1. Patient unable to undergo imaging by MRI, PET or contrast-enhanced CT for whatever reason (e.g. pace-maker)
2. Pregnant and breastfeeding women
3. 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)
4. Any active infection (at the discretion of the investigator)
5. Hypersensitivity against porphyrins
6. Known diagnosis of porphyria
7. Current 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
8. Known intolerance to study medication
9. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. MTD is defined as the most frequent repetitive dose of 5-ALA during 4 weeks of fractionated conformal radiotherapy that does not cause unacceptable side effects, i.e. repeated dose at which no more than 1 of 6 patients suffers a dose-limiting toxicity (DLT). • Toxicological safety of repeat doses of 5-ALA • Neurological safety of RDT • Dermatological safety of RDT • Assess all new AEs CTC AE grade 2 or higher

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaet Muenster

Sponsor organisation

Universitaet Muenster

Address

Schlossplatz 2, Schlossbezirk Schlossbezirk

City

Muenster

Postcode

48149

Country

Germany

Scientific contact point

Organisation

Universitaet Muenster

Contact name

Prof. Dr. med. Walter Stummer

Public contact point

Organisation

Universitaet Muenster

Contact name

Prof. Dr. med. Walter Stummer

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 3 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications