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

Studien-Informationen Einschlusskriterien Studien-Rationale Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT05590689

Studienbeginn:
November 2022

Letztes Update:
05.01.2024

Wirkstoff:
Gliolan

Indikation (Clinical Trials):
Glioblastoma, Recurrence

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Universität Münster

Collaborator:
photonamic GmbH & Co. KG

Studienleiter

Walter Stummer, Prof. Dr.
Principal Investigator
University Hospital Muenster

Kontakt

Walter Stummer, Prof. Dr.
Kontakt:
Phone: +49 251 8347472
E-Mail: walter.stummer@ukmuenster.de» Kontaktdaten anzeigen

Hans Theodor Eich, Prof. Dr.
Kontakt:
Phone: +49 251 8347384
E-Mail: hans.eich@ukmuenster.de» Kontaktdaten anzeigen

Studienlocations
(1 von 1)

University Hospital Münster, Klinik für Neurochirurgie
48149 Münster
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Walter Stummer, Prof. Dr.» Ansprechpartner anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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

Studien-Rationale

Primary outcome:

1. Maximum tolerated dose (MTD) (Time Frame - 6 weeks after last R(D)T in adjuvant phase):
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

Secondary outcome:

1. Overall survival rate (OSR) (Time Frame - 6 months after first R(D)T in adjuvant phase):
Percentage of patients who are alive 6 months after first R(D)T

2. progression-free survival rate (PFS) (Time Frame - 6 months after first R(D)T in adjuvant phase):
Percentage of patients without tumor progression 6 months after first R(D)T in adjuvant phase

3. event-free survival rate (EFS) (Time Frame - 6 months after inclusion):
Percentage of patients without suffering any disease related event such as DLT or progression until 6 months after inclusion

4. concentration changes of immunhistochemistry marker (e.g. Caspase-3, IBA1, H&E, EvG, P53, Ki 67, gammaH2AX) (Time Frame - during surgery):
analytic results of pharma-radio-dynamic tissue changes. Tissue samples collected during surgery of cohort 0 and 1

Geprüfte Regime

Gliolan (5-Aminolevulinic acid):
A repetitive dose of Gliolan will be administrated in combination with radiotherapy (radiodynamic therapy)
Radiodynamic therapy:
Radiotherapy will be performed in combination with Gliolan administration

Quelle: ClinicalTrials.gov

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