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

ConditionGlioblastoma

Trial statusRecruiting

Trial phasePhase 1, Phase 2

Trial typeInterventional

Biological sexAll

Age18-75

SponsorUniversität Münster

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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)

Trial design

Design model

Sequential

Treatments tested in this trial

Gliolan
Drug
A repetitive dose of Gliolan will be administrated in combination with radiotherapy (radiodynamic therapy)
Radiodynamic therapy
Radiation
Radiotherapy will be performed in combination with Gliolan administration

Treatment groups

34 Participants

are divided into 1 treatment group

Group A: Radiodynamic therapy (RDT)Experimental treatment 2 interventions

Trial outcomes

Primary outcomes

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

Time frame

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

Secondary outcomes

Overall survival rate (OSR)

Percentage of patients who are alive 6 months after first R(D)T

Time frame

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

progression-free survival rate (PFS)

Percentage of patients without tumor progression 6 months after first R(D)T in adjuvant phase

Time frame

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

event-free survival rate (EFS)

Percentage of patients without suffering any disease related event such as DLT or progression until 6 months after inclusion

Time frame

6 months after inclusion

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

analytic results of pharma-radio-dynamic tissue changes. Tissue samples collected during surgery of cohort 0 and 1

Time frame

during surgery

Other outcomes

concentration changes of CPI and CPIII

Analytic results for concentration changes as one combined sum parameter

Time frame

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

concentration changes of radiobiological marker CD3

Analytic results for concentration changes

Time frame

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

concentration changes of radiobiological marker CD4

Analytic results for concentration changes

Time frame

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

concentration changes of radiobiological marker CD8

Analytic results for concentration changes

Time frame

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

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Universität Münster

Lead sponsor

photonamic GmbH & Co. KG

Collaborator

Source ClinicalTrials.gov

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