MedDRA version: 20.0 Level: PT Classification code 10018337 Term: Glioblastoma multiforme System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: FG001
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: Not available
Current Sponsor code: FG001
Other descriptive name: FG001 sodium
Concentration unit
Sponsors
FluoGuide A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients diagnosed with tumor specific contrast enhancement on MRI suggestive of malignant glioblastoma - primary . 2. Scheduled for neurosurgery with the objective to take biopsy, grading or remove cancer tissue 3. Patients aged 18 years or older 4. Capable of understanding and giving written informed consent 5. Women of childbearing potential must agree to use an adequate method of contraception during the trial and for 30 days after the end-of-trial visit. Adequate methods of contraception include intrauterine device or hormonal contraception (oral contraceptive pill, depot injections or implant, transdermal depot patch or vaginal ring). To be considered sterilised or infertile, females must have undergone surgical sterilisation (bilateral tubectomy, hysterectomy or bilateral ovariectomy) or be post-menopausal (defined as at least 12 months amenorrhoea; may be confirmed with follicle-stimulating hormone [FSH] test if there is doubt) 6. Male patients must commit to use barrier contraception (e.g., condom) during the trial and for 30 days after the end-of-trial visit 7. Patient must not previously have received the trial drug (FG001) 8. Patients can only be included if the surgery is planned to be guided by 5-ALA. 9. Patients can only be included if the scheduled surgery is anticipated gross total resection (GTR) with the objective to remove cancer tissue 10. Patients must have normal organ and bone marrow function and be appropriate surgical candidates per site standard of care (SOC). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 34 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1. Any known allergy or hypersensitivity to indocyanine green (ICG) 2. Female patients who are pregnant or breast-feeding (pregnancy test positive prior to inclusion) 3. Overall performance status or co-morbidity deeming the patient unfitted for participation in the trial as judged by the Investigator 4. Pre-existing hepatic and/or renal insufficiency - INR > 1,7 - Estimated GFR (eGFR) <45 ml/min/1,73m2 5. Unwilling or unable to follow the protocol requirements 6. History of allergic reactions attributed to compounds of similar chemical/biologic composition to 5-ALA 7. Known or documented personal or family history of porphyria 8. Prior history of serious gastrointestinal perforation, diverticulitis, and or/peptic ulcer disease 9. Simultaneous participation in another clinical trial receiving a trial drug 10. Simultaneous use of other potentially phototoxic substances (St. John's wort, griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, sulphonamides, quinolones and tetracyclines), and topical preparations containing 5-ALA for 24 hours during the perioperative period.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I: - To evaluate the safety and tolerability of single i.v. doses of FG001 in patients with GBM scheduled for surgery - To establish the optimal dose for imaging of FG001 in patients with GBM Phase II: - To evaluate the efficacy of FG001 in patients with malignant glioma undergoing surgery and to compare it with the efficacy of 5-ALA in patients with malignant glioma undergoing surgery ;Secondary Objective: Phase I: - To determine the pharmacokinetics (PK) profile of single i.v. doses of FG001 - To evaluate the efficacy of FG001 in patients with GBM scheduled for surgery Phase II: - To determine the PK profile of single i.v. doses of FG001 - To evaluate the efficacy of FG001 or 5-ALA after surgery by determination of gross total resection (GTR) - Positive Predicted Value (PPV) of FG001 and 5-ALA fluorescence tumor tissue obtained from each trial patient - To evaluate the contrast of FG001 for the surgeon to differentiate tumor tissue from normal tissue - Evaluate the NPV from each trial patient of FG001 and compare with 5-ALA - To evaluate the safety and tolerability of the optimal i.v. dose of FG001 in patients with malignant glioma scheduled for surgery ;Primary end point(s): Phase I: a. Safety and tolerability evaluated by: - Adverse events (AEs) - Laboratory parameters (Clinical chemistry) - 12-lead ECG parameters - Vital signs (including systolic and diastolic blood pressure, pulse, body temperature and respiratory rate) b. Establish optimal dose - Dose of FG001 giving the highest intra-operative tumor-to-background ratio (TBR) Phase II: - The proportion of patients with at least one indeterminated tissue or unexpected fluorescent tissue at the End of Surgery (EOS), where FG001- or 5-ALA-induced fluorescence is consistent with the histology;Timepoint(s) of evaluation of this end point: Data Collection timepoints are from 1 hour and up to 48 Hours from administration of FG001 (post-injection FG001) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase I: a. Evaluation of sensitivity and specificity of FG001 b. PK profile determined by non-compartmental analysis: - Peak plasma concentration (C max) - Area under the plasma concentration-time curve from time-zero extrapolated to infinity (AUC 0-inf) - Area under the plasma concentration-time curve from time-zero to last quantifiable concentration (AUC 0-t) - Terminal half-life (t ½) Phase II: a. PK profile determined by non-compartmental analysis: - Peak plasma concentration (Cmax) - Area under the plasma concentration-time curve from time-zero extrapolated to infinity (AUC0-inf) - Area under the plasma concentration-time curve from time-zero to last quantifiable concentration (AUC0-t) - Terminal half-life (t½) b. Determination of the percentage of patients with gross total resection by post-MRI scans guided by either FG001 or 5-ALA c. Positive Predicted Value (PPV) of FG001 and 5-ALA fluorescence of the single bulk tumor tissue obtained from each trial patient d. Negative Predictive Value (NPV) of FG001 and 5-ALA of biopsies obtained nearby fluoresence tumor areas from each trial patient e. Safety and tolerability evaluated by: - Adverse events - Laboratory parameters - 12-lead ECG parameters - Vital signs (including systolic and diastolic blood pressure, pulse, body temperature and respiratory rate) f. Evaluation of TBR values for FG001 ;Timepoint(s) of evaluation of this end point: Data Collection timepoints are from 1 hour and up to 48 Hours from administration of FG001 (post-injection FG001) | — |
Countries
Denmark, Sweden
Contacts
Public ContactAnn Christine Korsgaard
Ozack ApS
Outcome results
None listed