Glioblastoma
Conditions
Brief summary
Part 1 (dose escalation, safety, and preliminary efficacy) Part 1 is a non-randomised, single-arm design in 12 participants with recurrent GBM suitable for maximal safe surgical resection. Part 1 will evaluate safety, determine the MTD of irinotecan-ChemoSeed and the RP2D (corresponding to coverage of as much of the resection cavity as possible, up to the MTD) and evaluate efficacy. All Part 1 participants will be administered irinotecan- ChemoSeed concurrent to Standard of Care (SoC) treatment. Part 1 dose- escalation will start at 72 mg of IRN Part 2, in 135 participants with newly diagnosed GBM suitable for maximal safe surgical resection, will assess the efficacy of irinotecan-ChemoSeed. The actual number of irinotecan-ChemoSeeds administered into the resected tumour margin of the tumour cavity after surgical resection will be at the discretion of the neurosurgical consultant up to the MTD, to cover as much of the resection cavity as possible. Participants will be randomised in a 2:1 ratio: * Arm 1: Irinotecan-ChemoSeed +SoC: Irinotecan-Chemoseeds administered into the resection margin following maximal safe surgical resection, with fractionated RT, concomitant and maintenance TMZ (based on Stupp protocol) starting 4 to 6 weeks after surgery per institution standard practice. * Arm 2: SoC treatment only: maximal safe surgical resection with fractionated RT, concomitant and maintenance TMZ (based on Stupp protocol) starting 4 to 6 weeks after surgery per institution standard practice.
Interventions
DRUGirinotecan-ChemoSeed implementation into the resection cavity after surgical resection of GBM
irinotecan-ChemoSeed implementation into the resection cavity after surgical resection of GBM
Sponsors
CRISM Therapeutics LTD
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 1\. Radiologically relapsed, neuropathologically verified GBM (by the WHO 2021 criteria) (Part 1) or newly diagnosed, radiologically suspected GBM (Part 2) amenable to surgical resection. 2\. Male or female aged 18 years or older. 3. Ability to understand and the willingness to sign a written informed consent form (ICF). 4\. KPS ≥ 70. 5. Life expectancy ≥ 6 months. 6. Adequate organ and marrow function as follows (all required): 1. Absolute neutrophil count ≥ 1.5 k/µL 2. Platelets ≥ 100 k/µL 3. Haemoglobin ≥ 9 g/dL 4. Serum creatinine ≤ 1.8 mg/dL or creatinine clearance \> 50 mL/min 5. Bilirubin ≤ 1.5 mg/dL 6. Alanine aminotransferase (ALT) ≤ 3.0 × upper limit of normal (ULN) 7. Aspartate aminotransferase (AST) ≤ 3.0 × ULN 8. Prothrombin time ≤ 1.5 × ULN 9. International normalised ratio (INR) ≤ 1.5 × ULN 10. Partial thromboplastin time ≤ 1.5 × ULN 7. Women of childbearing potential must agree to use a highly effective method of contraception for the duration of the trial or for 5X the systemic half-life (i.e., 6 weeks) plus 6 months following irinotecan-ChemoSeed administration, whichever is the longest.. Female participants must refrain from egg donation during the same time period. 8. Male participants of reproductive potential, who intend to be sexually active with a female partner of childbearing potential, must commit to use barrier contraception (e.g., condom) for the duration of the trial or for 5X the systemic half-life (i.e., 6 weeks) plus 6 months following irinotecan-ChemoSeed administration, whichever is the longest. Male participants must not donate or bank sperm during the same time period.
Exclusion criteria
* 1\. Multicentric disease defined by tumours which have multiple discrete areas of contrast enhancing or non-enhancing tumour without connecting T2/ fluid-attenuated inversion recovery (FLAIR) signal abnormality. 2. Diffuse leptomeningeal disease. 3. Not eligible for surgical resection. 4. Known hypersensitivity to IRN or PLGA. 5. Prior IRN treatment (for Part 2 participants) less than 12 months from trial enrolment 6. Pregnant or lactating women or participants who intend to get pregnant during the trial. 7\. Prior active malignancy except for non-melanoma skin cancer and carcinoma in situ (of the cervix or bladder), unless diagnosed and definitively treated more than 3 years prior to surgical resection and trial drug administration. 8. Part 1 participants with relapsed GBM: treatment with another investigational drug or other intervention within 4 weeks prior to the surgical resection or 5 times the half-life (whichever is longer) before trial drug administration. 9. Part 2 participants with newly diagnosed GBM: prior RT, chemotherapy, immunotherapy, or targeted agents administered specifically for the lesion being treated.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 To determine the optimal Dose of Irinotecan (RP2D) to be administered for Part 2. | 13 months | — |
| Part 2. Determination Of Progression Free Survival (PFS) to demonstrate the superiority of irinotecan-ChemoSeed compared to concurrent to SoC treatment | 39 months | To demonstrate superiority of irinotecan-ChemoSeed concurrent to SoC treatment and administered into the resection margin following maximal safe surgical resection relative to SoC treatment alone, by assessment of progression-free survival (PFS). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | 6 months from recruitment | ORR at 6 months by MRI using RANO 2.0 criteria, by independent central review and by investigator assessment. |
| Disease Control Rate (DCR) | 12 months from recruitment | DCR at 12 months by MRI using RANO 2.0 by independent central review and investigator assessment. |
| Overall Survival | 39 months | Comparison of Median OS for control and treated arms |
Countries
United Kingdom
Contacts
CONTACTChris McConville, Pr
STUDY_CHAIRGarth S Cruickshank, MBBS, PhD
Emeritus Professor of Neurosurgery, University of Birmingham UK
Outcome results
None listed