Irinotecan-ChemoSeed in Surgically Resectable Glioblastoma (OPTICAL)

Open-label Phase 2 Safety and Efficacy Trial of Irinotecan-ChemoSeed Administered Directly Into the Resection Margin in Patients With Surgically Resectable Glioblastoma

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Glioblastoma
• Intervention / Treatment: Drug: irinotecan-ChemoSeed implementation into the resection cavity after surgical resection of GBM

• Study Type: Interventional
• Enrollment (Estimated): 147
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Chris McConville, Pr; Phone Number: +44 (0) 78342 67819; Email: chrismcconville@extrudedpharmaceuticals.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Dose Determination (Part 1); Dose escalation to identify maximum tolerance dose MTD	Drug: irinotecan-ChemoSeed implementation into the resection cavity after surgical resection of GBM; irinotecan-ChemoSeed implementation into the resection cavity after surgical resection of GBM
Other: Efficacy Testing (Part 2); 2 : 1 randomization irinotecan-ChemoSeed versus standard of care	Drug: irinotecan-ChemoSeed implementation into the resection cavity after surgical resection of GBM; irinotecan-ChemoSeed implementation into the resection cavity after surgical resection of GBM

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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).	39 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	ORR at 6 months by MRI using RANO 2.0 criteria, by independent central review and by investigator assessment.	6 months from recruitment
Disease Control Rate (DCR)	DCR at 12 months by MRI using RANO 2.0 by independent central review and investigator assessment.	12 months from recruitment
Overall Survival	Comparison of Median OS for control and treated arms	39 months

Collaborators and Investigators

• Sponsor: CRISM Therapeutics LTD
• Investigators: Study Chair: Garth S Cruickshank, MBBS, PhD, Emeritus Professor of Neurosurgery, University of Birmingham UK

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: January 13, 2026
• First Submitted That Met QC Criteria: January 13, 2026
• First Posted (Actual): January 21, 2026

Study Record Updates

• Last Update Posted (Actual): January 26, 2026
• Last Update Submitted That Met QC Criteria: January 22, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: ICS1; IRAS ID: 1012556 (Registry Identifier: Regulatory Agency Identifier)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No