Proof-of-Concept Study of ACT001 in Adult Patients With Recurrent Glioblastoma Harbouring STAT3-High Signature

Phase 2

Not yet recruiting

• Conditions: Recurrent Glioblastoma
• Interventions: Drug: ACT001

• Registration Number: NCT06894225
• Lead Sponsor: National Neuroscience Institute

Brief Summary

This trial will study the effectiveness of ACT001 in adult patients whose Glioblastoma have recurred with a STAT3-high signature after standard-of-care treatment with at least radiation therapy.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-11-27
• Study First Submitted QC: 2025-03-24
• Study First Posted: 2025-03-25
• Status Verified: 2025-04
• Study Start: 2025-04
• Last Update Submitted: 2025-04-03
• Last Update Posted: 2025-04-06
• Primary Completion: 2026-05
• Study Completion: 2026-05

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

• Histologically confirmed diagnosis of GBM according to 2021 WHO classification
• Availability of tumor tissue representative of GBM from definitive surgery or biopsy and tested to harbour STAT3-High Signature
• Previous treatment with at least radiation therapy
• Documented recurrence of malignant glioma by diagnostic biopsy, resection or MRI performed within 21 days of study enrolment per RANO criteria.

There is no limit on number of previous recurrences or lines of treatment

• At least 12 weeks after the end of prior radiation therapy is required unless there is either: i) histopathologic confirmation of recurrent tumor, or ii) n new enhancement on MRI outside of the radiation treatment field

• An interval of at least 4 weeks after the last administration of any investigational agent or any other treatment prior to first dose of STAT3 inhibitor

• Age 21 years or older on the day of signing informed consent

• Karnofsky performance status (KPS) of 70 or higher

• Patient has adequate bone marrow, renal, and hepatic function ≤ 21 days prior to study enrolment (Step 2) as follows:

  • Absolute neutrophil count (ANC) ≥1,500/mm3
  • Platelets ≥ 100,000/mm3
  • Hemoglobin (Hgb) ≥ 9.0 g/dL (Note: The use of transfusion or other intervention to achieve Hgb ≥ 9.0 g/dL is acceptable.)
  • Renal function: calculated creatinine clearance ≥ 30 mL/min by the Cockcroft-Gault formula
  • Hepatic function: Total bilirubin, Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) ≤ 1.5 times upper limit of normal (ULN). Patients with Gilbert's syndrome documented in medical history may be enrolled if bilirubin is < 3 times ULN.

Exclusion Criteria

• Presence of extracranial metastatic or leptomeningeal disease

• Previous or current treatment with a JAK or STAT3 inhibitor

• Previous or current treatment with bevacizumab/VEGF inhibitor

• Patient is a lactating or pregnant female.

• Symptomatic intra-tumoural haemorrhage

• Severe, active co-morbidity, defined as follows:

  • Patients with clinically defined Acquired Immune-Deficiency Syndrome (AIDS)-defining illness.
  • Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the Investigator may put the patient at high risk of toxicity
  • Any other major medical illnesses or psychiatric impairments that in the Investigator's opinion will prevent administration or completion of protocol therapy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ACT001	ACT001	-

Primary Outcome Measures

Name	Time	Method
Overall Response Rate	1.5 years	ORR as defined as radiographic complete response, or partial response, or stable disease. Patients with stable disease will be considered responders if disease is stable for 24 weeks or more. The regimen will be considered worthy of further study if responses as defined above are observed in at least 3 of the 12 patients.

Secondary Outcome Measures

Name	Time	Method
Progression-free survival (PFS) & Overall survival (OS)	1.5 years	6 months progression-free survival (PFS), defined as proportion of patients who remained alive and progression-free at 6 months.; PFS, which is defined as time from study enrolment to progression of disease per RANO criteria, or death, whichever occurs first. For patients who are not documented to have experienced a PFS event at the time of an analysis, PFS will be right-censored on the date of their last adequate assessment of disease.; Overall survival (OS), which is defined as time from study enrolment to death from any cause. For patients who are not reported to have died at the time of an analysis, OS will be right-censored at the last date the patient is documented to be alive.

Trial Locations

Locations (1)

National Neuroscience Institute; 🇸🇬 Singapore, Singapore