Recurrent Glioblastoma
Conditions
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.
Interventions
DRUGACT001
Patients recruited and have signed informed consent will be initiated on ACT001 400mg twice a day. Treatment course will repeat every 28 days in the absence of disease progression or unacceptable toxicity
Sponsors
National Neuroscience Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Singapore
Contacts
CONTACTDr Lin Xuling
Outcome results
None listed