A Multicenter, Randomized, Open-label, Controlled Phase II Clinical Trial to Evaluate the Efficacy and Safety of CAN008 Combined With Re-irradiation (rRT) for Treating Patients With Recurrent Glioblastoma (GBM)
Overview
- Phase
- Phase 2
- Intervention
- CAN008
- Conditions
- GBM
- Sponsor
- CANbridge Life Sciences Ltd.
- Enrollment
- 60
- Primary Endpoint
- Overall survival
- Last Updated
- 7 years ago
Overview
Brief Summary
This is a multicenter, randomized, controlled study, aiming to evaluate the efficacy and safety of CAN008 administered once-weekly with rRT for treating first tumor recurrence in patients with GBM.
Detailed Description
This is a multi-center, randomized, controlled clinical trial to evaluate the efficacy and safety of CAN008 administered once-weekly with re-radiation therapy (rRT) in patients with an initial relapse of GBM. The subjects will be randomized into the treatment group (CAN008 + rRT) or the control group (rRT). The investigational treatment can be continued as long as the subjects have experienced lasting clinical benefits (complete response \[CR\], partial response \[PR\] or stable disease \[SD\]). This study will be carried out in GBM subjects with an initial or second relapse. The subjects must have received standard care, including combination of radiotherapy and TMZ after surgical resection, and must be candidates for re-radiation therapy (rRT).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects with histologically diagnosed GBM confirmed by pathological tests at the central laboratory;
- •Subjects who have definite CD95L IHC expression level and CD95L methylation level results confirmed at the central laboratory;
- •Subjects with GBM who are not suitable for surgical ablation after tumor recurrence or have residual neoplasm after surgical ablation;
- •Patients with disease progression or recurrence based on RANO (Response Assessment in Neuro-oncology) Criteria identified upon magnetic resonance imaging (MRI) performed two weeks prior to the first dose of investigational drug and two weeks prior to the initiation of rRT;
- •Age ≥ 18 years and ≤ 70 years;
- •Expected survival ≥ 3 months;
- •Karnofsky score ≥60;
- •Subjects who have tumor progression after having previously received standard treatments including surgery, chemoradiation combination (RT+ TMZ), adjuvant chemotherapy (TMZ);
- •Subjects who have a single primary lesion or have scattered or multiple lesions which can be contained within a radiation target volume;
- •Subjects who have received a maximum dose of 60 Gy for a single tumor in situ in the previous RT, or have not received RT for at least 8 months;
Exclusion Criteria
- •Subjects who have previously received more than one course of RT for the head or have received a total dose of \>60 Gy in the previous RT;
- •Subjects who have received an accumulated radiation dose of \>54 Gy for the optic chiasma;
- •Subjects whose scattered or multiple tumors cannot be included within a radiation target volume;
- •Subjects who have previously received treatment with bevacizumab, iodine radiotherapy, gamma knife and/or brachytherapy;
- •Subjects who cannot undergo MRI examination or follow-ups;
- •Subjects with human immunodeficiency virus (HIV) infection;
- •Subjects with active viral hepatitis need to be excluded:
- •For those with inactive viral hepatitis, they can be considered to be enrolled in this trial if their liver function is within the allowable range, that is, hepatitis B virus deoxyribonucleic acid (HBV- DNA)\<2,000 IU/Ml;
- •For those infected with hepatitis C virus (HCV), they can also be considered to be included if no HCV ribonucleic acid (HCV-RNA) is detected;
- •Subjects who have hereditary fructose intolerance (HFI);
Arms & Interventions
Treatment Group
CAN008 400 mg weekly over no less than 30 minutes via intravenous drip, followed by rRT that same day
Intervention: CAN008
Control Group
The dose is 2.0 Gy/d, 5 times/week, with a total planned radiation dose of 36 Gy.
Intervention: CAN008
Outcomes
Primary Outcomes
Overall survival
Time Frame: From date of randomization until the date of death from any cause,assessed up to 12 months
Secondary Outcomes
- Objective response rate (ORR)(rom date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 8 months").)
- Duration of response (DOR)(rom date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 8 months").)
- Progression free survival (PFS)("From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months)
- 6-month progression free survival rate (PFS6)(The percentage of subjects confirmed without PD or death at 6 months after randomization.)