Ignite Creation Date:
2024-05-06 @ 7:07 PM
Last Modification Date:
2024-10-26 @ 3:01 PM
Study NCT ID:
NCT05909618
Status:
RECRUITING
Last Update Posted:
2023-11-28
First Post:
2023-05-01
Brief Title:
Crizanlizumab Alone or in Combination With Nivolumab for Glioblastoma and Melanoma With Brain Metastases
Sponsor:
Sheba Medical Center
Organization:
Sheba Medical Center
Study Overview
Official Title:
An Open Label Phase 2 Study of Intravenously Administered Crizanlizumab Alone or in Combination With Nivolumab for Glioblastoma and Melanoma With Brain Metastases
Status:
RECRUITING
Status Verified Date:
2023-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
14
Brief Summary:
A single-center open-label non-randomized phase III study to evaluate the efficacy safety and tolerance of crizanlizumab monotherapy and in combination with nivolumab in patients with advanced glioblastoma GB who exhausted standard of care SOC therapy patients with metastatic brain melanoma MBM and patients with newly diagnosed unmethylated GB
Subjects will be screened for up to 28 days prior to treatment initiation Eligible subjects will be allocated to one of 3 cohorts
Cohort 1 Patients with metastatic melanoma with primarily diagnosed or newly progressing brain metastases who failed immunotherapy
Cohort 2 Patients with recurrent or progressing GB following primary radiation therapy and temozolomide Patients may have failed up to 2 prior systemic treatment lines including temozolomide as adjuvant therapy and are candidates for further treatment
Cohort 3 Patients with newly diagnosed GB who were evaluated for methylguanine-DNA methyltransferaseMGMT methylation status and have un-methylated MGMT promotor-therefore they are not candidates for maintenance temozolomide therapy
Subjects will be screened for up to 28 days prior to treatment initiation Eligible subjects will be allocated to one of 3 cohorts
Cohort 1 Patients with metastatic melanoma with primarily diagnosed or newly progressing brain metastases who failed immunotherapy
Cohort 2 Patients with recurrent or progressing GB following primary radiation therapy and temozolomide Patients may have failed up to 2 prior systemic treatment lines including temozolomide as adjuvant therapy and are candidates for further treatment
Cohort 3 Patients with newly diagnosed GB who were evaluated for methylguanine-DNA methyltransferaseMGMT methylation status and have un-methylated MGMT promotor-therefore they are not candidates for maintenance temozolomide therapy
Detailed Description:
A single-center open-label non-randomized phase III study to evaluate the efficacy safety and tolerance of crizanlizumab monotherapy and in combination with nivolumab in patients with advanced glioblastoma GB who exhausted standard of care SOC therapy patients with metastatic brain melanoma MBM and patients with newly diagnosed unmethylated GB
Subjects will be screened for up to 28 days prior to treatment initiation Eligible subjects will be allocated to one of 3 cohorts
Cohort 1 Patients with metastatic melanoma with primarily diagnosed or newly progressing brain metastases who failed immunotherapy
Cohort 2 Patients with recurrent or progressing GB following primary radiation therapy and temozolomide Patients may have failed up to 2 prior systemic treatment lines including temozolomide as adjuvant therapy and are candidates for further treatment
Cohort 3 Patients with newly diagnosed GB who were evaluated for MGMT methylation status and have un-methylated MGMT promotor-therefore they are not candidates for maintenance temozolomide therapy
The first 3 subjects enrolled to Cohort 1 and Cohort 2 will receive crizanlizumab 5 mgkg at Cycle 1 Day 1 C1D1 and Cycle 1 Day 15 C1D15 followed by crizanlizumab 5 mgkg every 4 weeks until disease progression evaluated by RECIST 11 and RANO criteria or intolerable toxicity The subsequent 8 patients will receive crizanlizumab 5 miligramkilogram mgkg at C1D1 and C1D15 followed by 5 mgkg every 4 weeks plus nivolumab 3mgkg every 2 weeks until disease progression The subjects will continue the treatment until disease progression or until completion of 27 cycles 2 years Subjects who complete 2 years of therapy will maintain follow-up
Subjects in Cohort 3 will receive crizanlizumab starting from 4 weeks after completing radiation therapy The first 2 subjects will receive crizanlizumab 25 mgkg at C1D1 and C1D15 followed by crizanlizumab 5 mgkg every 4 weeks The subsequent 6 subjects will receive crizanlizumab 5 mgkg at C1D1 and C1D15 followed by crizanlizumab every 4 weeks Treatment will continue for up to 12 months or until disease progression or unacceptable toxicity
Safety and tolerability will be assessed by CTCAE v 60 every week for the first 4 weeks followed by assessments every 2 weeks until Week 12 and then every 4 weeks
Tumor response will be evaluated by brain Magnetic resonance imaging MRI every 8 weeks using RANO criteria Patients with metastatic melanoma will also be evaluated with chest-abdomen and pelvis Computed tomography CT every 8 weeks for the evaluation of visceral disease using RECIST 11
Patients with MBM Cohort 1 whose primary tumornon-brain tumor progresses on RECIST 11 but whose brain tumormetastases show benefit stable disease or better may continue in the study at the investigators discretion
Quality of life will be assessed by the Quality of Life Questionnaire EORTC QLQ-30 and Brain NeoplasmQLQ BN-20 and by cognitive function tests
Archived tissue samples and optional fresh biopsy CSF and blood samples will be drawn to assess pharmacokinetics and pharmacodynamics of the combined therapy and for collateral research aiming to define biomarkers for response
Subjects will be screened for up to 28 days prior to treatment initiation Eligible subjects will be allocated to one of 3 cohorts
Cohort 1 Patients with metastatic melanoma with primarily diagnosed or newly progressing brain metastases who failed immunotherapy
Cohort 2 Patients with recurrent or progressing GB following primary radiation therapy and temozolomide Patients may have failed up to 2 prior systemic treatment lines including temozolomide as adjuvant therapy and are candidates for further treatment
Cohort 3 Patients with newly diagnosed GB who were evaluated for MGMT methylation status and have un-methylated MGMT promotor-therefore they are not candidates for maintenance temozolomide therapy
The first 3 subjects enrolled to Cohort 1 and Cohort 2 will receive crizanlizumab 5 mgkg at Cycle 1 Day 1 C1D1 and Cycle 1 Day 15 C1D15 followed by crizanlizumab 5 mgkg every 4 weeks until disease progression evaluated by RECIST 11 and RANO criteria or intolerable toxicity The subsequent 8 patients will receive crizanlizumab 5 miligramkilogram mgkg at C1D1 and C1D15 followed by 5 mgkg every 4 weeks plus nivolumab 3mgkg every 2 weeks until disease progression The subjects will continue the treatment until disease progression or until completion of 27 cycles 2 years Subjects who complete 2 years of therapy will maintain follow-up
Subjects in Cohort 3 will receive crizanlizumab starting from 4 weeks after completing radiation therapy The first 2 subjects will receive crizanlizumab 25 mgkg at C1D1 and C1D15 followed by crizanlizumab 5 mgkg every 4 weeks The subsequent 6 subjects will receive crizanlizumab 5 mgkg at C1D1 and C1D15 followed by crizanlizumab every 4 weeks Treatment will continue for up to 12 months or until disease progression or unacceptable toxicity
Safety and tolerability will be assessed by CTCAE v 60 every week for the first 4 weeks followed by assessments every 2 weeks until Week 12 and then every 4 weeks
Tumor response will be evaluated by brain Magnetic resonance imaging MRI every 8 weeks using RANO criteria Patients with metastatic melanoma will also be evaluated with chest-abdomen and pelvis Computed tomography CT every 8 weeks for the evaluation of visceral disease using RECIST 11
Patients with MBM Cohort 1 whose primary tumornon-brain tumor progresses on RECIST 11 but whose brain tumormetastases show benefit stable disease or better may continue in the study at the investigators discretion
Quality of life will be assessed by the Quality of Life Questionnaire EORTC QLQ-30 and Brain NeoplasmQLQ BN-20 and by cognitive function tests
Archived tissue samples and optional fresh biopsy CSF and blood samples will be drawn to assess pharmacokinetics and pharmacodynamics of the combined therapy and for collateral research aiming to define biomarkers for response
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None