NCT05909618RecruitingPhase 2
Crizanlizumab Alone or in Combination With Nivolumab for Glioblastoma and Melanoma With Brain Metastases
An Open Label Phase 2 Study of Intravenously Administered Crizanlizumab Alone or in Combination With Nivolumab for Glioblastoma and Melanoma With Brain Metastases
Source: ClinicalTrials.gov · Last updated 22 Jul 2025 · Not updated for over 12 months - ask the site whether it is still open
Brief summary (registry, in English)
A single-center, open-label, non-randomized phase I/II 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 methyltransferase(MGMT) methylation status and have un-methylated MGMT promotor-therefore, they are not candidates for maintenance temozolomide therapy.
- Status (registry)
- Recruiting
- Phase (registry)
- Phase 2
- Study type
- Interventional
- Enrollment
- 33 (estimated)
- First submitted
- 1 May 2023
- Start date
- 11 Jul 2023
- Primary completion date
- 30 Jul 2028
- Lead sponsor
- Sheba Medical Center
- Diseases
- Melanoma, Glioblastoma
- NCT number
- NCT05909618
What you commit to
- Study type: Interventional · Phase 2
- Planned participants: 33
- From 11 Jul 2023 to the primary completion date, 30 Jul 2028
- 1 site in 1 country
- Visits and tests: ask the trial team, the registry does not list them
Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.
Who cannot take part
Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.
Prior treatment
- Previous life-threatening toxicity to anti-PD-1 antibody monotherapy.
- Previous exposure to Crizanlizumab or any other P-selectin inhibitor.
- Previous or current brain hemorrhage.
- The patient had, or is expected to undergo, allogeneic hematopoietic stem cell transplantation (HSCT).
- Any other severe concurrent disease which, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
- Treatment with other investigational drugs within \<21 days of start of day 1 of the study treatment.
- Any contraindication for treatment with nivolumab according to the product's labels.
- Cohort 2 (Recurrent or Progressive GB) Inclusion Criteria
- Received first line therapy with brain irradiation and maintenance temozolamide.
- Previous life-threatening toxicity to anti-PD-1 antibody monotherapy.
- Previous exposure to Crizanlizumab or any other P-selectin inhibitor.
- Previous or current brain hemorrhage.
- Any other severe concurrent disease which, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
- Treatment with other investigational drugs within \<21 days of start of day 1 of the study treatment.
- Any contraindication for treatment with nivolumab according to the product's labels.
- Cohort 3 (Newly Diagnosed Unmethylated GB) Inclusion Criteria
- Received definitive brain irradiation.
- Patients may be treated with novo TTF (optune) per local standard.
- Previous life-threatening toxicity to anti-PD-1 antibody monotherapy.
- Previous exposure to Crizanlizumab or any other P-selectin inhibitor.
- Previous or current brain hemorrhage.
- Any other severe concurrent disease which, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
- Treatment with other investigational drugs within \<21 days of start of day 1 of the study treatment.
- Any contraindication for treatment with nivolumab according to the product's labels
Other illness
- Systemic steroid therapy for symptomatic brain disease. Note: a dose equivalent to 10 mg prednisone will be allowed
- Auto-immune disease in the last 2 years requiring systemic immune-suppressive therapy.
- Measurable disease per RANO criteria on brain MRI.
- Systemic steroid therapy for symptomatic brain disease. Note: a dose equivalent to 20 mg prednisone will be allowed
- Auto-immune disease in the last 2 years requiring systemic immune-suppressive therapy.
- Systemic steroid therapy for symptomatic brain disease. Note: a dose equivalent to 20 mg prednisone will be allowed
- Auto-immune disease in the last 2 years requiring systemic immune-suppressive therapy.
Lab values
- Adequate organ function defined by blood tests for blood count and chemistry.
- Adequate organ function defined by blood tests for blood count and chemistry.
Age
- Age ≥ 18 years.
- Age ≥ 18 years.
Other
- Have leptomeningeal spread.
- The patient had a contraindication for undergoing brain MRI.
- Pregnant or lactating
- Estimated life expectancy at least 3 months
- Have with recurrent or persistent GB
- Have Eastern Cooperative Oncology Group (ECOG) performance status \<2.
- Women of childbearing potential practicing an acceptable method of birth control.
- Understand study procedures and willingness to comply for the entire duration of the study and to give written informed consent.
- Have leptomeningeal spread.
- The patient had, or is expected to undergo, allogeneic HSCT.
- The patient had a contraindication for undergoing brain MRI.
- Pregnant or lactating
- Estimated life expectancy at least 3 months.
- Histologically confirmed newly diagnosed GB.
- Tumor test result shows MGMT unmethylated type.
- Have Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
- Women of childbearing potential practicing an acceptable method of birth control.
- Understand study procedures and willingness to comply for the entire duration of the study and to give written informed consent.
- Have leptomeningeal spread.
- The patient had, or is expected to undergo, allogeneic HSCT.
- The patient had a contraindication for undergoing brain MRI.
- Be pregnant or lactating
Criteria the registry did not label
- Cohort 1 (MBM) Inclusion Criteria
- Age ≥ 18 years.
- Estimated life expectancy at least 3 months
- Have metastatic melanoma with primarily diagnosed or newly progressing brain metastases.
- Was treated with 1 prior systemic line of immunotherapy - either PD-1 inhibitor monotherapy or combined CTLA4 and PD-1 antibodies or another investigational combination of immunotherapy. Patients with BRAF-mutant melanoma who have also received BRAF mutation targeted therapy are also eligible.
- Have failed prior immunotherapy line, either due to primary resistance or acquired resistance.
- Have measurable disease defined by RECIST criteria and have at least one, non-previously irradiated brain metastasis of at least 1-cm short diameter. Otherwise, previously irradiated lesions should present with enlargement following radiation therapy.
- Is clinically stable with no neurological deficits. Patients may receive steroid supportive therapy up to 10 mg of prednisone or the equivalent.
- Have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
- Adequate organ function defined by blood tests for blood count and chemistry.
- Women of childbearing potential practicing an acceptable method of birth control.
- Understand study procedures and willingness to comply for the entire duration of the study and to give written informed consent.
Age in the registry: 18 years to - · Sex: All · Does not accept healthy volunteers
Sites (1)
Sites in registry order. Pick your city on the disease page to sort them by distance.
| Site | City | Country | Site status |
|---|---|---|---|
| Sheba medical center Coordinator of this site? Confirm its status | Ramat Gan | Israel | Recruiting |
This page is information, not medical advice. Discuss any trial with your doctor.