Actively Recruiting

Phase 2
Age: 18Years +
All Genders
NCT05909618

Crizanlizumab Alone or in Combination With Nivolumab for Glioblastoma and Melanoma With Brain Metastases

Led by Sheba Medical Center · Updated on 2025-07-22

33

Participants Needed

1

Research Sites

368 weeks

Total Duration

On this page

Sponsors

S

Sheba Medical Center

Lead Sponsor

P

Prof. Ronit Satchi-Fainaro, Director, Cancer Biology Research Center, Tel Aviv University, Tel Aviv, Israel.

Collaborating Sponsor

AI-Summary

What this Trial Is About

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.

CONDITIONS

Official Title

Crizanlizumab Alone or in Combination With Nivolumab for Glioblastoma and Melanoma With Brain Metastases

Who Can Participate

Age: 18Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Age 18 years or older
  • Estimated life expectancy of at least 3 months
  • For metastatic melanoma cohort: metastatic melanoma with newly diagnosed or progressing brain metastases
  • Prior immunotherapy received for metastatic melanoma, including PD-1 inhibitors or combined CTLA4 and PD-1 antibodies
  • Failed prior immunotherapy due to resistance
  • Measurable disease per RECIST or RANO criteria with at least one brain metastasis of at least 1 cm or progression of previously irradiated lesions
  • Clinically stable with no neurological deficits; steroids allowed up to 10 mg prednisone or equivalent
  • ECOG performance status 0 or 1 for melanoma cohort; ECOG less than 2 for glioblastoma cohorts
  • Adequate organ function based on blood tests
  • For newly diagnosed glioblastoma cohort: histologically confirmed GB with unmethylated MGMT promoter
  • Received definitive brain radiation
  • Women of childbearing potential practicing acceptable birth control
  • Understand study procedures and willing to comply for entire study duration and provide written informed consent
Not Eligible

You will not qualify if you...

  • Systemic steroid therapy for symptomatic brain disease above allowed doses (10 mg prednisone for melanoma cohort; 20 mg prednisone for glioblastoma cohorts)
  • Leptomeningeal spread
  • Previous life-threatening toxicity to anti-PD-1 antibody monotherapy
  • Autoimmune disease in the last 2 years requiring systemic immune-suppressive therapy
  • Previous exposure to crizanlizumab or other P-selectin inhibitors
  • Previous or current brain hemorrhage
  • History of or expected allogeneic hematopoietic stem cell transplantation
  • Contraindication for brain MRI
  • Any other severe concurrent disease making participant inappropriate for study
  • Pregnant or lactating
  • Treatment with other investigational drugs within 21 days before study treatment start
  • Any contraindication for nivolumab treatment according to product labels

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Trial Site Locations

Total: 1 location

1

Sheba medical center

Ramat Gan, Israel, Israel

Actively Recruiting

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Research Team

R

Ronnie Shapira Frommer, Dr

CONTACT

M

Meital Bar

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NON_RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

3

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