Neoadjuvant PD-1 Antibody Alone or Combined With DC Vaccines for Recurrent Glioblastoma

NCT04888611 | Unknown Phase 2

• 1 other identifier: KY2021-547
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Glioblastoma multiforme (GBM) are the most prevalent malignant tumor in central nervous system. At recurrence, no clear standard-of-care therapy is agreed for recurrent GBM (rGBM) and median overall survival is estimated to rarely exceed 6-9 months with effective therapies. Neoadjuvant therapy with anti-PD-1 monoclonal antibodies were confirmed to be helpful to extend survival in rGBM. Vaccine, dendritic cells (DCs) pulsed with glioblastoma stem-like cell (GSC) antigens (GSC-DCV), could extend survival for GBM patients in our previous clinical study (PMID: 30159779). The purpose of this study is to evaluate the safety and efficiency of using the neoadjuvant therapy with PD-1 antibody (Carilizumab) plus DC vaccine (GSC-DCV) in patients with recurrent glioblastoma.

Conditions

Recurrent Glioblastoma

Keywords

Glioblastoma; PD-1 antibody; DC vaccine; Immunotherapy

Outcome Measures

Primary Outcomes (2)

• Overall survival (OS)

  Time from enrollment to the dates of death from any cause or last follow up reported

  24 months

• Progression-free survival (PFS)

  Time from enrollment to the dates of disease progression, death from any cause or last tumor assessment reported between date of first patient enrollment

  12 months

Secondary Outcomes (2)

• Number of treatment-related adverse events

  12 months

• Treatment Responses Rate

  6 months

Other Outcomes (1)

• Exploratory biomarkers

  24 months

Study Arms (2)

Neoadjuvant PD-1 inhibitor plus DC vaccine

EXPERIMENTAL

Patients will receive neoadjuvant Camrelizumab (PD-1 antibody), followed by surgical resection, DC vaccines and further PD-1 inhibitor treatment until toxicity or progression.

Biological: Camrelizumab plus GSC-DCV

Neoadjuvant PD-1 inhibitor plus Placebo

ACTIVE COMPARATOR

Patients will receive neoadjuvant Camrelizumab (PD-1 antibody), followed by surgical resection, placebo and further PD-1 inhibitor treatment until toxicity or progression.

Biological: Camrelizumab plus Placebo

Interventions

Camrelizumab plus GSC-DCV BIOLOGICAL

Prior to scheduled surgery, patients need to receive Camrelizumab IV (3mg/kg, up to 200mg). After surgery, patients receive Camrelizumab IV (3mg/kg, up to 200mg) and GSC-DCV IH every 3 weeks in the absence of disease progression or unacceptable toxicity.

Neoadjuvant PD-1 inhibitor plus DC vaccine

Camrelizumab plus Placebo BIOLOGICAL

Prior to scheduled surgery, patients need to receive Camrelizumab IV (3mg/kg, up to 200mg). After surgery, patients receive Camrelizumab IV (3mg/kg, up to 200mg) and Placebo IH every 3 weeks in the absence of disease progression or unacceptable toxicity.

Neoadjuvant PD-1 inhibitor plus Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age from 18 to 70 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2.
• Estimated life expectancy \> 3 months.
• Previous first-line therapy with radiotherapy and chemotherapy, first or second relapse with unequivocal evidence of tumor progression.
• Pathological diagnosis or molecular diagnosis for lesion this time was confirmed to be recurrent brain glioma (WHO grade 4).
• Patients with subtotal resection or above of the tumor confirmed with contrast MR within 72 hours after surgery.
• No high-dose systemic corticosteroids (defined as \>10 mg day-1 of prednisone or bio-equivalent for at least seven consecutive days before administration).
• No antibiotics for at least three consecutive days before administration.
• Adequate organ function defined by:
• Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) ≥ 1.0×10\^9/L, platelets ≥100×10\^9/L; hemoglobin ≥ 8 g/dL. Hepatic: bilirubin 2×upper limit of normal (ULN), aspartate transaminase (AST) and alanine transaminase (ALT) \< 2.5×upper limit of normal (ULN). Renal: Normal serum Creatinine for age (below) or creatinine clearance \>60 ml/min/1.73 m2. Electrocardiogram: normal.
• Written informed consent.
• Patient should have good follow-up compliance.

You may not qualify if:

• Pregnant or breast-feeding patients.
• Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients with history of immune system abnormalities such as hyperimmunity (e.g., autoimmune diseases) and hypoimmunity (e.g., myelodysplastic disorders, marrow failures, AIDS, ongoing pregnancy, transplant immuno-suppression), or medication of cortisol.
• Patients with any conditions that could potentially alter immune function (e.g., AIDS, multiple sclerosis, diabetes, renal failure).
• Any previous investigational medication within 30 days before first administration of Camrelizumab.
• History of allergy to study drug components or of severe hypersensitivity reactions to any monoclonal antibodies.

Sponsors & Collaborators

• Huashan Hospital: lead
• Jiangsu HengRui Medicine Co., Ltd.: collaborator
• Shanghai Sunstem Biotechnology Co., Ltd.: collaborator

Study Sites (1)

Huashan Hospital, Fudan University

Shanghai, Shanghai Municipality, 200040, China

RECRUITING

MeSH Terms

Conditions

Glioblastoma

Interventions

camrelizumab

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Central Study Contacts

Yu Yao, MD

CONTACT

86-021-52889999; yu_yao@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: May 12, 2021
• First Posted: May 17, 2021
• Study Start: October 26, 2021
• Primary Completion: May 1, 2023
• Study Completion: May 1, 2024
• Last Updated: November 30, 2021

Record last verified: 2021-11

Locations

CN (1)