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

NCT ID: NCT04888611

Last Updated: 2021-11-30

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-26
• Study Completion Date: 2024-05-01

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.

Detailed Description

This is a phase II randomized controlled clinical study. The purpose of this research is to study the safety and efficacy of Camrelizumab alone or combined with GSC-DCV vaccines in treating patients with recurrent glioblastomas. The participants will be randomly assigned into two group. Patients in group A will receive neoadjuvant Camrelizumab (PD-1 antibody), followed by surgical resection, DC vaccines and further PD-1 inhibitor treatment until toxicity or progression. Patients in group B will receive neoadjuvant Camrelizumab (PD-1 antibody), followed by surgical resection, placebo and further PD-1 inhibitor treatment until toxicity or progression. Furthermore, to evaluate the associations between exploratory biomarkers, clinical outcomes, and adverse events based on the next generation sequencing.

Conditions

Recurrent Glioblastoma

Keywords

Glioblastoma; PD-1 antibody; DC vaccine; Immunotherapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Neoadjuvant PD-1 inhibitor plus DC vaccine

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

Group Type: EXPERIMENTAL

Camrelizumab plus GSC-DCV

Intervention Type: 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 Placebo

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

Group Type: ACTIVE_COMPARATOR

Camrelizumab plus Placebo

Intervention Type: 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.

Interventions

Camrelizumab plus GSC-DCV

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.

Intervention Type: BIOLOGICAL

Camrelizumab plus Placebo

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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Age from 18 to 70 years.

2. Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2.

3. Estimated life expectancy > 3 months.

4. Previous first-line therapy with radiotherapy and chemotherapy, first or second relapse with unequivocal evidence of tumor progression.

5. Pathological diagnosis or molecular diagnosis for lesion this time was confirmed to be recurrent brain glioma (WHO grade 4).

6. Patients with subtotal resection or above of the tumor confirmed with contrast MR within 72 hours after surgery.

7. No high-dose systemic corticosteroids (defined as >10 mg day-1 of prednisone or bio-equivalent for at least seven consecutive days before administration).

8. No antibiotics for at least three consecutive days before administration.

9. 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.

10. Written informed consent.

11. Patient should have good follow-up compliance.

Exclusion Criteria

1. Pregnant or breast-feeding patients.

2. 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.

3. 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.

4. Patients with any conditions that could potentially alter immune function (e.g., AIDS, multiple sclerosis, diabetes, renal failure).

5. Any previous investigational medication within 30 days before first administration of Camrelizumab.

6. History of allergy to study drug components or of severe hypersensitivity reactions to any monoclonal antibodies.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jiangsu HengRui Medicine Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Shanghai Sunstem Biotechnology Co., Ltd.

UNKNOWN

Sponsor Role: collaborator

Huashan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Yu Yao, MD

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Huashan Hospital, Fudan University

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yu Yao, MD

Role: CONTACT

Phone: 86-021-52889999

Email: yu_yao@fudan.edu.cn

Facility Contacts

Yu Yao, MD

Role: primary

Other Identifiers

KY2021-547

Identifier Type: -

Identifier Source: org_study_id