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

Primary Purpose

Recurrent Glioblastoma

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Camrelizumab plus GSC-DCV
Camrelizumab plus Placebo
Sponsored by
Huashan Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Glioblastoma focused on measuring Glioblastoma, PD-1 antibody, DC vaccine, Immunotherapy

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Huashan Hospital, Fudan UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Neoadjuvant PD-1 inhibitor plus DC vaccine

Neoadjuvant PD-1 inhibitor plus Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

Overall survival (OS)
Time from enrollment to the dates of death from any cause or last follow up reported
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

Secondary Outcome Measures

Number of treatment-related adverse events
Toxicity assessed by Common Terminology Criteria for Adverse Events
Treatment Responses Rate
Response rate assessed by immunotherapy Response Assessment for Neuro-Oncology (iRANO) criteria

Full Information

First Posted
May 12, 2021
Last Updated
November 28, 2021
Sponsor
Huashan Hospital
Collaborators
Jiangsu HengRui Medicine Co., Ltd., Shanghai Sunstem Biotechnology Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT04888611
Brief Title
Neoadjuvant PD-1 Antibody Alone or Combined With DC Vaccines for Recurrent Glioblastoma
Official Title
Neoadjuvant PD-1 Antibody Alone or Combined With Autologous Glioblastoma Stem-like Cell Antigens-primed DC Vaccines (GSC-DCV) for Patients With Recurrent Glioblastoma:A Phase II, Randomized Controlled, Double Blind Clinical Trial.
Study Type
Interventional

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Recruiting
Study Start Date
October 26, 2021 (Actual)
Primary Completion Date
May 1, 2023 (Anticipated)
Study Completion Date
May 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Huashan Hospital
Collaborators
Jiangsu HengRui Medicine Co., Ltd., Shanghai Sunstem Biotechnology Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Glioblastoma
Keywords
Glioblastoma, PD-1 antibody, DC vaccine, Immunotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Neoadjuvant PD-1 inhibitor plus DC vaccine
Arm Type
Experimental
Arm Description
Patients will receive neoadjuvant Camrelizumab (PD-1 antibody), followed by surgical resection, DC vaccines and further PD-1 inhibitor treatment until toxicity or progression.
Arm Title
Neoadjuvant PD-1 inhibitor plus Placebo
Arm Type
Active Comparator
Arm Description
Patients will receive neoadjuvant Camrelizumab (PD-1 antibody), followed by surgical resection, placebo and further PD-1 inhibitor treatment until toxicity or progression.
Intervention Type
Biological
Intervention Name(s)
Camrelizumab plus GSC-DCV
Intervention Description
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
Intervention Name(s)
Camrelizumab plus Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Overall survival (OS)
Description
Time from enrollment to the dates of death from any cause or last follow up reported
Time Frame
24 months
Title
Progression-free survival (PFS)
Description
Time from enrollment to the dates of disease progression, death from any cause or last tumor assessment reported between date of first patient enrollment
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Number of treatment-related adverse events
Description
Toxicity assessed by Common Terminology Criteria for Adverse Events
Time Frame
12 months
Title
Treatment Responses Rate
Description
Response rate assessed by immunotherapy Response Assessment for Neuro-Oncology (iRANO) criteria
Time Frame
6 months
Other Pre-specified Outcome Measures:
Title
Exploratory biomarkers
Description
To investigate the association between biomarkers and clinical outcomes using diverse biospecimen based on the next generation sequencing, including ctDNA, TIL (tumor infiltrating lymphocyte) density and TCR (T cell receptor) Clonality, gene expression signature, genomic mutation, microbial bacteria and so on.
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yu Yao, MD
Phone
86-021-52889999
Email
yu_yao@fudan.edu.cn
Facility Information:
Facility Name
Huashan Hospital, Fudan University
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200040
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yu Yao, MD
Phone
86-021-5288-9999
Email
yu_yao@fudan.edu.cn
First Name & Middle Initial & Last Name & Degree
Liangfu Zhou, MD

12. IPD Sharing Statement

Learn more about this trial

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

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