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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

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:

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.

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

NCT ID

NCT04888611

First Posted

May 12, 2021

Last Updated

November 28, 2021

Sponsor

Huashan Hospital

Collaborators

Jiangsu HengRui Medicine Co., Ltd., Shanghai Sunstem Biotechnology Co., Ltd.

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

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

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

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

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

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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