A Large-scale Research for Immunotherapy of Glioblastoma With Autologous Heat Shock Protein gp96

This trial is to further study the safety and effectiveness of autologous gp96 treatment of glioblastoma on the basis of preliminary work.

Study Overview

• Status: Recruiting
• Conditions: Glioma of Brain
• Intervention / Treatment: Biological: gp96; Drug: Temozolomide; Radiation: radiotherapy

Detailed Description

RATIONALE: heat shock protein gp96-peptide complex made from a person's tumor cells may help the body build an effective immune response to kill tumor cells.

Overall Goals:

- to evaluate the safety and induction of anti-tumor immunity by administration of an immunogenic human tumor cell vaccine, and assess immune response in relation to clinical outcome.

Primary Aim:

- to further evaluate effectiveness of autologous gp96 treatment of glioblastoma on the basis of preliminary work.

Secondary Aims:

to study the immune response to vaccination, to monitor clinical responses , to further the safety of vaccine.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: zhixian Gao, Doctor; Phone Number: 086-13810876745; Email: zhixian_g@hotmail.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100050
      • Recruiting
      • Beijing Tiantan Hospital Affiliated to Capital Medical University
      • Contact: hua Gao; Phone Number: 18600678822; Email: gh2004518@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Able to read and understand the informed consent document; must sign the informed consent;
2. Aged 18 to 75 years old , sex is not limited;
3. Newly Diagnosed supratentoria glioma, Must have undergone a at least a 80% resection;
4. Availability of at least 4 g tumor sample;
5. Patient must receive concurrent chemoradiotherapy (temozolomide chemotherapy and radiotherapy).
6. Karnofsky functional status rating > or equal to 70.
7. Adequate bone marrow function including the absence of lymphopenia (ANC > 1,500/ mm3; Hemoglobin > 10g/dL ; platelet count >100,000/mm3), adequate liver function (serum glutamic oxaloacetic transaminase/ aspartate aminotransferase [AST], alanine amino transferase [ALT] <2.5 times institutional upper limit of normals [IULNs] ), and adequate renal function (BUN and creatinine <1.5 times IULNs)
8. Agree to Surgical indications of Heart & lung and without the coagulation system disease
9. Except for surgery and radiotherapy and chemotherapy before vaccine treatment, no other cancer treatment is received.

Exclusion Criteria:

1. Inability to comply with study-related procedures
2. Unavailability of at least 6 doses of vaccine
3. Severe allergies
4. Unstable or severe intercurrent medical conditions
5. Current diagnosis of Human Immunodeficiency Virus and Patients with active uncontrolled infection.
6. patients with any systemic disease needed to be treated with immunosuppressant or Corticosteroids.
7. any other clinical trials within 30 days pre-vaccination.
8. Female patients who are pregnant or breastfeeding
9. Carmustine extended release implant surgery within 6 months
10. Steroidal drugs are currently being used systemically.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: gp96 group; Patients receive standard treatment with radiation and temozolomide after surgery. Then 6 times of autologous gp96 vaccination are administered via subcutaneous injection in 25μg doses at the 2nd week after the end of postoperative radiotherapy. ( gp96 is administered once a week for the first 4 weeks, the 5th injection is administered 2 weeks after the 4th injection, and the 6th injection is administered 3 weeks after the 5th injection. ) The first adjunctive temozolomide startes on the day of the fifth gp96 injection. (150-200 mg/m2/day for 5 days, then stop for 23 days, one cycle is 28 days for a total of 6 cycles)	Biological: gp96; 25 mcg IH; Other Names: Heat Shock; HSPPC-96; Drug: Temozolomide; temozolomide monotherapy (150-200 mg / m2 / day for 5 days, then discontinuance for 23 days , 28 days for a a cycle, a total of 6 cycles ).; Other Names: TZM; Radiation: radiotherapy; Stupp regimen of radiotherapy
Active Comparator: control group; Patients receive standard treatment with radiation and temozolomide after surgery. Then only adjuvant treatment with temozolomide is administered.	Drug: Temozolomide; temozolomide monotherapy (150-200 mg / m2 / day for 5 days, then discontinuance for 23 days , 28 days for a a cycle, a total of 6 cycles ).; Other Names: TZM; Radiation: radiotherapy; Stupp regimen of radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
1-year survival rate	1 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival		5 years
Progression-free survival		5 years
Progression-free survival rate		1 year
Number of participants with adverse events related to gp96 immunotherapy	A complete blood count will be requested before the first vaccination, after the second vaccination and after the last vaccination to monitor the side effect of gp96 immunotherapy. And blood chemistries will also be requested at the same time point for the same reason.And other adverse events related to gp96 immunotherapy will be recorded according to the NCI-CTCAE 5.0 criteria.	up to 3 months after vaccine completion
changes in antigen specific T cells	tumor antigen specific T cells are determined by IFN-γ Enzyme-linked Tumor antigen specific T cells will be determined by IFN-γ Enzyme-linked immunosorbent spot using the autologous tumor cell lysis as the antigen.	within 3 days before the first vaccination and within 10 days after the last vaccination

Collaborators and Investigators

• Sponsor: Cure&Sure Biotech Co., LTD
• Collaborators: Beijing Tiantan Hospital; Shenzhen Second People's Hospital
• Investigators: Principal Investigator: zhixian Gao, Doctor, Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 21, 2019
• Primary Completion (Anticipated): August 20, 2021
• Study Completion (Anticipated): August 20, 2024

Study Registration Dates

• First Submitted: August 22, 2018
• First Submitted That Met QC Criteria: August 24, 2018
• First Posted (Actual): August 28, 2018

Study Record Updates

• Last Update Posted (Actual): March 12, 2020
• Last Update Submitted That Met QC Criteria: March 10, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: supratentorial glioma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: CS-TT-G-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes