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Neoadjuvant PD-1 in Newly Diagnosed Glioblastoma

Primary Purpose

Glioblastoma

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Camrelizumab
radiation
Temozolomide
Sponsored by
Peking Union Medical College Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma focused on measuring Camrelizumab

Eligibility Criteria

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

Inclusion Criteria:

  1. Patient must be willing to provide informed consent.
  2. Patient must be 18-70 years old.
  3. Patient must be first diagnosed of WHO grade IV neural glioma by MRI, without previous treatment.
  4. Patient must receive confine operation that can be delayed for at least 2 weeks, in order to receive neoadjuvant treatment; patient must not receive other antitumor therapy besides this study plan.
  5. Karnofsky ≥ 70
  6. If patient is on glucocorticoids treatment, the amount of glucocorticoids must be stable or decreasing at least 5 days before baseline MRI acquisition. Oral dexamethasone must be <3 tablets(0.75mg/tablet) at least 5 days before baseline MRI.
  7. Patient has not received antibiotics for 1month before inclusion.
  8. Estimate survival ≥12weeks.
  9. Major organ functions normally, without severe blood, heart, lung, liver, renal abnormality or immune deficiency. Laboratory examination meets the following requirements:

    i. Complete blood count:

    1. HGB≥90g/L;
    2. WBC≥3.0×109/L, NEUT≥1.5×109/L;
    3. PLT ≥60×109/L;

    ii. Blood biochemistry:

    1. BIL≤1.5×upper limit of normal (ULN);
    2. ALT and AST≤2.0×ULN;
    3. Serum Cr≤1.5×ULN or Ccr≥50ml/min (Cockcroft-Gault formular);

    iii. Fecal occult blood(-);

    iv. Urine routines normal, or urine protein <(++), or 24h urine protein<1.0g;

    v. Left ventricular ejection fraction(LVEF)≥50%.

  10. Normal clotting function, no active bleeding or thrombosis disease.

    1. INR≤1.5×ULN;
    2. APTT≤1.5×ULN;
    3. PT≤1.5ULN;
  11. Female patients of childbearing potential must receive pregnancy test (serum or urine) with negative result, and voluntarily practice appropriate forms of contraception, during observation period and 8 weeks after final administration of Camrelizumab; male patients should receive surgical sterilization or agree to practice appropriate forms of contraception, during observation period and 8 weeks after final administration of Camrelizumab.
  12. Patient should have good follow-up compliance.

Exclusion Criteria:

  1. Patient with other malignant tumor history in five years (except complete treatment of cervical cancer in situ, basal cell carcinoma, squamous cell skin cancer).
  2. Patient needs emergency surgery.
  3. History of allergy to other monoclonal antibody or other ingredients; or can not receive MRI.
  4. Previous immunotherapy (e.g. PD-1, PD-L1, CTLA-4), previous intracranial radiotherapy.
  5. Any previous investigational medication within 4 weeks before first administration of Camrelizumab.
  6. Included in another clinical investigation simultaneously, except for observational (non-interventional) clinical study or follow-up of an interventional clinical study.
  7. Already has meningioma, multiple gliomas, extracranial lesions. The definition of multiple gliomas is: discontinuous strong signal on T2/FLAIR; satellite lesions.
  8. History of antitumor vaccine injection, or history of live vaccine injection within 4 weeks before first administration of Camrelizumab.
  9. Less than 4 weeks after the latest surgery, radiochemotherapy, glucocorticoids treatment, immunotherapy, targeted therapy.
  10. Thrombosis event within 12 months before inclusion, such as cerebrovascular accident (TIA, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, pulmonary embolism.
  11. Any unstable systematic disease (including active infection, uncontrolled hypertension, unstable angina, medical treatment needed liver, kidney, metabolic disease).
  12. Heart failure with NYHA grade 2 or above, unstable angina, myocardial infarction within 1 year, treatment needed supraventricular or ventricular arrhythmia.
  13. Patient with known HIV infection or active hepatitis.
  14. History or risk of autoimmune disease, such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, glomerulonephritis. Patient is allowed to be included, if eczema, psoriasis or leukoderma is well controlled at baseline, with only local weak steroid treatment.
  15. Systematic immune suppressor, such as prednisone, cyclophosphamide, amethopterin, azathioprim, thalidomide, anti-TNF drugs. Low dose of systematic immune suppressor is allowed (e.g. single dose of dexamethasone for nausea). Patient with postural hypotension or adrenocortical insufficiency is allowed to use inhaled corticosteroids and mineralocorticoid.
  16. History of interstitial lung disease, idiopathic pulmonary fibrosis, pneumonia, tissue pneumonia, or evidence of active pneumonia on CT scan. Radiation pneumonia or pulmonary fibrosis is allowed in patient with radiation history.
  17. Other chronic disease that requires immune suppressor or corticosteroids treatment.
  18. Female patients who are pregnant or currently breastfeeding.
  19. Active infection or fever of unknown origin >38.5℃ at the first administration of Camrelizumab.
  20. Blood clotting abnormality, bleeding tendency or receiving thrombolytic or anticoagulant therapy.
  21. Patient with known history of Psychotropic drug abuse, alcoholism or drug addiction.
  22. Other situation determined by the researcher that may influence the conduction or result of the clinical study.

Sites / Locations

  • Peking Union Medical College HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Neoadjuvant PD-1 inhibitor

Arm Description

Neoadjuvant PD-1 inhibitor Camrelizumab will be administered to patients with newly diagnosed glioblastomas, followed by surgical resection, standard radiochemotherapy, and further PD-1 inhibitor treatment.

Outcomes

Primary Outcome Measures

Overall survival (OS)
Survival will be assessed at 6 months and 12 months from the time of recruitment until the time of death. Kaplan-Meier survival analyses will be performed.
Progression-free survival (PFS)
Progression-free survival will be assessed at 6 months and 12 months from the time of recruitment until the time of death. Kaplan-Meier survival analyses will be performed.

Secondary Outcome Measures

Proportion of participants with treatment-related adverse events
toxicity assessed by Common Toxicity Criteria (CTC) version
Objective response rate (ORR)
response rate assessed by Response Assessment in Neuro-Oncology (RANO) criteria

Full Information

First Posted
September 29, 2020
Last Updated
November 25, 2020
Sponsor
Peking Union Medical College Hospital
Collaborators
Jiangsu HengRui Medicine Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT04583020
Brief Title
Neoadjuvant PD-1 in Newly Diagnosed Glioblastoma
Official Title
Neoadjuvant PD-1 in Newly Diagnosed Glioblastoma: A Phase 2 Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
November 2020
Overall Recruitment Status
Recruiting
Study Start Date
November 12, 2020 (Actual)
Primary Completion Date
December 30, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Peking Union Medical College Hospital
Collaborators
Jiangsu HengRui Medicine Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No

5. Study Description

Brief Summary
The purpose of this research is to study the safety and efficacy of Camrelizumab treating patients with newly diagnosed glioblastomas.
Detailed Description
This is a phase II clinical trial. The purpose of this research is to study the safety and efficacy of Camrelizumab treating patients with newly diagnosed glioblastomas. Neoadjuvant PD-1 inhibitor will be administered to patients with newly diagnosed glioblastomas, followed by surgical resection, standard radiochemotherapy, and further PD-1 inhibitor treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma
Keywords
Camrelizumab

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Neoadjuvant PD-1 inhibitor will be administered to patients with newly diagnosed glioblastomas, followed by surgical resection, standard radiochemotherapy, and further PD-1 inhibitor treatment
Masking
None (Open Label)
Allocation
N/A
Enrollment
42 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Neoadjuvant PD-1 inhibitor
Arm Type
Experimental
Arm Description
Neoadjuvant PD-1 inhibitor Camrelizumab will be administered to patients with newly diagnosed glioblastomas, followed by surgical resection, standard radiochemotherapy, and further PD-1 inhibitor treatment.
Intervention Type
Drug
Intervention Name(s)
Camrelizumab
Intervention Description
Neoadjuvant Camrelizumab 200mg IV, adjuvant Camrelizumab 200mg IV (once every two weeks, until progress)
Intervention Type
Radiation
Intervention Name(s)
radiation
Intervention Description
60Gy/30
Intervention Type
Drug
Intervention Name(s)
Temozolomide
Other Intervention Name(s)
TMZ
Intervention Description
Given PO during RT 75mg/m2/d; 4 weeks post RT 150-200mg/m2/d days 1-5, 4 weeks/cycle, 6 cycles
Primary Outcome Measure Information:
Title
Overall survival (OS)
Description
Survival will be assessed at 6 months and 12 months from the time of recruitment until the time of death. Kaplan-Meier survival analyses will be performed.
Time Frame
up to 12 months
Title
Progression-free survival (PFS)
Description
Progression-free survival will be assessed at 6 months and 12 months from the time of recruitment until the time of death. Kaplan-Meier survival analyses will be performed.
Time Frame
up to 12 months
Secondary Outcome Measure Information:
Title
Proportion of participants with treatment-related adverse events
Description
toxicity assessed by Common Toxicity Criteria (CTC) version
Time Frame
up to 2 years
Title
Objective response rate (ORR)
Description
response rate assessed by Response Assessment in Neuro-Oncology (RANO) criteria
Time Frame
up to 2 years

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: Patient must be willing to provide informed consent. Patient must be 18-70 years old. Patient must be first diagnosed of WHO grade IV neural glioma by MRI, without previous treatment. Patient must receive confine operation that can be delayed for at least 2 weeks, in order to receive neoadjuvant treatment; patient must not receive other antitumor therapy besides this study plan. Karnofsky ≥ 70 If patient is on glucocorticoids treatment, the amount of glucocorticoids must be stable or decreasing at least 5 days before baseline MRI acquisition. Oral dexamethasone must be <3 tablets(0.75mg/tablet) at least 5 days before baseline MRI. Patient has not received antibiotics for 1month before inclusion. Estimate survival ≥12weeks. Major organ functions normally, without severe blood, heart, lung, liver, renal abnormality or immune deficiency. Laboratory examination meets the following requirements: i. Complete blood count: HGB≥90g/L; WBC≥3.0×109/L, NEUT≥1.5×109/L; PLT ≥60×109/L; ii. Blood biochemistry: BIL≤1.5×upper limit of normal (ULN); ALT and AST≤2.0×ULN; Serum Cr≤1.5×ULN or Ccr≥50ml/min (Cockcroft-Gault formular); iii. Fecal occult blood(-); iv. Urine routines normal, or urine protein <(++), or 24h urine protein<1.0g; v. Left ventricular ejection fraction(LVEF)≥50%. Normal clotting function, no active bleeding or thrombosis disease. INR≤1.5×ULN; APTT≤1.5×ULN; PT≤1.5ULN; Female patients of childbearing potential must receive pregnancy test (serum or urine) with negative result, and voluntarily practice appropriate forms of contraception, during observation period and 8 weeks after final administration of Camrelizumab; male patients should receive surgical sterilization or agree to practice appropriate forms of contraception, during observation period and 8 weeks after final administration of Camrelizumab. Patient should have good follow-up compliance. Exclusion Criteria: Patient with other malignant tumor history in five years (except complete treatment of cervical cancer in situ, basal cell carcinoma, squamous cell skin cancer). Patient needs emergency surgery. History of allergy to other monoclonal antibody or other ingredients; or can not receive MRI. Previous immunotherapy (e.g. PD-1, PD-L1, CTLA-4), previous intracranial radiotherapy. Any previous investigational medication within 4 weeks before first administration of Camrelizumab. Included in another clinical investigation simultaneously, except for observational (non-interventional) clinical study or follow-up of an interventional clinical study. Already has meningioma, multiple gliomas, extracranial lesions. The definition of multiple gliomas is: discontinuous strong signal on T2/FLAIR; satellite lesions. History of antitumor vaccine injection, or history of live vaccine injection within 4 weeks before first administration of Camrelizumab. Less than 4 weeks after the latest surgery, radiochemotherapy, glucocorticoids treatment, immunotherapy, targeted therapy. Thrombosis event within 12 months before inclusion, such as cerebrovascular accident (TIA, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, pulmonary embolism. Any unstable systematic disease (including active infection, uncontrolled hypertension, unstable angina, medical treatment needed liver, kidney, metabolic disease). Heart failure with NYHA grade 2 or above, unstable angina, myocardial infarction within 1 year, treatment needed supraventricular or ventricular arrhythmia. Patient with known HIV infection or active hepatitis. History or risk of autoimmune disease, such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, glomerulonephritis. Patient is allowed to be included, if eczema, psoriasis or leukoderma is well controlled at baseline, with only local weak steroid treatment. Systematic immune suppressor, such as prednisone, cyclophosphamide, amethopterin, azathioprim, thalidomide, anti-TNF drugs. Low dose of systematic immune suppressor is allowed (e.g. single dose of dexamethasone for nausea). Patient with postural hypotension or adrenocortical insufficiency is allowed to use inhaled corticosteroids and mineralocorticoid. History of interstitial lung disease, idiopathic pulmonary fibrosis, pneumonia, tissue pneumonia, or evidence of active pneumonia on CT scan. Radiation pneumonia or pulmonary fibrosis is allowed in patient with radiation history. Other chronic disease that requires immune suppressor or corticosteroids treatment. Female patients who are pregnant or currently breastfeeding. Active infection or fever of unknown origin >38.5℃ at the first administration of Camrelizumab. Blood clotting abnormality, bleeding tendency or receiving thrombolytic or anticoagulant therapy. Patient with known history of Psychotropic drug abuse, alcoholism or drug addiction. Other situation determined by the researcher that may influence the conduction or result of the clinical study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yu Wang, MD
Phone
861069152530
Email
ywang@pumch.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yu Wang, MD
Organizational Affiliation
Peking Union Medical College Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Peking Union Medical College Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100730
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yu Wang, MD

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
There is no IPD share plan.

Learn more about this trial

Neoadjuvant PD-1 in Newly Diagnosed Glioblastoma

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