Neoadjuvant PD-1 in Newly Diagnosed Glioblastoma

NCT ID: NCT04583020

Last Updated: 2020-11-30

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-12
• Study Completion Date: 2023-12-31

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.

Conditions

Glioblastoma

Keywords

Camrelizumab

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Neoadjuvant PD-1 inhibitor

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.

Group Type: EXPERIMENTAL

Camrelizumab

Intervention Type: DRUG

Neoadjuvant Camrelizumab 200mg IV, adjuvant Camrelizumab 200mg IV (once every two weeks, until progress)

radiation

Intervention Type: RADIATION

60Gy/30

Temozolomide

Intervention Type: DRUG

Given PO during RT 75mg/m2/d; 4 weeks post RT 150-200mg/m2/d days 1-5, 4 weeks/cycle, 6 cycles

Interventions

Camrelizumab

Neoadjuvant Camrelizumab 200mg IV, adjuvant Camrelizumab 200mg IV (once every two weeks, until progress)

Intervention Type: DRUG

radiation

60Gy/30

Intervention Type: RADIATION

Temozolomide

Given PO during RT 75mg/m2/d; 4 weeks post RT 150-200mg/m2/d days 1-5, 4 weeks/cycle, 6 cycles

Intervention Type: DRUG

Other Intervention Names

TMZ

Eligibility Criteria

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.

• 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

Peking Union Medical College Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yu Wang, MD

Role: PRINCIPAL_INVESTIGATOR

Peking Union Medical College Hospital

Locations

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yu Wang, MD

Role: CONTACT

Phone: 861069152530

Email: ywang@pumch.cn

Facility Contacts

Yu Wang, MD

Role: primary

Other Identifiers

HS-2522

Identifier Type: -

Identifier Source: org_study_id