Neoadjuvant PD-1 in Newly Diagnosed Glioblastoma

Neoadjuvant PD-1 in Newly Diagnosed Glioblastoma: A Phase 2 Clinical Trial

The purpose of this research is to study the safety and efficacy of Camrelizumab treating patients with newly diagnosed glioblastomas.

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma
• Intervention / Treatment: Drug: Camrelizumab; Radiation: radiation; Drug: Temozolomide

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.

• Study Type: Interventional
• Enrollment (Anticipated): 42
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yu Wang, MD; Phone Number: 861069152530; Email: ywang@pumch.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Camrelizumab; Neoadjuvant Camrelizumab 200mg IV, adjuvant Camrelizumab 200mg IV (once every two weeks, until progress); Radiation: radiation; 60Gy/30; Drug: Temozolomide; Given PO during RT 75mg/m2/d; 4 weeks post RT 150-200mg/m2/d days 1-5, 4 weeks/cycle, 6 cycles; Other Names: TMZ

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	up to 12 months
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.	up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with treatment-related adverse events	toxicity assessed by Common Toxicity Criteria (CTC) version	up to 2 years
Objective response rate (ORR)	response rate assessed by Response Assessment in Neuro-Oncology (RANO) criteria	up to 2 years

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Collaborators: Jiangsu HengRui Medicine Co., Ltd.
• Investigators: Principal Investigator: Yu Wang, MD, Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2020
• Primary Completion (Anticipated): December 30, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: September 29, 2020
• First Submitted That Met QC Criteria: October 9, 2020
• First Posted (Actual): October 12, 2020

Study Record Updates

• Last Update Posted (Actual): November 30, 2020
• Last Update Submitted That Met QC Criteria: November 25, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Camrelizumab
• 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: HS-2522

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: There is no IPD share plan.

Drug and device information, study documents

• 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