The Efficacy and Safety of Low-dose Radiotherapy Combined With Sintilimab and Temozolomide in Recurrent Glioblastoma

Official title

Low-dose Radiotherapy Combined With Sintilimab and Temozolomide in Recurrent Glioblastoma: A Single-arm, Prospective Phase II Clinical Study

Overview

This is an open-label, single-arm, phase II clinical trial to explore the efficacy and safety of low-dose radiotherapy combined with programmed death 1 (PD-1) inhibitor (sintilimab) and temozolomide in recurrent glioblastoma. The eligible patients are scheduled to administered sintilimab 200mg D1 Q3W temozolomide 50mg/m2 QD and radiotherapy 1Gy/1F D1/D2/D8/D15 Q3W for 4-6 cycles, then sintilimab for maintenance. The overall primary study hypothesis is that the combination regimen of low-dose radiotherapy, sintilimab and temozolomide is safe and feasible in the treatment of recurrent glioblastoma.

Interventions

• Drug Sintilimab
  Sintilimab 200mg D1, Q3W
• Radiation Low-dose Radiotherapy
  Radiotherapy 1Gy/1F, D1/D2/D8/D15, Q3W

Primary outcome measures

• progression free survival (PFS) [Time frame: from the first day of treatment to the follow up of 1 year]

Secondary outcome measures (2)

• overall survival (OS) [Time frame: from the first day of treatment to the follow up of 1 year]
• Adverse events [Time frame: from the first day of treatment to the follow up of 1 year]

Eligibility criteria

Inclusion criteria

• Histologically confirmed glioblastoma, radiographically or pathologically diagnosed recurrence.
• Aged ≥ 18 years.
• ≥12 weeks after postoperative radiotherapy.
• Karnofsky performance status (KPS) ≥ 60.
• Expected survival > 3 months.
• Adequate organ function, based on meeting all of the following criteria (no blood components and cytologic growth factors were received within 14 days prior to the test):

• Hemoglobin ≥ 90 g/L; absolute neutrophil count ≥ 1.5 × 10\^9/L; and platelet count ≥ 100 × 10\^9/L;
• Serum albumin ≥ 28 g/L;
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN); Alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN;
• Serum creatinine ≤ 1.5 × ULN;
• Activated partial clotting enzyme time and international standardized ratio (INR) ≤ 1.5 × ULN (Patients on stable doses of anticoagulant therapy such as low molecular weight heparin or warfarin with INR within the expected treatment range of anticoagulants can be screened ).
• Thyroid stimulating hormone ≤ ULN; If abnormal, T3 and T4 levels should be examined, and if T3 and T4 levels are normal, they can be screened.
• Subjects voluntarily join the study and sign an informed consent form, with good compliance.

Exclusion criteria

• Treatment with a dose of prednisone > 10mg /d or equivalent dose of corticosteroids is required.
• There exist other uncontrolled central nervous system diseases unrelated to cancer.
• A history of other malignant tumors within the previous 5 years or at the time of enrollment, except for cured skin basal cell carcinoma and cervical in situ cancer, as well as thyroid papilloma.
• Uncontrolled cardiac clinical symptoms or diseases, such as New York Heart Association (NYHA) class II or above heart failure, unstable angina pectoris, myocardial infarction within 1 year, patients with clinically significant supraventricular or ventricular arrhythmia requiring clinical intervention.
• Serious infections, such as severe pneumonia, bacteremia, and infection comorbidities requiring hospitalization, occurred within 4 weeks.
• Active autoimmune diseases, such as interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism; It does not include patients with vitiligo or childhood asthma/allergies that have healed and require no intervention as adults.
• A history of immunodeficiency, including HIV-positive status or other acquired congenital immunodeficiency diseases, or a history of organ transplantation and bone marrow transplantation.
• Patients with active tuberculosis infection found by history or CT examination, or patients with active tuberculosis infection history within 1 year prior to enrollment, or patients with active tuberculosis infection history before 1 year without formal treatment.
• Active hepatitis B (HBV DNA ≥ 2,000 IU/mL or 10,000 copies/mL) or hepatitis C (positive HCV antibody test and HCV RNA above the lower limit of detection).
• Known history of psychotropic drug abuse, alcoholism and drug use.
• Not suitable for inclusion, as judged by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Yingpeng Peng — Zhuhai

Identifiers

NCT: NCT06220552 · ZDWY.TJBZLK.003

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗