Study of AK105 With Anlotinib and Radiotherapy Adjuvant Therapy in MGMT Unmethylated Newly Diagnosed Glioblastoma.

NCT05033587 | Unknown Phase 2

• 1 other identifier: 2021-252-02
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, open-label single-arm, exploratory, two-stage design trial, aiming to investigate safety and efficacy of AK105 with anlotinib and radiotherapy adjuvant therapy in MGMT unmethylated newly diagnosed glioblastoma.

Conditions

MGMT-Unmethylated Glioblastoma

Outcome Measures

Primary Outcomes (1)

• PFSR-6m

  Progression-Free Survival rate at 6 months.

  up to 6 months

Secondary Outcomes (5)

• Progression-Free Survival（PFS）

  up to approximately 24 months

• Objective Response Rate（ORR）

  up to approximately 24 months

• Overall Survival（OS）

  up to approximately 24 months

• Disease Control Rate（DCR）

  up to approximately 24 months

• Safety

  up to approximately 24 months

Study Arms (1)

AK105 injection with anlotinib and radiotherapy

EXPERIMENTAL

AK105 200mg intravenously (IV) on day 1 of each 21-day cycle until disease progression or treatment intolerance, the dose can not be adjusted. Anlotinib 12mg capsules given orally on once daily in 21-day cycle until disease progression or treatment intolerance(14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21), the dose can be adjusted to 10mg or 8mg according to the specific conditions of the patient. The conventional radiotherapy regimen delivered 2.0Gy once a day, five days a week to a total dose of 60Gy.

Drug: Anlotinib; Drug: AK105; Radiation: Radiotherapy

Interventions

Anlotinib DRUG

Anlotinib a multi-target receptor tyrosine kinase inhibitor.

Also known as: Anlotinib Hydrochloride Capsules

AK105 injection with anlotinib and radiotherapy

AK105 DRUG

AK105 is a humanized monoclonal antibody that specifically binds to PD-1.

Also known as: Penpulimab Injection

AK105 injection with anlotinib and radiotherapy

Radiotherapy RADIATION

The radiotherapy regimen delivered 2.0Gy once a day, five days a week to a total dose of 60Gy.

AK105 injection with anlotinib and radiotherapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient voluntarily joined the study and signed a written informed consent;
• Pathologically confirmed treatment-naïve glioblastoma with PCR tested MGMT unmethylated;
• The interval between the last biopsy or surgery is 4-6 weeks, and the surgical incision is healed well;
• According to Rano criteria, there are evaluable measurable disease;
• years of age;
• Karnofsky performance status (KPS) ≥ 60; and estimated survival of at least 3 months;
• The main organ function to meet the following criteria:
• \) routine blood test: HB≥90g/L(no blood transfusion in 14 days); ANC≥1.5×109/L; White blood cell counts≥3.5×109/L; PLT≥90×109/L; 2) blood biochemical test: ALT and AST ≤2.5×ULN(times the upper limit of normal) and if liver/bone metastases≤5×ULN; TBIL ≤1.5 ULN; Serum Cr≤1.5×ULN and CrCL≥60 ml/min; 3) APTT, INR and PT≤1.5×ULN;
• The woman patients of childbearing age who must agree to take contraceptive methods during the research and within another 6 months after it; who are not in the lactation period and examined as negative in blood serum test or urine pregnancy test within 7 days before the research.

You may not qualify if:

• Prior therapy with anti-angiogenic drugs, such as anlotinib, apatinib, lenvatinib, sorafenib, sunitinib, surufatinib, regorafenib or fruquintinib ect, or with anti-PD-1(L1) or anti-CTLA-4 agents;
• Patients who get other monoclonal antibodies have severe hypersensitivity;
• Present or along with other malignancies within 5 years. Exceptions include cured basal cell carcinoma of the skin or in situ prostate cancer or in situ cervical cancer;
• Patients have any active autoimmune disease that required systemic treatment, including but not limited to autoimmune hepatitis, enteritis, vasculitis, nephritis; asthma that require bronchodilators for medical intervention. Exceptions include patients with vitiligo, psoriasis, alopecia or well-controlled type 1 diabetes but not required systemic treatment, or hypothyroidism with normal thyroid function after alternative treatment;
• In the past, there is a treatment toxicity of CTCAE5.0 ≥2 grade that has not been completely relieved (the adverse reaction grades in this article, unless otherwise specified, are defaulted to the CTCAE 5.0 standard);
• Immunodeficiency diagnosis or receiving chronic systemic steroid therapy (\>10mg/day prednisone or equivalent) or any other form of immunosuppressive therapy, and continued to be used within 2 weeks before the first dose in this study;
• Those with multiple factors affecting oral drugs (such as inability to swallow, post gastrointestinal resection, chronic diarrhea and intestinal obstruction, etc.);
• Imaging (CT or MRI) shows that the tumor has invaded or unclearly separated the large blood vessels;
• Patients with active bleeding, or unexplained persistent decline in hemoglobin should postpone their screening/enrollment until the bleeding stops and the investigator judges it to be safe;
• Within 4 weeks before the first dose in this study, patients with CTCAE5.0 grade 3+ bleeding; patients treated with anticoagulants or vitamin K antagonists such as warfarin, heparin or their analogues; on the premise that the international normalized ratio of prothrombin time (INR) ≤1.5, it is allowed to use low-dose warfarin (≤1mg/D), low-dose heparin (≤12000U /D) or low-dose aspirin (≤100mg/D) for preventive purposes;
• Within 4 weeks before the first dose in this study, patients with unhealed wounds, fractures, gastric and duodenal active ulcers, ulcerative colitis, or unresected tumors have active bleeding, or may be caused as determined by the researchers other conditions of gastrointestinal bleeding and perforation, have undergone major surgery (excluding vascular access surgery), inoculated with preventive vaccine or attenuated vaccine;
• Received the treatment of proprietary Chinese medicines with anti-tumor indications specified in the NMPA approved drug instructions within 2 weeks before the start of the study treatment(Including compound cantharidin capsules, Kangai injection, Kanglaite capsule/injection, Aidi injection, brucea javanica oil injection/capsule, Xiaoaiping tablet/injection, Huachansu capsule, etc.); or received drugs with immunomodulatory effects (including thymosin, interferon, and interleukin, except for local use to control pleural effusion or ascites);
• History of organ or blood transplantation;
• Patients have active diverticulitis, abdominal abscess, gastrointestinal obstruction;
• Patients with any severe and/or uncontrollable disease, including:

Sponsors & Collaborators

• The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School: lead
• Chia Tai Tianqing Pharmaceutical Group Co., Ltd.: collaborator

Study Sites (1)

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Nanjing, Jiangsu, 210008, China

RECRUITING

MeSH Terms

Interventions

anlotinib; penpulimab; Radiotherapy

Intervention Hierarchy (Ancestors)

Therapeutics

Central Study Contacts

Mi Yang, Dr.

CONTACT

+86-25-83106666; yangmi@nju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of medicine

Study Record Dates

• First Submitted: August 27, 2021
• First Posted: September 5, 2021
• Study Start: September 1, 2021
• Primary Completion: May 1, 2023
• Study Completion: November 1, 2023
• Last Updated: September 5, 2021

Record last verified: 2021-08

Locations

CN (1)