Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05021328
Other study ID # HBCH-RT-2021-01
Secondary ID
Status Recruiting
Phase Phase 1
First received
Last updated
Start date October 1, 2021
Est. completion date June 1, 2025

Study information

Verified date July 2023
Source Hubei Cancer Hospital
Contact Guang Han, MD
Phone 13886048178
Email hg7913@hotmail.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this study is to explore the efficacy and safety of toripalimab combined with anlotinib and SBRT for non-driver gene mutation untreated brain metastases non-small Cell Lung Cancer.


Description:

Brain metastases (BM) develop in 22-54% of NSCLC patients during the disease course. NSCLC patients with BM with a median overall survival (OS) of 2-3 months when treated with systemic corticosteroid alone, and a median OS of 10-12 months when treated with brain radiation therapy. Recently, several studies have reported the benefits of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for EGFR mutation NSCLC patients with BM. The median OS of EGFR mutation patients with BM significantly improved with TKIs treatment, which ranged from 11.8 to 18.8 months. However, for the EGFR wide-type NSCLC patients with BM, the prognosis remains poor. JS-001 is the first monoclonal antibody (mAb) against programmed cell death protein-1 (PD-1) approved by the China Food and Drug Administration (CFDA) into the clinical trails. Anlotinib hydrochloride is a multi-target receptor tyrosine kinase inhibitor that has significant inhibitory activity against angiogenesis related kinases such as VEGFR1/2/3, FGFR1/2/3, and other tumor related kinases such as PDGFR /, C-Kit, Ret, etc. (e.g., Met, FGFR1/2/3). The previously study (2021 EMSO congress abstract) found that Apatinib, another kind of tyrosine kinase inhibitor that selectively inhibits the VEGFR-2, combined with brain radiation therapy could improve mOS time to 17 months in lung cancer patients with BMs. Therefore, the investigators initiated this study to evaluate the efficacy and safety of toripalimab combined with anlotinib and SBRT for non-driver gene mutation untreated brain metastases non-small Cell Lung Cancer.


Recruitment information / eligibility

Status Recruiting
Enrollment 20
Est. completion date June 1, 2025
Est. primary completion date June 1, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: 1. Age = 18 years, no gender limit; 2. Pathologically or cytologically confirmed NSCLC, stage IV tumor with untreated BMs diagnosed by imaging 2 weeks before enrollment, 1~5 intracranial metastases (The primary tumor disease has not received systemic treatment, or brain metastasis occurs 6 months after the completion of postoperative adjuvant treatment or radical treatment); 3. Negative driver genes (EGFR, ALK, ROS1, etc.); 4. ECOG PS score: 0~1; 5. The expected survival time = 3 months; 6. Intracranial metastases can be measured and evaluated by MRI; 7. Intracranial lesions are suitable for stereotactic radiotherapy based on the linear accelerator; 8. Able to independently complete neurocognitive tests; 9. Able to complete the QOL questionnaire independently; 10. Female subjects with fertility should undergo a urine or serum pregnancy test within 72 hours before receiving the first study drug administration, and prove to be negative, and are willing to use effectively during the test period to 3 months after the last administration Methods of contraception. For male subjects whose partners are women of childbearing age, effective methods of contraception should be used during the trial and within 3 months after the last administration; 11. The functions of important organs meet the following requirements (no blood components and cell growth factors are allowed to be used 2 weeks before the start of the research treatment): Absolute Neutrophil Count (ANC) =1.5×10 E+9/L, Hemoglobin (HB) =9g/dL, Platelets (PLT)=90×10 E+9/L, Serum Albumin (ALB)=2.8g/dL, Total Bilirubin (TBIL) =1.5 ULN, ALT?AST=2.5 UILN(If abnormal liver function is caused by liver metastasis, =5 ULN), Serum creatinine sCr=1.5 ULN, endogenous creatinine clearance =50ml/min (Cockcroft-Gault formula) , Normal thyroid function; 12. The patients joined the study voluntarily and signed an informed consent form (ICF). They had good compliance and cooperated with follow-up. Exclusion Criteria: 1. The lesion has received prior radiotherapy and is not suitable for SBRT; 2. Have leptomeningeal metastasis; 3. EGFR, ALK or ROS1 genomic tumour alterations; 4. Patients who cannot undergo MRI examination due to metal implants or claustrophobia; 5. Currently participating in interventional clinical research and treatment, or receiving other research drugs or treatment with research equipment within 4 weeks before the first administration; 6. Accept solid organ or blood system transplantation; 7. Past treatment history of CTLA-4, PD-1 or PD-L1 immune checkpoint inhibitors; 8. Has received VEGF pathway targeted therapy including anlotinib and bevacizumab. 9. Suffer from active autoimmune diseases that require hormone or immunomodulatory treatment, such as rheumatoid arthritis, ankylosing spondylitis, type I diabetes, psoriasis, vitiligo, immune-related thyroid dysfunction, etc. (hormone replacement Can be included after treatment is normal); 10. Suffer from acute or chronic infectious diseases, such as hepatitis B, hepatitis C, tuberculosis, and HIV; 11. Allergic to research drug ingredients 12. Active infection or fever of unknown cause occurred during the screening period and before the first administration> 38.5? (according to the judgment of the investigator, the subject can be included in the group due to fever caused by the tumor); 13. Suffer from uncontrolled clinical symptoms or diseases of the heart, such as:(1) Heart failure above NYHA II; (2) Unstable angina pectoris; (3) Myocardial infarction occurred within 1 year; (4) Patients with clinically significant supraventricular or ventricular arrhythmia requiring clinical intervention; 14. Suffer from high blood pressure and cannot be well controlled by antihypertensive medication (systolic blood pressure =150 mmHg or diastolic blood pressure =100 mmHg); 15. Abnormal blood coagulation function (INR>2.0, PT>16s), have a bleeding tendency or are receiving thrombolytic therapy, and allow preventive use of low-dose aspirin and low-molecular-weight heparin; 16. Obvious coughing up blood or hemoptysis of 10ml or more per day in the 2 months before enrollment; 17. Have significant clinically significant bleeding symptoms or have a clear bleeding tendency within 3 months before enrollment; 18. Have received anti-tumor monoclonal antibodies (mAb) within 4 weeks before using the study drug for the first time, or the adverse events caused by the previously received drug have not recovered (ie = grade 1 or reached the baseline level). Note: Except for subjects with = Grade 2 neuropathy or = Grade 2 hair loss, if the subject has undergone major surgery, the toxic reaction and/or complications caused by the surgical intervention must be fully recovered before starting treatment; 19. Live vaccines have been vaccinated within 4 weeks before the first use of the study drug. Inactivated virus vaccines for seasonal influenza and injections are allowed, but live attenuated influenza vaccines for nasal use are not allowed; 20. The investigator judged other situations not suitable for inclusion in this study.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Toripalimab
Toripalimab 240mg, ivgtt, d1, q3w.
Anlotinib
Anlotinib 12 mg/d, d1-14, q3w.
SBRT 7Gy??5 QD
SBRT 7Gy??5 QD

Locations

Country Name City State
China Hubei Cancer Hospital Wuhan Hubei

Sponsors (1)

Lead Sponsor Collaborator
Hubei Cancer Hospital

Country where clinical trial is conducted

China, 

Outcome

Type Measure Description Time frame Safety issue
Primary Treatment-related adverse events AEs per Common Terminology Criteria for Adverse Events (CTCAE V5.0) up to 24 month
Primary Intracranial response rate (iORR) Proportion of patients with a complete or partial response in intracranial metastases as measured using RECIST 1.1 criteria (modified for brain metastases - bm RECIST). 4 weeks after Radiotherapy.
Secondary Intracranial progression-free survival (iPFS) Defined as the time from randomisation to progression of intracranial disease or death from any cause. Tumor assesment at 4 weeks and 12 weeks after radiotherapy, and then every 12 weeks, up to 24 months
Secondary Local Control Rate (LCR) Local recurrence is defined as the onset or progression of nodular contrast grafting within the resection cavity according to the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria. Tumor assesment at 4 weeks and 12 weeks after radiotherapy, and then every 12 weeks, up to 24 months
Secondary Overall survival (OS) Defined as the time from randomisation to death from any cause Tumor assesment at 4 weeks and 12 weeks after radiotherapy, and then every 12 weeks, up to 24 months
See also
  Status Clinical Trial Phase
Recruiting NCT05821933 - RC108 Combine With Furmonertinib With/Without Toripalimab in Patients With EGFR-mutated NSCLC Phase 1/Phase 2
Active, not recruiting NCT03269162 - Postoperative NSCLC Treated With Integrated Medicine Base on Circulating Tumor Cell Detection Phase 3
Recruiting NCT05002270 - JAB-21822 Activity in Adult Patients With Advanced Solid Tumors Harboring KRAS G12C Mutation Phase 1/Phase 2
Recruiting NCT06315686 - The Dynamic Monitoring of Cerebrospinal Fluid ctDNA Phase 2
Active, not recruiting NCT05059522 - Continued Access Study for Participants Deriving Benefit in Pfizer-Sponsored Avelumab Parent Studies That Are Closing Phase 3
Recruiting NCT05466149 - Efficacy and Safety of Furmonertinib in Patients With Locally Advanced or Metastatic NSCLC With EGFR Exon 20 Insertion Phase 2
Recruiting NCT03175224 - APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors Phase 2
Completed NCT03609918 - Comprehensive Analysis of Gene Mutation Profile in Chinese NSCLC Patients by Next-generation Sequencing
Recruiting NCT06043817 - First-In-Human Study of STX-721 in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Harboring EGFR Exon 20 Insertion Mutations Phase 1/Phase 2
Completed NCT03652077 - A Safety and Tolerability Study of INCAGN02390 in Select Advanced Malignancies Phase 1
Recruiting NCT05078931 - A Study to Evaluate Pembrolizumab Plus Lenvatinib in PD-L1 Positive TKI Resistant NSCLC Patients Phase 2
Not yet recruiting NCT05547737 - Multicenter, Prospective, Real World Study of Camrelizumab in Cross-line Treatment of Non-small Cell Lung Cancer
Not yet recruiting NCT05909137 - Omitting Clinical Target Volume in Radical Treatment of Unresectable Stage III Non-small Cell Lung Cancer
Withdrawn NCT05959473 - EGFR_IUO 3.20 Clinical Study Protocol N/A
Not yet recruiting NCT05005468 - A Phase II Trial of Camrelizumab Combined With Famitinib for Adjuvant Treatment of Stage II-IIIA NSCLC. Phase 2
Recruiting NCT01690390 - Dose Escalation of Icotinib in Advanced Non-small Cell Lung Carcinoma (NSCLC) Patients Evaluated as Stable Disease Phase 2
Completed NCT01852578 - Cabazitaxel in Relapsed and Metastatic NSCLC Phase 2
Active, not recruiting NCT01460472 - Immunotherapy With Racotumomab in Advanced Lung Cancer Phase 3
Completed NCT00702975 - Study of Combination Therapy of Carboplatin -Gemcitabine Plus Bevacizumab Beyond Progression in Patients With Locally Advanced and/or Metastatic Non-small Cell Lung Cancer (NSCLC) Who Have Not Received Prior Systemic Therapy Phase 2
Completed NCT00866970 - Safety, Efficacy and Pharmacokinetics of ALD518 in Patients With Non-Small Cell Lung Cancer-related Fatigue and Cachexia Phase 2