Checkpoint Inhibitor Combinations Therapy as First Line for Inoperable Lung Cancer Via IT

Trial Title: Checkpoint Inhibitor Combinations Therapy as First Line for Inoperable Lung Cancer Via IT

NCT ID: NCT06483347

Condition: Lung Cancer
Inoperable Disease

Conditions: Official terms:
Lung Neoplasms
Bevacizumab
Pembrolizumab
Ipilimumab
Durvalumab
Idarubicin

Conditions: Keywords:
Inoperable lung cancer
Intra-tumor injection
Immunotherapy
First line therapy

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: ipilimumab+pembrolizumab or ipilimumab+durvalumab, idarubicin, bevacizumab
Description: This study has 3 subgroups: Arm 1. Ipilimumab +pembrolizumab or Ipilimumab +durvalumab is administrated with a total dose of 1-2mg/kg via intra-tumor fine needle injection in 10 min, every 3 weeks. Arm 2. Ipilimumab +pembrolizumab or Ipilimumab +durvalumab combined with idarubicin is administrated via intra-tumor fine needle injection in 15 min, every 3 weeks. Arm 3. Ipilimumab +pembrolizumab or Ipilimumab +durvalumab combined with idarubicin plus bevacizumab is administrated via intra-tumor fine needle injection in 20 min, every 3 weeks.
Arm group label: IT injection of double ICI
Arm group label: IT injection of double ICI and chemodrug
Arm group label: IT injection of double ICI and chemodrug plus bevacizumab

Other name: Local ICIs.

Summary: This trial is designed to investigate the safety, response rates and survival outcomes of patients with inoperable lung cancer by infusion of CTLA4, PD1 and PDL1 antibodies combination with chemodrug or/and bevacizumab through intra-tumor (IT).

Detailed description: Antibodies against CTLA4, PD1 and PDL1 are representative drugs for the check-points inhibitory agents, and their clinical indications have been approved in various types of tumors, including advanced melanoma, non-small cell lung cancer, renal cell carcinoma, and classical Hodgkin's lymphoma and late recurrent head and neck squamous cell carcinoma patients, et al. Those drugs are regularly systemically administrated by vein infusion, however, local delivery of those drugs via interventional radiology technique including trans-artery or intra-tumor injection may increase the local drug concentration of the tumor, improve the efficacy, and reduce systemic adverse reactions. CTLA4 antibody ipilimumab has been widely effectively using to combine with PD1 or PDL1 antibody and this study is to combine ipilimumab and PD1 antibody or PDL1 antibody, so called double checkpoint inhibitors combination therapy, as first line for inoperable lung cancer via intra-tumor admistration. To the investigator's knowledge, no studies have been developed on the safety, efficacy and survival benefit of the double checkpoint inhibitors combination therapy for cancer patients as first line via intra-tumor delivery. This phase II clinical trial is designed to assess the safety and survival benefit of ipilimumab and pembrolizumab or durvalumab combination with or without chemodrug or bevacizumab as first line therapy on patients with inoperable lung cancer, including PFS, ORR, DCR, and median survival time.

Criteria for eligibility:
Criteria:
Inclusion Criteria: 1. Cytohistological confirmation is required for diagnosis of cancer. 2. Signed informed consent before recruiting. 3. Age above 18 years with estimated survival over 3 months. 4. Child-Pugh class A or B/Child score > 7; ECOG score < 2 5. Tolerable coagulation function or reversible coagulation disorders 6. Laboratory examination test within 7 days prior to procedure: WBC≥3.0×10E9/L; Hb≥90g/L； PLT ≥50×10E9/L；INR < 2.3 or PT < 6 seconds above control；Cr ≤ 145.5 umul/L；Albumin > 28 g/L；Total bilirubin < 51 μmol/L 7. At least one tumor lesion meeting measurable disease criteria as determined by RECIST v1.1. 8. Birth control. 9. Willing and able to comply with scheduled visits, treatment plan and laboratory tests. Exclusion Criteria: 1. Patients participated in clinical trials of equipment or drugs (signed informed consent) within 4 weeks; 2. Patients accompany by ascites, hepatic encephalopathy and esophageal and gastric varices bleeding; 3. Any serious accompanying disease, which is expected to have an unknown, impact on the prognosis, include heart disease, inadequately controlled diabetes and psychiatric disorders; 4. Patients accompanied with other tumors or past medical history of malignancy; 5. Pregnant or lactating patients, all patients participating in this trial must adopt appropriate birth control measures during treatment; 6. Patients have poor compliance. Any contraindications for hepatic arterial infusion procedure: A.Impaired clotting test (platelet count < 60000/mm3, prothrombin activity < 50%). B.Renal failure / insufficiency requiring hemo-or peritoneal dialysis. C.Known severe atheromatosis. D.Known uncontrolled blood hypertension (> 160/100 mm/Hg). 7. Allergic to contrast agent; 8. Any agents which could affect the absorption or pharmacokinetics of the study drugs 9. Other conditions that investigator decides not suitable for the trial.

Gender: All

Minimum age: 18 Years

Maximum age: 75 Years

Healthy volunteers: No

Locations:

Facility:
Name: Second Affiliated Hospital of Guangzhou Medical University

Address:
City: Guangzhou
Country: China

Status: Recruiting

Contact:
Last name: Zhang Zhenfeng, MD, PhD

Phone: +862039195966
Email: zhangzhf@gzhmu.edu.cn

Start date: April 4, 2024

Completion date: December 30, 2033

Lead sponsor:
Agency: Second Affiliated Hospital of Guangzhou Medical University
Agency class: Other

Source: Second Affiliated Hospital of Guangzhou Medical University

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06483347