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

NCT ID: NCT06483347

Last Updated: 2024-07-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-04
• Study Completion Date: 2033-12-30

Brief 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.

Conditions

Lung Cancer; Inoperable Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IT injection of double ICI

Arm 1: intra-tumor injection of double ICIs only.

Group Type: EXPERIMENTAL

ipilimumab+pembrolizumab or ipilimumab+durvalumab, idarubicin, bevacizumab

Intervention Type: DRUG

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.

IT injection of double ICI and chemodrug

Arm 2: intra-tumor injection of double ICIs and a chemodrug.

Group Type: EXPERIMENTAL

ipilimumab+pembrolizumab or ipilimumab+durvalumab, idarubicin, bevacizumab

Intervention Type: DRUG

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.

IT injection of double ICI and chemodrug plus bevacizumab

Arm 3: intra-tumor injection of double ICIs, a chemodrug, and bevacizumab.

Group Type: EXPERIMENTAL

ipilimumab+pembrolizumab or ipilimumab+durvalumab, idarubicin, bevacizumab

Intervention Type: DRUG

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.

Interventions

ipilimumab+pembrolizumab or ipilimumab+durvalumab, idarubicin, bevacizumab

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.

Intervention Type: DRUG

Other Intervention Names

Local ICIs.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Second Affiliated Hospital of Guangzhou Medical University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Zhenfeng Zhang, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Second Affiliated Hospital of Guangzhou Medical University

Locations

Second Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Zhenfeng Zhang, MD, PhD

Role: CONTACT

zhangzhf@gzhmu.edu.cn

+862039195966

Bingjia He, MD

Role: CONTACT

464677938@qq.com

+862039195965

Facility Contacts

Zhang Zhenfeng, MD, PhD

Role: primary

zhangzhf@gzhmu.edu.cn

+862039195966

Other Identifiers

ZZ-IT-ICI-LC 1line-025

Identifier Type: -

Identifier Source: org_study_id