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Triplex Checkpoint Inhibitors Therapy for Advanced Solid Tumors

Primary Purpose

Lung Cancer, Liver Cancer, Colorectal Cancer

Status

Recruiting

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

ipilimumab +pembrolizumab +durvalumab

About this trial

This is an interventional treatment trial for Lung Cancer focused on measuring Solid tumor, CTLA4 antibody, PD1 antibody, PDL1 antibody, Interventional Radiology, Trans-artery infusion, Intra-tumor injection

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Cytohistological confirmation is required for diagnosis of cancer.
Signed informed consent before recruiting.
Age above 18 years with estimated survival over 3 months.
Child-Pugh class A or B/Child score > 7; ECOG score < 2
Tolerable coagulation function or reversible coagulation disorders
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
At least one tumor lesion meeting measurable disease criteria as determined by RECIST v1.1.
Birth control.
Willing and able to comply with scheduled visits, treatment plan and laboratory tests.

Exclusion Criteria:

Patients participated in clinical trials of equipment or drugs (signed informed consent) within 4 weeks;
Patients accompany by ascites, hepatic encephalopathy and esophageal and gastric varices bleeding;
Any serious accompanying disease, which is expected to have an unknown, impact on the prognosis, include heart disease, inadequately controlled diabetes and psychiatric disorders;
Patients accompanied with other tumors or past medical history of malignancy;
Pregnant or lactating patients, all patients participating in this trial must adopt appropriate birth control measures during treatment;
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).
Allergic to contrast agent;
Any agents which could affect the absorption or pharmacokinetics of the study drugs
Other conditions that investigator decides not suitable for the trial.

Sites / Locations

The Second Affiliated Hospital of Guangzhou Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

3 drugs

Arm Description

Three antibodies combination against PD1, PDL1, and CTLA4.

Outcomes

Primary Outcome Measures

Safety of 3 drugs combination treatment

Safety will be assessed by recording all types of advise effects upon and after the treatment.

Progression-free survival

Progression-free survival (PFS) will be defined as the elapsed time from the first date of study treatment until documented disease progression (as per RECIST 1.1) or death from any cause, whichever is earlier. For patients who remain alive without progression, follow-up time will be censored at the date of last disease assessment.

Disease control rate

Disease control rate will be defined as objective response rate + steady disease rate.

Duration of remission (DOR)

DOR will be defined as the duration of the cancer remission

Secondary Outcome Measures

Overall survival

Overall survival (OS) will be defined as the elapsed time from the enrollment to death from any cause. For surviving patients, follow-up will be censored at the date of last contact (or last date known to be alive). Follow-up for OS will occur every 12 weeks (±1 month) until death or withdrawal of consent from the study.

Full Information

NCT ID

NCT05187338

First Posted

December 28, 2021

Last Updated

February 11, 2023

Sponsor

Second Affiliated Hospital of Guangzhou Medical University

1. Study Identification

Unique Protocol Identification Number

NCT05187338

Brief Title

Triplex Checkpoint Inhibitors Therapy for Advanced Solid Tumors

Official Title

Triplex CTLA4/PD1/PDL1 Checkpoint Inhibitors Combination Therapy for Advanced Solid Tumors

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Recruiting

Study Start Date

November 1, 2021 (Actual)

Primary Completion Date

October 30, 2024 (Anticipated)

Study Completion Date

October 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Second Affiliated Hospital of Guangzhou Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

5. Study Description

Brief Summary

This trial is designed to investigate the safety, response rates and survival outcomes of patients with advanced solid tumors by infusion of CTLA4, PD1 and PDL1 antibodies combination through venous (IV), artery (IA) or intra-tumor (IT).

Detailed Description

Malignant solid tumors including lung and liver cancers are the most common malignancy worldwide, and their mortality rates are very high. China has a huge population base with about 4,000,000 new cancer cases each year. More than 60% of the solid tumors in China are diagnosed at mid-to-late stage and have lost the chance of surgery. Recently a lot of therapeutic strategies have been developed and applied to clinic including targeted therapy and immunotherapy, but the overall therapeutic efficiency is still low. It is very difficult to treat patients with recurrent/refractory/metastatic advanced solid cancers and more alternative therapies are urgently needed. 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, PD1 antibody and PDL1 antibody, so called triplex checkpoint inhibitors combination therapy, for advanced solid tumors. To the investigator's knowledge, no studies have been developed on the safety, efficacy and survival benefit of the triplex checkpoint inhibitors combination therapy for cancer patients. This phase I-II clinical trial is designed to assess the safety and survival benefit of ipilimumab, pembrolizumab and durvalumab combination on patients with advanced solid cancers, including PFS, ORR, DCR, and median survival time.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lung Cancer, Liver Cancer, Colorectal Cancer, Pancreas Cancer, Ovary Cancer, Head and Neck Cancer, Breast Cancer, Gastric Cancer, Cervical Cancer, Esophageal Cancer, Sarcoma

Keywords

Solid tumor, CTLA4 antibody, PD1 antibody, PDL1 antibody, Interventional Radiology, Trans-artery infusion, Intra-tumor injection

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

3 drugs

Arm Type

Experimental

Arm Description

Three antibodies combination against PD1, PDL1, and CTLA4.

Intervention Type

Drug

Intervention Name(s)

ipilimumab +pembrolizumab +durvalumab

Intervention Description

This study has 3 subgroups: Ipilimumab +pembrolizumab +durvalumab is administrated with a total dose of 1-2mg/kg via vein, every 3 weeks. Ipilimumab +pembrolizumab +durvalumab is administrated with a total dose of 1-2mg/kg via sustained (10min) micro-pump infusion via artery, every 3 weeks. Ipilimumab +pembrolizumab +durvalumab is administrated with a total dose of 50-150mg via intra-tumor fine needle injection in 5 min, every 3 weeks.

Primary Outcome Measure Information:

Title

Safety of 3 drugs combination treatment

Description

Safety will be assessed by recording all types of advise effects upon and after the treatment.

Time Frame

5 years

Title

Progression-free survival

Description

Time Frame

5 years

Title

Disease control rate

Description

Disease control rate will be defined as objective response rate + steady disease rate.

Time Frame

5 years

Title

Duration of remission (DOR)

Description

DOR will be defined as the duration of the cancer remission

Time Frame

5 years

Secondary Outcome Measure Information:

Title

Overall survival

Description

Time Frame

5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Cytohistological confirmation is required for diagnosis of cancer. Signed informed consent before recruiting. Age above 18 years with estimated survival over 3 months. Child-Pugh class A or B/Child score > 7; ECOG score < 2 Tolerable coagulation function or reversible coagulation disorders 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 At least one tumor lesion meeting measurable disease criteria as determined by RECIST v1.1. Birth control. Willing and able to comply with scheduled visits, treatment plan and laboratory tests. Exclusion Criteria: Patients participated in clinical trials of equipment or drugs (signed informed consent) within 4 weeks; Patients accompany by ascites, hepatic encephalopathy and esophageal and gastric varices bleeding; Any serious accompanying disease, which is expected to have an unknown, impact on the prognosis, include heart disease, inadequately controlled diabetes and psychiatric disorders; Patients accompanied with other tumors or past medical history of malignancy; Pregnant or lactating patients, all patients participating in this trial must adopt appropriate birth control measures during treatment; 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). Allergic to contrast agent; Any agents which could affect the absorption or pharmacokinetics of the study drugs Other conditions that investigator decides not suitable for the trial.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Zhenfeng Zhang, MD, PHD

Phone

+862039195966

zhangzhf@gzhmu.edu.cn

First Name & Middle Initial & Last Name or Official Title & Degree

Bingjia He, MD

Phone

+862039195965

464677938@qq.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Zhenfeng Zhang, MD, PHD

Organizational Affiliation

Second Affiliated Hospital of Guangzhou Medical University

Official's Role

Principal Investigator

Facility Information:

Facility Name

The Second Affiliated Hospital of Guangzhou Medical University

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510260

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Zhenfeng Zhang, MD, PHD

First Name & Middle Initial & Last Name & Degree

Bingjia He, MD

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Triplex Checkpoint Inhibitors Therapy for Advanced Solid Tumors

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