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Trans-Artery/Intra-Tumor Infusion of Checkpoint Inhibitors Plus Chemodrug for Immunotherapy of Advanced Solid Tumors

Primary Purpose

Hepatocarcinoma, Lung Cancer, Melanoma

Status

Recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Checkpoint inhibitor (CPI) such as Pembrolizumab plus chemotherapy

About this trial

This is an interventional treatment trial for Hepatocarcinoma focused on measuring Solid cancers, Check-point inhibitors, Interventional Radiology, Trans-artery infusion, Intra-tumor injection

Eligibility Criteria

18 Years - undefined (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 2

Arm Type

Experimental

Active Comparator

Arm Label

Pembrolizumab via localized infusion

Checkpoint inhibitor (CPI) Pembrolizumab plus chemotherapy via vein infusion

Arm Description

This group dividied into two subgroups: Checkpoint inhibitor (CPI) such as Pembrolizumab ± Ipilimumab is administrated with a dose of 1-2mg/kg via sustained (10min) micro-pump infusion via artery, plus chemotherapy, every 3 weeks. Checkpoint inhibitor (CPI) such as Pembrolizumab ± Ipilimumab is administrated with a total dose of 150mg via intra-tumor fine needle injection in 5 min, plus doxorubicin, every 3 weeks.

Checkpoint inhibitor (CPI) such as Pembrolizumab is administrated with a total dose of 2mg/kg via vein infusion (30 min), plus chemotherpy every 3 weeks.

Outcomes

Primary 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.

Complete response (CR) rate before or at Month 6

Percentage of patients achieving complete response (CR) before or at Month 6

Secondary Outcome Measures

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 mRECIST) 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.

Duration of remission (DOR)

DOR will be defined as the duration of the cancer remission

Disease control rate

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

Cause of death (COD) when appropriate

Full Information

NCT ID

NCT03755739

First Posted

November 3, 2018

Last Updated

February 26, 2023

Sponsor

Second Affiliated Hospital of Guangzhou Medical University

1. Study Identification

Unique Protocol Identification Number

NCT03755739

Brief Title

Trans-Artery/Intra-Tumor Infusion of Checkpoint Inhibitors Plus Chemodrug for Immunotherapy of Advanced Solid Tumors

Official Title

A Phase II/III Trial of Comparison of Benefit of Administration of Checkpoint Inhibitors Plus Chemodrug Via Artery or Fine Needle to Tumor Versus Vein for Immunotherapy of Advanced Solid Tumors

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Recruiting

Study Start Date

November 1, 2018 (Actual)

Primary Completion Date

November 1, 2033 (Anticipated)

Study Completion Date

November 1, 2033 (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

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This trial was designed to investigate the safety, response rates and survival outcomes of patients with advanced solid tumors by trans-artery/intra-tumor infusion of PD1/PDL1 antibody and/or CTLA4 antibody ipilimumab plus chemotherapeutic drug and to compare their differences.

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 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 efficiency is still low. It is difficult to be widely used in patients with advanced solid cancers, and more alternative therapies are urgently needed. Antibodies against PD1, PDL1 and CTLA4 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 in the tumor, improve the efficacy, and reduce systemic adverse reactions, through so called "first pass effect" of drug on target organs. To the investigator's knowledge, no studies have been developed on the efficacy and survival benefit of localized delivery of checkpoint inhibitors for treatment of cancer patients. This phase II-III clinical trial was designed to compare the effects of Pembrolizumab, Tecentriq, et al and/or ipilimumab plus chemotherapeutic drug such as doxorubicin on the survival benefit of patients with advanced solid cancers, including ORR, DCR, median survival time, and safety.

6. Conditions and Keywords

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

Hepatocarcinoma, Lung Cancer, Melanoma, Renal Cancer, Head and Neck Cancer, Pancreas Cancer, Ovarian Cancer, Colo-rectal Cancer, Cervical Cancer, Breast Cancer

Keywords

Solid cancers, Check-point inhibitors, Interventional Radiology, Trans-artery infusion, Intra-tumor injection

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Pembrolizumab via localized infusion

Arm Type

Experimental

Arm Description

Arm Title

Checkpoint inhibitor (CPI) Pembrolizumab plus chemotherapy via vein infusion

Arm Type

Active Comparator

Arm Description

Checkpoint inhibitor (CPI) such as Pembrolizumab is administrated with a total dose of 2mg/kg via vein infusion (30 min), plus chemotherpy every 3 weeks.

Intervention Type

Drug

Intervention Name(s)

Checkpoint inhibitor (CPI) such as Pembrolizumab plus chemotherapy

Other Intervention Name(s)

Checkpoint inhibitor (CPI) such as Keytruda plus chemotherapy

Intervention Description

vein, artery, or intra-tumor infusion of checkpoint inhibitor (CPI) such as Pembrolizumab and/or Ipilimumab, plus chemotherapy to destroy cancer cells and release tumor antigen for improving CPI therapeutic efficacy.

Primary Outcome Measure Information:

Title

Overall survival

Description

Time Frame

5 years

Title

Complete response (CR) rate before or at Month 6

Description

Percentage of patients achieving complete response (CR) before or at Month 6

Time Frame

Secondary Outcome Measure Information:

Title

Progression-free survival

Description

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

Title

Disease control rate

Description

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

Time Frame

5 years

Title

Cause of death (COD) when appropriate

Description

Cause of death (COD) when appropriate

Time Frame

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 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

02034153532

zhangzhf@gzhmu.edu.cn

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

Deji Chen, MD,PhD

Phone

02034153532

chendeji2003@163.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

Guanzhou

State/Province

Guangdong

ZIP/Postal Code

51260

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Zhenfeng Zhang, MD,PhD

Phone

02034153532

zhangzhf@gzhmu.edu.cn

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Trans-Artery/Intra-Tumor Infusion of Checkpoint Inhibitors Plus Chemodrug for Immunotherapy of Advanced Solid Tumors

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