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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
Sponsored by
Second Affiliated Hospital of Guangzhou Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

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:

  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.

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
Cause of death (COD) when appropriate

Full Information

First Posted
November 3, 2018
Last Updated
February 26, 2023
Sponsor
Second Affiliated Hospital of Guangzhou Medical University
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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
No
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
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.
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
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.
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
4
Secondary Outcome Measure Information:
Title
Progression-free survival
Description
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.
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
5

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Email
zhangzhf@gzhmu.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Deji Chen, MD,PhD
Phone
02034153532
Email
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
Email
zhangzhf@gzhmu.edu.cn

12. IPD Sharing Statement

Plan to Share IPD
No

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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