search
Back to results

A Phase Ib/II Clinical Study of Camrelizumab and Apatinib Plus GP in the Treatment of Advanced Biliary Tract Cancer

Primary Purpose

Locally Advanced Biliary Tract Cancer, Metastatic Biliary Tract Cancer

Status
Not yet recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Camrelizumab and Apatinib Plus GP
Sponsored by
Sun Yat-sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Locally Advanced Biliary Tract Cancer focused on measuring Biliary Tract Cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Subject must be able to comprehend and willing to sign an informed consent form (ICF). Subject must have a pathologically or cytologically confirmed carcinoma (except neuroendocrine) of the biliary tract (intra-hepatic, extra-hepatic (hilar, distal) or gallbladder) that is not eligible for curative resection, transplantation, or ablative therapies. Tumors of mixed cholangiocarcinoma/hepatocellular carcinoma histology are excluded. Subject must be 18-75 years of age at the time of signature of the ICF. Subject must have an ECOG performance status of 0-1. Estimated life expectancy no less than 3 months. Subject may not have received prior systemic treatment (chemotherapy or targeted therapy) for advanced BTC. Prior peri-operative chemotherapy is permitted provided it was completed > 6 months from enrollment. Subject must have a lesion that can be accurately assessed at baseline by CT or magnetic resonance imaging (MRI) and is suitable for repeated assessment in accordance with RECIST v1.1. Subject must have normal organ and marrow function as defined below within 14 days of study entry: Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L, platelets ≥ 75 × 10^9/L, or hemoglobin ≥ 9 g/dL. International normalized ratio (INR) < 1.5 or a prothrombin time (PT)/partial thromboplastin time (PTT) within normal limits. Patients receiving anticoagulation treatment with an agent such as warfarin will not be candidates for the trial. Patients on anticoagulation with low molecular weight or heparinoids are protocol candidates. Total bilirubin ≤ 1.5 × upper limit of normal (ULN) unless liver metastasis or BTC in which case ≤ 5 × ULN is permitted at the investigator's discretion. Aspartate transaminase (AST) and Alanine transaminase (ALT) ≤ 3 × ULN. Creatinine ≤ 1.5 × ULN, or creatinine clearance ≥ 50 mL/min (measured or calculated by Cockcroft and Gault equation). Baseline left ventricular ejection fraction (LVEF) ≥ 60% measured by echocardiography or Multiple Gated Acquisition Scan (MUGA) Exclusion Criteria: Patients with any of the following were excluded from the study: Any investigational agents or study drugs from a previous clinical study within 4 weeks of the first dose of study treatment. Malignancies other than BTC within 5 years prior to study enrollment, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated with curative intent, or breast ductal carcinoma in situ treated surgically with curative intent). Prior history of brain metastasis (unless previously treated, asymptomatic and stable for at least 3 months) or organ transplant. Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study treatment. Active bleeding during the last 4 weeks prior to screening or in the investigator's judgment, the existence of high bleeding tendency lesions such as active gastrointestinal ulcers or prominent esophageal or gastric varices. Significant cardiovascular disease, including: Heart disease classified as New York Heart Association class III or IV. Ongoing uncontrolled hypertension. History of congenital long QT syndrome. Ongoing prolonged QT interval corrected for heart rate using Fridericia's method (QTcF) defined as ≥ 470 msec. History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation). Subjects with atrial fibrillation, that is well controlled with treatment, can be enrolled. Active heart disease including symptomatic heart failure (NYHA class 3 or 4), unstable angina pectoris, uncontrolled cardiac arrhythmia or interstitial lung disease. Prolonged QTcF interval >480 msec. Ongoing active, uncontrolled infection (must be afebrile for > 48 hours off antibiotics). With the exception of alopecia, any unresolved toxicities from prior therapy ≥Common Terminology Criteria for Adverse Events (CTCAE) Grade 2. Pregnancy or breastfeeding. (Women must not be pregnant or breastfeeding since study drugs may harm the fetus or child. All females of childbearing potential [not surgically sterilized and between menarche and 1 year post menopause] must have a negative screening pregnancy test.) History of human immunodeficiency virus infection. History of autoimmune disease. Ascertained hypersensitivity to gemcitabine, cisplatin, camrelizumab or apatinib, or drugs with similar chemical structures, or its inactive components. If there is suspicion that the subject may have an allergy, the subject should be excluded. Psychiatric illness, other significant medical illness, or social situation which, in the investigator's opinion, would limit compliance or ability to comply with study requirements. Judgment by the investigators that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.

Sites / Locations

  • Cancer center of SunYat-sen University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Camrelizumab + apatinib and chemotherapies (gemcitabine and cisplatin)

Arm Description

Apatinib is a multi-target TKI, which selectively inhibits VEGFR-2. Camrelizumabb is a anti-human PD-1 monoclonal antibody.

Outcomes

Primary Outcome Measures

Incidence of dose-limiting toxicity
Dose limiting toxicities will determine the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) of combination therapy with camrelizumab + apatinib and gemcitabine plus cisplatin. Assessed using the NCI CTCAE v5.0
Recommended phase 2 dose(RP2D) of apatinib
To determine a RP2D of apatinib for each population of biliary tract carcinoma subjects.
Objective Response Rate (ORR)
Defined as percentage of participants achieving assessed complete response (CR) and partial response (PR) by the investigator according to the RECIST 1.1.

Secondary Outcome Measures

Adverse Events (AE)
overall incidence of adverse events (AE); incidence of grade 3 or higher AE; incidence of severe adverse events (SAE); incidence of AEs leading to discontinuation of drug use; incidence of AEs leading to suspension of drug use.
Disease Control Rate (DCR)
DCR was defined as the percentage of participants who have a confirmed complete response(CR) or partial response(PR) or stable disease(SD) per RECIST 1.1 as assessed by investigator
Progression-Free Survival (PFS)
PFS is defined as the time from enrollment to the first documented disease progression or death due to any cause, whichever occurs first. Responses are according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by investigator
Overall Survival (OS)
OS is the time from enrollment to death due to any cause.

Full Information

First Posted
February 15, 2023
Last Updated
February 15, 2023
Sponsor
Sun Yat-sen University
Collaborators
Jiangsu Hengrui Pharmaceutical Co., Ltd.
search

1. Study Identification

Unique Protocol Identification Number
NCT05742750
Brief Title
A Phase Ib/II Clinical Study of Camrelizumab and Apatinib Plus GP in the Treatment of Advanced Biliary Tract Cancer
Official Title
Camrelizumab Combined With Apatinib and Gemcitabine Plus Cisplatin as First-line Therapy for Patients With Inoperable/Metastatic Biliary Tract Cancer (BTC): An Open-label, Single-arm, Single-center, Phase Ib/II Clinical Study
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
March 1, 2023 (Anticipated)
Primary Completion Date
December 30, 2023 (Anticipated)
Study Completion Date
December 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University
Collaborators
Jiangsu Hengrui Pharmaceutical Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The objective of this study is to investigate the safety and tolerability of camrelizumab combined with apatinib and chemotherapies (gemcitabine and cisplatin) in patients with advanced biliary tract cancer (BTC).
Detailed Description
The study consists of 2 parts, a dose-escalation part (Phase 1) and an expansion part (Phase 2). Both parts will enroll participants with advanced unresectable biliary tract cancer that had not previously treated with systemic therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Locally Advanced Biliary Tract Cancer, Metastatic Biliary Tract Cancer
Keywords
Biliary Tract Cancer

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
48 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Camrelizumab + apatinib and chemotherapies (gemcitabine and cisplatin)
Arm Type
Experimental
Arm Description
Apatinib is a multi-target TKI, which selectively inhibits VEGFR-2. Camrelizumabb is a anti-human PD-1 monoclonal antibody.
Intervention Type
Drug
Intervention Name(s)
Camrelizumab and Apatinib Plus GP
Other Intervention Name(s)
Apatinib (Apatinib Mesylate Tablets, Jiangsu Hengrui Medicine, China), Camrelizumab (Carelizumab for Injection, Jiangsu Hengrui Medicine, China)
Intervention Description
Patients received apatinib orally at 250 mg once a day irrespective of the patient weight. Camrelizumab 200 mg was administered intravenously over 30 minutes every 3 weeks. GP chemotherapy: Gemcitabine/Cisplatin (gemcitabine 1000mg/m2 + cisplatin 25mg/m2) will be administered on D1/D8 in every three weeks cycle and up to 8 cycles. All patients continued combination treatment until disease progression, unacceptable toxicity, or discontinuation for any reason.
Primary Outcome Measure Information:
Title
Incidence of dose-limiting toxicity
Description
Dose limiting toxicities will determine the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) of combination therapy with camrelizumab + apatinib and gemcitabine plus cisplatin. Assessed using the NCI CTCAE v5.0
Time Frame
up to day 22
Title
Recommended phase 2 dose(RP2D) of apatinib
Description
To determine a RP2D of apatinib for each population of biliary tract carcinoma subjects.
Time Frame
12 weeks
Title
Objective Response Rate (ORR)
Description
Defined as percentage of participants achieving assessed complete response (CR) and partial response (PR) by the investigator according to the RECIST 1.1.
Time Frame
up to 24 months
Secondary Outcome Measure Information:
Title
Adverse Events (AE)
Description
overall incidence of adverse events (AE); incidence of grade 3 or higher AE; incidence of severe adverse events (SAE); incidence of AEs leading to discontinuation of drug use; incidence of AEs leading to suspension of drug use.
Time Frame
up to 24 months
Title
Disease Control Rate (DCR)
Description
DCR was defined as the percentage of participants who have a confirmed complete response(CR) or partial response(PR) or stable disease(SD) per RECIST 1.1 as assessed by investigator
Time Frame
up to 24 months
Title
Progression-Free Survival (PFS)
Description
PFS is defined as the time from enrollment to the first documented disease progression or death due to any cause, whichever occurs first. Responses are according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by investigator
Time Frame
up to 24 months
Title
Overall Survival (OS)
Description
OS is the time from enrollment to death due to any cause.
Time Frame
up to 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subject must be able to comprehend and willing to sign an informed consent form (ICF). Subject must have a pathologically or cytologically confirmed carcinoma (except neuroendocrine) of the biliary tract (intra-hepatic, extra-hepatic (hilar, distal) or gallbladder) that is not eligible for curative resection, transplantation, or ablative therapies. Tumors of mixed cholangiocarcinoma/hepatocellular carcinoma histology are excluded. Subject must be 18-75 years of age at the time of signature of the ICF. Subject must have an ECOG performance status of 0-1. Estimated life expectancy no less than 3 months. Subject may not have received prior systemic treatment (chemotherapy or targeted therapy) for advanced BTC. Prior peri-operative chemotherapy is permitted provided it was completed > 6 months from enrollment. Subject must have a lesion that can be accurately assessed at baseline by CT or magnetic resonance imaging (MRI) and is suitable for repeated assessment in accordance with RECIST v1.1. Subject must have normal organ and marrow function as defined below within 14 days of study entry: Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L, platelets ≥ 75 × 10^9/L, or hemoglobin ≥ 9 g/dL. International normalized ratio (INR) < 1.5 or a prothrombin time (PT)/partial thromboplastin time (PTT) within normal limits. Patients receiving anticoagulation treatment with an agent such as warfarin will not be candidates for the trial. Patients on anticoagulation with low molecular weight or heparinoids are protocol candidates. Total bilirubin ≤ 1.5 × upper limit of normal (ULN) unless liver metastasis or BTC in which case ≤ 5 × ULN is permitted at the investigator's discretion. Aspartate transaminase (AST) and Alanine transaminase (ALT) ≤ 3 × ULN. Creatinine ≤ 1.5 × ULN, or creatinine clearance ≥ 50 mL/min (measured or calculated by Cockcroft and Gault equation). Baseline left ventricular ejection fraction (LVEF) ≥ 60% measured by echocardiography or Multiple Gated Acquisition Scan (MUGA) Exclusion Criteria: Patients with any of the following were excluded from the study: Any investigational agents or study drugs from a previous clinical study within 4 weeks of the first dose of study treatment. Malignancies other than BTC within 5 years prior to study enrollment, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated with curative intent, or breast ductal carcinoma in situ treated surgically with curative intent). Prior history of brain metastasis (unless previously treated, asymptomatic and stable for at least 3 months) or organ transplant. Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study treatment. Active bleeding during the last 4 weeks prior to screening or in the investigator's judgment, the existence of high bleeding tendency lesions such as active gastrointestinal ulcers or prominent esophageal or gastric varices. Significant cardiovascular disease, including: Heart disease classified as New York Heart Association class III or IV. Ongoing uncontrolled hypertension. History of congenital long QT syndrome. Ongoing prolonged QT interval corrected for heart rate using Fridericia's method (QTcF) defined as ≥ 470 msec. History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation). Subjects with atrial fibrillation, that is well controlled with treatment, can be enrolled. Active heart disease including symptomatic heart failure (NYHA class 3 or 4), unstable angina pectoris, uncontrolled cardiac arrhythmia or interstitial lung disease. Prolonged QTcF interval >480 msec. Ongoing active, uncontrolled infection (must be afebrile for > 48 hours off antibiotics). With the exception of alopecia, any unresolved toxicities from prior therapy ≥Common Terminology Criteria for Adverse Events (CTCAE) Grade 2. Pregnancy or breastfeeding. (Women must not be pregnant or breastfeeding since study drugs may harm the fetus or child. All females of childbearing potential [not surgically sterilized and between menarche and 1 year post menopause] must have a negative screening pregnancy test.) History of human immunodeficiency virus infection. History of autoimmune disease. Ascertained hypersensitivity to gemcitabine, cisplatin, camrelizumab or apatinib, or drugs with similar chemical structures, or its inactive components. If there is suspicion that the subject may have an allergy, the subject should be excluded. Psychiatric illness, other significant medical illness, or social situation which, in the investigator's opinion, would limit compliance or ability to comply with study requirements. Judgment by the investigators that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dongsheng Zhang, M.D., Ph.D.
Phone
86-02087343795
Email
zhangdsh@sysucc.org.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dongsheng Zhang, M.D., Ph.D.
Organizational Affiliation
Sun Yat-sen University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cancer center of SunYat-sen University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Phase Ib/II Clinical Study of Camrelizumab and Apatinib Plus GP in the Treatment of Advanced Biliary Tract Cancer

We'll reach out to this number within 24 hrs