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

NCT05742750 | Unknown Phase 1

• 1 other identifier: 22-OBU-GD-EC-II-005
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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).

Conditions

Locally Advanced Biliary Tract Cancer; Metastatic Biliary Tract Cancer

Keywords

Biliary Tract Cancer

Outcome Measures

Primary Outcomes (3)

• 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

  up to day 22

• Recommended phase 2 dose(RP2D) of apatinib

  To determine a RP2D of apatinib for each population of biliary tract carcinoma subjects.

  12 weeks

• 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.

  up to 24 months

Secondary Outcomes (4)

• Adverse Events (AE)

  up to 24 months

• Disease Control Rate (DCR)

  up to 24 months

• Progression-Free Survival (PFS)

  up to 24 months

• Overall Survival (OS)

  up to 24 months

Study Arms (1)

Camrelizumab + apatinib and chemotherapies (gemcitabine and cisplatin)

EXPERIMENTAL

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

Drug: Camrelizumab and Apatinib Plus GP

Interventions

Camrelizumab and Apatinib Plus GP DRUG

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.

Also known as: Apatinib (Apatinib Mesylate Tablets, Jiangsu Hengrui Medicine, China), Camrelizumab (Carelizumab for Injection, Jiangsu Hengrui Medicine, China)

Camrelizumab + apatinib and chemotherapies (gemcitabine and cisplatin)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Jiangsu Hengrui Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

Cancer center of SunYat-sen University

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

camrelizumab; apatinib; Injections

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Dongsheng Zhang, M.D., Ph.D.

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dongsheng Zhang, M.D., Ph.D.

CONTACT

86-02087343795; zhangdsh@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief physician，professor

Study Record Dates

• First Submitted: February 15, 2023
• First Posted: February 24, 2023
• Study Start: March 1, 2023
• Primary Completion: December 30, 2023
• Study Completion: December 30, 2024
• Last Updated: February 24, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)