Combined Therapy Using Oxaliplatin and Gemcitabine Chemotherapy, Lenvatinib and PD1 Antibody (JS001) for Patients With Advanced and Unresectable Intrahepatic Cholangiocarcinoma

July 5, 2021 updated by: Shanghai Zhongshan Hospital

a Single-arm Study of Combined Therapy Using Oxaliplatin and Gemcitabine Chemotherapy, Lenvatinib and Programmed Cell Death Protein 1 Antibody (JS001) for Patients With Advanced and Unresectable Intrahepatic Cholangiocarcinoma

In this phase 2 study, the investigators aim to evaluate the effects and safety of combined therapy using oxaliplatin and gemcitabine chemotherapy, Lenvatinib and immune checkpoint inhibitor PD-1 antibody (JS001) for patients with advanced and unresectable intrahepatic cholangiocarcinoma

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Most intrahepatic cholangiocarcinoma (ICC) patients are often accompanied by local or distant metastases and lose the opportunity for surgical resection. For patients with unresectable ICC who have been in stages IIIb and IV (AJCC/UICC, V2, 2018), the survival time is less than 4 months, and there is currently no standard treatment. The Gemox chemotherapy (oxaliplatin + gemcitabine) has been used in the treatment of advanced intrahepatic cholangiocarcinoma, but the efficacy is still unsatisfactory. Lenvatinib is a small molecule multi-kinase inhibitor, the main targets including VEGFR1-3, fibroblast growth factor receptor 1-4, PDGFRα, RET(ret proto-oncogene ), KIT(KIT proto-oncogene, receptor tyrosine kinase), have anti-angiogenic effects, have been proven effective in hepatocellular carcinoma. In recent years, monoclonal antibodies against programmed cell death protein 1 (PD1) have shown remarkable therapeutic effects in the treatment of various solid tumors. Combined with other means such as chemotherapy and targeted drugs is an important direction to improve the therapeutic effect of immunological checkpoint inhibitors. In this study, the investigators aim to evaluate the effects and safety of Gemox chemotherapy combined with Lenvatinib and immune checkpoint inhibitor PD-1 antibody (JS001) for patients with advanced and unresectable intrahepatic cholangiocarcinoma.

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200032
        • Zhongshan Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. The patient must be required to sign an informed consent form;
  2. age 18-75 years old, male or female;
  3. Eastern Cooperative Oncology Group (ECOG) fitness status score (PS score) 0;
  4. Child-Pugh score A;
  5. Histopathologically confirmed intrahepatic cholangiocarcinoma; consent to provide previously stored tumor tissue specimens or fresh biopsy tumor lesions;
  6. unresectable ICC patients;
  7. Functional indicators of vital organs meet the following requirements a Neutrophils ≥1.5*109/L; platelets≥100*109/L; hemoglobin≥9g/dl; serum albumin≥3g/dl; b Thyroid stimulating hormone (TSH) ≤ 1 times the upper limit of normal value(ULN), T3, T4 are in the normal range; c bilirubin ≤ 1.5 times ULN; Alanine aminotransferase （ALT） and Aspartate aminotransferase （AST） ≤ 1.5 times ULN; d serum creatinine ≤ 1.5 ULN, creatinine clearance rate ≥ 60ml / min;
  8. The subject has at least 1 measurable liver lesion or non-liver lesion (according to RECIST 1.1);
  9. Non-lactating or pregnant women, contraception during or after 3 months of treatment.

Exclusion Criteria:

  1. pathological diagnosis of hepatocellular carcinoma, mixed liver cancer and other non-cholangiocarcinoma malignant tumor components;
  2. patients who have received previous treatment with PD1 antibody, programmed death ligand -1 （PDL1） antibody or cytotoxic T lymphocyte-associated antigen-4 （CTLA4） antibody;
  3. with other malignant tumors, except for fully treated non-melanoma skin cancer, cervical carcinoma in situ, and papillary thyroid carcinoma;
  4. active tuberculosis infection. Patients with active tuberculosis infection within 1 year prior to enrollment; had a history of active tuberculosis infection more than 1 year before enrollment, did not receive formal anti-tuberculosis treatment or tuberculosis is still active;
  5. Have an active, known or suspected autoimmune disease. Subjects who require only hormone replacement therapy for hypothyroidism and skin diseases that do not require systemic therapy may be enrolled;
  6. previous interstitial lung disease, or (non-infectious) pneumonia and need oral or intravenous steroid therapy;
  7. Long-term systemic hormones (dose equivalent to >10 mg prednisone/day) or any other form of immunosuppressive therapy are required. Subjects using inhaled or topical corticosteroids may be enrolled;
  8. severe cardiopulmonary and renal dysfunction;
  9. suffering from high blood pressure, and can not be well controlled by antihypertensive drugs (systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg);
  10. abnormal blood coagulation (PT>14s), with bleeding tendency or receiving thrombolytic or anticoagulant therapy;
  11. hepatitis B virus （HBV） DNA>2000 copies/ml, hepatitis C virus （HCV） RNA>1000;
  12. Significant clinically significant bleeding symptoms or a clear tendency to appear within 3 months prior to enrollment;
  13. active infections requiring systemic treatment;
  14. Human immunodeficiency virus (HIV) positive;
  15. History of psychotropic substance abuse, alcohol abuse or drug abuse;
  16. has a history of allergy to platinum;
  17. Other factors that may influence the safety of the subject or the compliance of the test by the investigator. Serious illnesses (including mental illness), severe laboratory tests, or other family or social factors that require combined treatment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Combined therapy using Gemox, Lenvatinib and PD1
  1. Gemox chemotherapy Day1 oxaliplatin 85mg/m2+ gemcitabine 1g/m2, Day8 gemcitabine 1g/m2 Three weeks is a course of treatment with a total of 6 courses.
  2. Lenvatinib (8mg/d), continuous use for 1 year.
  3. PD-1 antibody (JS001) (240mg every 3 weeks), continuous use for 1 year.
Drug: combined therapy using oxaliplatin and gemcitabine chemotherapy, Lenvatinib and PD1 antibody (JS001)
  1. Gemox chemotherapy Day1 oxaliplatin 85mg/m2+ gemcitabine 1g/m2, Day8 gemcitabine 1g/m2 Three weeks is a course of treatment with a total of 6 courses.
  2. Lenvatinib (8mg/d), continuous use for 1 year.
  3. PD-1 antibody (JS001) (240mg every 3 weeks), continuous use for 1 year.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate
Time Frame: 12 months
Objective response rate of advanced and unresectable intrahepatic cholangiocarcinoma in combination therapy
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
safety: the potential side effects
Time Frame: 12 months
the potential side effects
12 months
overall survival
Time Frame: 12 months
From the beginning date of combined therapy to the date of death
12 months
Progression free survival
Time Frame: 12 months
From the beginning date of combined therapy to the date of disease progression
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai Zhongshan Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 10, 2019

Primary Completion (Actual)

January 10, 2020

Study Completion (Anticipated)

November 10, 2021

Study Registration Dates

First Submitted

May 14, 2019

First Submitted That Met QC Criteria

May 14, 2019

First Posted (Actual)

May 15, 2019

Study Record Updates

Last Update Posted (Actual)

July 7, 2021

Last Update Submitted That Met QC Criteria

July 5, 2021

Last Verified

July 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • zs-ICC-2019

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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