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

NCT03951597 | Unknown Phase 2

• 1 other identifier: zs-ICC-2019
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Cholangiocarcinoma, Intrahepatic

Keywords

intrahepatic cholangiocarcinoma; oxaliplatin and gemcitabine chemotherapy; Lenvatinib; programmed cell death protein 1 antibody

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  Objective response rate of advanced and unresectable intrahepatic cholangiocarcinoma in combination therapy

  12 months

Secondary Outcomes (3)

• safety: the potential side effects

  12 months

• overall survival

  12 months

• Progression free survival

  12 months

Study Arms (1)

Combined therapy using Gemox, Lenvatinib and PD1

EXPERIMENTAL

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)

Interventions

combined therapy using oxaliplatin and gemcitabine chemotherapy, Lenvatinib and PD1 antibody (JS001) DRUG

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.

Combined therapy using Gemox, Lenvatinib and PD1

Eligibility Criteria

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

You may qualify if:

• The patient must be required to sign an informed consent form;
• age 18-75 years old, male or female;
• Eastern Cooperative Oncology Group (ECOG) fitness status score (PS score) 0;
• Child-Pugh score A;
• Histopathologically confirmed intrahepatic cholangiocarcinoma; consent to provide previously stored tumor tissue specimens or fresh biopsy tumor lesions;
• unresectable ICC patients;
• 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;
• The subject has at least 1 measurable liver lesion or non-liver lesion (according to RECIST 1.1);
• Non-lactating or pregnant women, contraception during or after 3 months of treatment.

You may not qualify if:

• pathological diagnosis of hepatocellular carcinoma, mixed liver cancer and other non-cholangiocarcinoma malignant tumor components;
• patients who have received previous treatment with PD1 antibody, programmed death ligand -1 （PDL1） antibody or cytotoxic T lymphocyte-associated antigen-4 （CTLA4） antibody;
• with other malignant tumors, except for fully treated non-melanoma skin cancer, cervical carcinoma in situ, and papillary thyroid carcinoma;
• 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;
• 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;
• previous interstitial lung disease, or (non-infectious) pneumonia and need oral or intravenous steroid therapy;
• 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;
• severe cardiopulmonary and renal dysfunction;
• suffering from high blood pressure, and can not be well controlled by antihypertensive drugs (systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg);
• abnormal blood coagulation (PT\>14s), with bleeding tendency or receiving thrombolytic or anticoagulant therapy;
• hepatitis B virus （HBV） DNA\>2000 copies/ml, hepatitis C virus （HCV） RNA\>1000;
• Significant clinically significant bleeding symptoms or a clear tendency to appear within 3 months prior to enrollment;
• active infections requiring systemic treatment;
• Human immunodeficiency virus (HIV) positive;
• History of psychotropic substance abuse, alcohol abuse or drug abuse;

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead

Study Sites (1)

Zhongshan Hospital

Shanghai, Shanghai Municipality, 200032, China

Location

Related Publications (4)

• Andre T, Tournigand C, Rosmorduc O, Provent S, Maindrault-Goebel F, Avenin D, Selle F, Paye F, Hannoun L, Houry S, Gayet B, Lotz JP, de Gramont A, Louvet C; GERCOR Group. Gemcitabine combined with oxaliplatin (GEMOX) in advanced biliary tract adenocarcinoma: a GERCOR study. Ann Oncol. 2004 Sep;15(9):1339-43. doi: 10.1093/annonc/mdh351.

  PMID: 15319238 BACKGROUND

• Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, Baron A, Park JW, Han G, Jassem J, Blanc JF, Vogel A, Komov D, Evans TRJ, Lopez C, Dutcus C, Guo M, Saito K, Kraljevic S, Tamai T, Ren M, Cheng AL. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018 Mar 24;391(10126):1163-1173. doi: 10.1016/S0140-6736(18)30207-1.

  PMID: 29433850 BACKGROUND

• El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, Kim TY, Choo SP, Trojan J, Welling TH Rd, Meyer T, Kang YK, Yeo W, Chopra A, Anderson J, Dela Cruz C, Lang L, Neely J, Tang H, Dastani HB, Melero I. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017 Jun 24;389(10088):2492-2502. doi: 10.1016/S0140-6736(17)31046-2. Epub 2017 Apr 20.

  PMID: 28434648 BACKGROUND

• Shi GM, Huang XY, Wu D, Sun HC, Liang F, Ji Y, Chen Y, Yang GH, Lu JC, Meng XL, Wang XY, Sun L, Ge NL, Huang XW, Qiu SJ, Yang XR, Gao Q, He YF, Xu Y, Sun J, Ren ZG, Fan J, Zhou J. Toripalimab combined with lenvatinib and GEMOX is a promising regimen as first-line treatment for advanced intrahepatic cholangiocarcinoma: a single-center, single-arm, phase 2 study. Signal Transduct Target Ther. 2023 Mar 17;8(1):106. doi: 10.1038/s41392-023-01317-7.

  PMID: 36928584 DERIVED

MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

lenvatinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Jian Zhou, MD&PhD

  Fudan University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2019
• First Posted: May 15, 2019
• Study Start: May 10, 2019
• Primary Completion: January 10, 2020
• Study Completion: November 10, 2021
• Last Updated: July 7, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)