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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT03951597
Other study ID # zs-ICC-2019
Secondary ID
Status Active, not recruiting
Phase Phase 2
First received
Last updated
Start date May 10, 2019
Est. completion date November 10, 2021

Study information

Verified date July 2021
Source Shanghai Zhongshan Hospital
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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


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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 30
Est. completion date November 10, 2021
Est. primary completion date January 10, 2020
Accepts healthy volunteers No
Gender All
Age group 18 Years to 75 Years
Eligibility 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 Design


Related Conditions & MeSH terms


Intervention

Drug:
combined therapy using oxaliplatin and gemcitabine chemotherapy, Lenvatinib and PD1 antibody (JS001)
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. Lenvatinib (8mg/d), continuous use for 1 year. PD-1 antibody (JS001) (240mg every 3 weeks), continuous use for 1 year.

Locations

Country Name City State
China Zhongshan Hospital Shanghai Shanghai

Sponsors (1)

Lead Sponsor Collaborator
Shanghai Zhongshan Hospital

Country where clinical trial is conducted

China, 

References & Publications (3)

André 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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Objective response rate Objective response rate of advanced and unresectable intrahepatic cholangiocarcinoma in combination therapy 12 months
Secondary safety: the potential side effects the potential side effects 12 months
Secondary overall survival From the beginning date of combined therapy to the date of death 12 months
Secondary Progression free survival From the beginning date of combined therapy to the date of disease progression 12 months
See also
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Terminated NCT03267940 - Study of PEGPH20 With Cisplatin (CIS) and Gemcitabine (GEM); PEGPH20 With Atezolizumab (ATEZO), CIS, and GEM; and CIS and GEM Alone in Participants With Previously Untreated, Unresectable, Locally Advanced, or Metastatic Intrahepatic and Extrahepatic Cholangiocarcinoma and Gallbladder Adenocarcinoma Phase 1
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