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Two-cohort Study of Toripalimab(PD1)+Lenvatnib, or Gemox+Lenvatinib in Advanced Intrahepatic Cholangiocarcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04361331
Recruitment Status : Recruiting
First Posted : April 24, 2020
Last Update Posted : April 24, 2020
Information provided by (Responsible Party):
Shanghai Zhongshan Hospital

Brief Summary:
We aim to explore the effects and safety of the two cohorts of toripalimab combined with lenvatinib or gemox combined with lenvatinib as first-line therapy in advanced or unresectable intrahepatic cholangiocarcinoma

Condition or disease Intervention/treatment Phase
Cholangiocarcinoma, Intrahepatic Drug: Lenvatinib combined with gemox Drug: Toripalimab combined with lenvatinib Phase 2

Detailed Description:
For advanced intrahepatic cholangiocarcinoma (ICC) that cannot be surgically removed or accompanied by metastasis, the NCCN guidelines (NCCN guidelines hepatobiliary cancer, 2019) recommend that the current treatment options are limited, mainly recommending gemcitabine combined with platinum-based antitumor drugs (cisplatin, oxaliplatin, etc.) chemotherapy as first-line treatment. Adding targeted drugs can enhance the anti-tumor effect. For those with microsatellite instability, it is recommended to add anti-PD1(programmed cell death protein 1) antibody. Gemox chemotherapy (oxaliplatin + gemcitabine) has been used in the treatment of advanced intrahepatic cholangiocarcinoma, but the efficacy is still not satisfactory. Lenvatinib is a small-molecule multi-kinase inhibitor that is currently approved for first-line treatment of advanced hepatocellular carcinoma. In recent years, the anti-PD1 antibody has shown efficacy in the treatment of primary liver cancer. Lenvatinib combined with anti-PD1 antibody or chemotherapy may have a better effect than single use for advanced ICC. At present, lenvatinib combined with anti-PD1 antibody or lenvatinib combined with Gemox in the first-line treatment of advanced ICC has not been reported.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Arm1: toripalimab combined with lenvatinib, Arm 2: lenvatinib combined with Gemox
Masking: None (Open Label)
Masking Description: Random number table grouping
Primary Purpose: Treatment
Official Title: A Randomized, Open, Two-cohort Phase 2 Study of Toripalimab(PD1) Combined With Lenvatnib, or Gemox Chemotherapy Combined With Lenvatinib as First-line Therapy in Patients With Advanced or Unresectable Intrahepatic Cholangiocarcinoma
Actual Study Start Date : March 6, 2020
Estimated Primary Completion Date : December 6, 2020
Estimated Study Completion Date : December 6, 2021

Arm Intervention/treatment
Toripalimab combined with lenvatinib
  1. Toripalimab: 240 mg, intravenous infusion, Q3W;
  2. Lenvatinib: 8mg (body weight <60kg) or 12mg (body weight ≥60kg), qd;
Drug: Toripalimab combined with lenvatinib
Toripalimab combined with lenvatinib

Lenvatinib combined with gemox
  1. Lenvatinib: 8mg (body weight <60kg) or 12mg (body weight ≥60kg), qd
  2. Gemox chemotherapy D1: Oxaliplatin 85mg / m2, Gemcitabine 1g / m2 D8: Gemcitabine 1g / m2 Three weeks are a course, a total of 6-8 courses
Drug: Lenvatinib combined with gemox
Arm2: Lenvatinib + gemox
Other Name: gemox chemotherapy

Primary Outcome Measures :
  1. Objective response rate [ Time Frame: 12 months ]
    Objective response rate of advanced and unresectable intrahepatic cholangiocarcinoma

Secondary Outcome Measures :
  1. Safety: the potential side effects [ Time Frame: 12 months ]
    The potential side effects

  2. Overall survival [ Time Frame: 12 months ]
    From the beginning date of combined therapy to the date of death

  3. Progression free survival [ Time Frame: 12 months ]
    From the beginning date of combined therapy to disease progression or death, whichever occurs first.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 1. The patient must be required to sign an informed consent; 2. Age 18-75 years old, male or female; 3. ECOG performance status score (PS score) 0 or 1 point; 4. Child-Pugh score A; 5. Intrahepatic cholangiocarcinoma confirmed by histopathology; agree to provide previously stored tumor tissue samples or fresh biopsy tumor lesions; 6. Unresectable ICC patients or postoperative ICC recurrence and metastasis, without systematic treatment within 6 months; 7. The functional indicators of vital organs meet the following requirements

    1. Neutrophils ≥1.5 * 109 / L; platelets ≥100 * 109 / L; hemoglobin ≥9g / dl; serum albumin ≥3g/dl;
    2. Thyroid stimulating hormone (TSH) ≤ 1 times the upper limit of normal value(ULN), T3 and T4 are in the normal range;
    3. Bilirubin ≤ 1.5 times ULN; ALT and AST ≤ 3 times ULN;
    4. Serum creatinine ≤ 1.5 times ULN, creatinine clearance rate ≥ 60ml/min (calculated using Cockcroft-Gault formula); 8. Subject has at least 1 measurable lesion (according to RECIST1.1); 9. Non-lactating or pregnant women, contraception during or 3 months after treatment.

Exclusion Criteria:

  • 1. Pathological diagnosis of hepatocellular carcinoma, mixed hepatocellular carcinoma and other non-cholangiocarcinoma malignancies; 2. Existing or concurrently suffering from other malignant tumors, except for fully treated non-melanoma skin cancer, cervical carcinoma in situ, and papillary thyroid cancer; 3. Have used lenvatinib or gemcitabine-based chemotherapy within 6 months or have used PD1 monoclonal antibody and PD-L1 monoclonal antibody treatment; 4. Severe cardiopulmonary and renal dysfunction; 5. Hypertension that is difficult to control by the drug (systolic blood pressure (BP) ≥140 mmHg and / or diastolic blood pressure ≥90 mmHg) (based on the average of ≥3 BP readings obtained from ≥2 measurements); 6. Abnormal blood coagulation function (PT> 14s), have bleeding tendency or are receiving thrombolysis or anticoagulation treatment; 7. HBV DNA> 2000 copies/ml and HCV RNA>1000 after antiviral treatment; 8. Have a history of esophagogastric varices, with significant clinically significant bleeding symptoms or a clear tendency to appear within 3 months before enrollment; 9. Active infection requiring systemic treatment and treatment; patients with active tuberculosis infection within 1 year before enrollment; a history of active tuberculosis infection more than 1 year before enrollment, have not received regular anti-TB treatment or tuberculosis Still in the active period; 10. Human immunodeficiency virus (HIV, HIV1/2 antibody) positive; 11. Have a history of psychotropic substance abuse, alcohol or drug abuse; 12. Known to have a history of severe allergies to any monoclonal antibodies, anti-angiogenic targeted drugs, and platinum or gemcitabine; 13. Other factors that may affect the safety of subjects or test compliance as judged by the investigator. Such as serious illness (including mental illness) requiring combined treatment, severe laboratory abnormalities, or other family or social factors.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04361331

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Contact: Xiao-yong Huang, MD +8615021519215
Contact: Guo-ming Shi, MD +8613916969578

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Huang xiaoyong Recruiting
Shanghai, China, 200032
Contact: Xiao-yong Huang, MD    +8615021519215   
China, 上海
Zhongshan hospital Recruiting
Shanghai, 上海, China, 200032
Contact: xiaoyong Huang, MD    +8615021519215   
Principal Investigator: Jian Zhou         
Sponsors and Collaborators
Shanghai Zhongshan Hospital
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Principal Investigator: Jian Zhou, MD & PhD Shanghai Zhongshan Hospital
Publications of Results:

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Responsible Party: Shanghai Zhongshan Hospital Identifier: NCT04361331    
Other Study ID Numbers: zs-ICC-2020
First Posted: April 24, 2020    Key Record Dates
Last Update Posted: April 24, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Shanghai Zhongshan Hospital:
intrahepatic Cholangiocarcinoma
Gemox chemotherapy
Programmed cell death protein 1 antibody
Additional relevant MeSH terms:
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Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action