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

NCT04361331 | Completed Phase 2

• 1 other identifier: zs-ICC-2020
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 2

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

Conditions

Cholangiocarcinoma, Intrahepatic

Keywords

intrahepatic Cholangiocarcinoma; Lenvatinib; Gemox chemotherapy; Programmed cell death protein 1 antibody

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  Objective response rate of advanced and unresectable intrahepatic cholangiocarcinoma

  12 months

Secondary Outcomes (3)

• Safety: the potential side effects

  12 months

• Overall survival

  12 months

• Progression free survival

  12 months

Study Arms (2)

Toripalimab combined with lenvatinib

OTHER

1. Toripalimab: 240 mg, intravenous infusion, Q3W; 2. Lenvatinib: 8mg (body weight \<60kg) or 12mg (body weight ≥60kg), qd;

Drug: Toripalimab combined with lenvatinib

Lenvatinib combined with gemox

OTHER

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

Interventions

Lenvatinib combined with gemox DRUG

Arm2: Lenvatinib + gemox

Also known as: gemox chemotherapy

Lenvatinib combined with gemox

Toripalimab combined with lenvatinib DRUG

Toripalimab combined with lenvatinib

Toripalimab combined with lenvatinib

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; 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
• Neutrophils ≥1.5 \* 109 / L; platelets ≥100 \* 109 / L; hemoglobin ≥9g / dl; serum albumin ≥3g/dl;
• Thyroid stimulating hormone (TSH) ≤ 1 times the upper limit of normal value(ULN), T3 and T4 are in the normal range;
• Bilirubin ≤ 1.5 times ULN; ALT and AST ≤ 3 times ULN;
• 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.

You may not qualify if:

• \. 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.

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead

Study Sites (2)

Zhongshan hospital

Shanghai, Shanghai Municipality, 200032, China

Location

Huang xiaoyong

Shanghai, 200032, China

Location

Related Publications (5)

• 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

• Zhu AX, Finn RS, Edeline J, Cattan S, Ogasawara S, Palmer D, Verslype C, Zagonel V, Fartoux L, Vogel A, Sarker D, Verset G, Chan SL, Knox J, Daniele B, Webber AL, Ebbinghaus SW, Ma J, Siegel AB, Cheng AL, Kudo M; KEYNOTE-224 investigators. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Lancet Oncol. 2018 Jul;19(7):940-952. doi: 10.1016/S1470-2045(18)30351-6. Epub 2018 Jun 3.

  PMID: 29875066 BACKGROUND

• Huang XY, Shi GM, Zheng ZT, Sun HC, Liang F, Ji Y, Chen Y, Yang GH, Hu ZQ, Lu JC, Meng XL, Guo XJ, Zhang CC, Fan J, Zhou J. Anti-PD1 antibody toripalimab combined with lenvatinib, or GEMOX chemotherapy combined with lenvatinib as first-line therapy in patients with advanced intrahepatic cholangiocarcinoma: a randomized, open, two-cohort Phase 2 Study. BMC Med. 2025 Oct 21;23(1):573. doi: 10.1186/s12916-025-04404-4.

  PMID: 41121202 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

  Shanghai Zhongshan Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Random number table grouping
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Arm1: toripalimab combined with lenvatinib， Arm 2: lenvatinib combined with Gemox

Study Record Dates

• First Submitted: April 22, 2020
• First Posted: April 24, 2020
• Study Start: March 6, 2020
• Primary Completion: September 1, 2023
• Study Completion: September 1, 2023
• Last Updated: February 7, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)