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Cholangiocarcinoma, IntrahepaticPhase 2NCT04361331

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

A Phase 2 study testing Lenvatinib combined with gemox and Toripalimab combined with lenvatinib in people with Cholangiocarcinoma, Intrahepatic, run by Shanghai Zhongshan Hospital at 2 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Cholangiocarcinoma, Intrahepatic
What is being tested?
Lenvatinib combined with gemox and Toripalimab combined with lenvatinib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
61 participants
Where
2 sitesChina
Study dates
6 Mar 2020to 1 Sep 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
  • 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.

Who cannot join

  • 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.

Trial locations and contacts

2 sites in 1 country.

China2 sites
  • Zhongshan hospital

    Shanghai, Shanghai Municipality, 200032

  • Huang xiaoyong

    Shanghai, 200032

Other trials in China

About this study

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

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

Read the 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.

Being tested
Lenvatinib combined with gemox, Toripalimab combined with lenvatinib
Keywords
intrahepatic Cholangiocarcinoma, Lenvatinib, Gemox chemotherapy, Programmed cell death protein 1 antibody
Medical subject headings
Cholangiocarcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Lenvatinib combined with gemoxDrug

    Also called gemox chemotherapy

    Arm2: Lenvatinib + gemox

  • Toripalimab combined with lenvatinibDrug

    Toripalimab combined with lenvatinib

Study groups in NCT04361331
Study groupRoleWhat they receive
Toripalimab combined with lenvatinibOther1. Toripalimab: 240 mg, intravenous infusion, Q3W; 2. Lenvatinib: 8mg (body weight <60kg) or 12mg (body weight ≥60kg), qd;
Receives: Drug: Toripalimab combined with lenvatinib
Lenvatinib combined with gemoxOther1. 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
Receives: Drug: Lenvatinib combined with gemox

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective response rate

    Objective response rate of advanced and unresectable intrahepatic cholangiocarcinoma

    Measured: 12 months

Secondary outcomes (3)
  1. Safety: the potential side effects

    The potential side effects

    Measured: 12 months

  2. Overall survival

    From the beginning date of combined therapy to the date of death

    Measured: 12 months

  3. Progression free survival

    From the beginning date of combined therapy to disease progression or death, whichever occurs first.

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Apr 2020
  2. Study start6 Mar 2020
  3. Primary completion1 Sep 2023
  4. Study completion1 Sep 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Arm1: toripalimab combined with lenvatinib, Arm 2: lenvatinib combined with Gemox
Masking
None (open label)
Enrolment
61 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04361331
Sponsor's protocol ID
zs-ICC-2020
Status last verified
Feb 2025
First submitted
22 Apr 2020
Last updated
7 Feb 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 15319238
  • 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.

    PubMed 29433850
  • 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.

    PubMed 28434648
  • 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.

    PubMed 29875066
  • 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.

    PubMed 41121202

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lenvatinib combined with gemox and Toripalimab combined with lenvatinib in people with Cholangiocarcinoma, Intrahepatic, run by Shanghai Zhongshan Hospital at 2 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04361331, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2025.

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