NCT04506281

Brief Summary

A randomized controlled, multi-center, open, phase II clinical study is designed to target patients with resectable intrahepatic cholangiocarcinoma with high-risk recurrence factors which has extremely low postoperative recurrence-free survival. In this study, we aim to compare the prognosis in intrahepatic cholangiocarcinoma between Toripalimab combined with Lenvatinib and GEMOX neoadjuvant treatment and the current clinical surgical treatment (traditional group).

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
128

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Aug 2020

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 7, 2020

Completed
3 days until next milestone

First Posted

Study publicly available on registry

August 10, 2020

Completed
Same day until next milestone

Study Start

First participant enrolled

August 10, 2020

Completed
12 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2021

Completed
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2023

Completed
Last Updated

August 10, 2020

Status Verified

August 1, 2020

Enrollment Period

12 months

First QC Date

August 7, 2020

Last Update Submit

August 7, 2020

Conditions

Cholangiocarcinoma, Intrahepatic

Keywords

intrahepatic CholangiocarcinomaLenvatinibGemox chemotherapyProgrammed cell death protein 1 antibody

Outcome Measures

Primary Outcomes (1)

  • Event-free survival

    From randomization to the occurrence of the following events: disease progression prevents radical surgery; local or distant recurrence; second primary tumor; death due to various causes.

    18 months

Secondary Outcomes (4)

  • Overall survival

    24 months

  • Objective response rate

    6 months

  • Pathological remission rate

    6 months

  • Adverse events

    12 months

Study Arms (2)

Neoadjuvant treatment

EXPERIMENTAL

1. Gemox chemotherapy: Day1 Oxaliplatin 85mg/m2+ gemcitabine 1g/m2, Day 8 gemcitabine 1g/m2 Three weeks is a course of treatment, a total of 3 courses. 2. Lenvatinib (8mg/d) for 9 weeks of continuous use. 3. Toripalimab (240mg, once every 3 weeks), used 3 times. Evaluate the resectability of the operation within 2-4 weeks after the end of the neoadjuvant treatment course, and implement radical resection. All patients after resection use capecitabine 2500mg/m2 twice a day for 2 weeks, stopping for 1 week as a course of treatment, totaling 8 courses

Drug: neoadjuvant treatment

Traditional group

NO INTERVENTION

No anti-tumor drug treatment before surgery. All patients undergoing resection use capecitabine 2500mg/m2 twice a day, stopping for 1 week as a course of treatment, totaling 8 courses.

Interventions

neoadjuvant treatmentDRUG

PD1 antibody (Toripalimab) combined with GEMOX chemotherapy and Lenvatinib neoadjuvant treatment

Neoadjuvant treatment

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • \) Sign written informed consent 2) Male or female patients aged 18-70; 3) ECOG score 0 points, Child-Pugh rating A; 4) Clinically diagnosed as ICC as a potential entry, the neoadjuvant group must be histopathologically diagnosed as intrahepatic cholangiocarcinoma before neoadjuvant, and the traditional group must be pathologically confirmed as intrahepatic cholangiocarcinoma after surgery; 5) Resectable ICC patients with high risk factors for recurrence (tumor diameter\>5cm or imaging vascular invasion, multiple tumor nodules or hilar lymph node metastasis or preoperative CA199\>200U/ml); 6) The functional indicators of important organs meet the following requirements
  • Neutrophils≥1.5\*109/L; platelets≥90\*109/L; hemoglobin≥9g/dl; serum albumin≥3.5g/dl;
  • Coagulation function: International standardization (prothrombin time) ratio (INR) \<1.2;
  • T3 and T4 do not exceed the normal upper and lower limits by 2 times;
  • Bilirubin ≤ 1.5 times the upper limit of normal; ALT and AST ≤ 3 times the upper limit of normal;
  • Serum creatinine ≤ 1.5 times the upper limit of normal, creatinine clearance ≥ 60ml/min; 7) The subject has at least 1 measurable liver disease (according to RECIST1.1); 8) For women who are not breastfeeding or pregnant, use contraception during treatment or 3 months after the end of treatment.

You may not qualify if:

  • \) Pathological diagnosis of hepatocellular carcinoma, mixed hepatocellular carcinoma and other non-biliary cell carcinoma malignant tumor components; 2) Patients who relapse after surgery, have received PD1 antibody, PDL1 antibody or CTLA4 antibody, lenvatinib, chemotherapy in the past; participated in other clinical trials 30 days before screening; 3) Past or simultaneous suffering from other malignant tumors, except for fully treated non-melanoma skin cancer, cervical carcinoma in situ and thyroid papillary carcinoma; 4) Active tuberculosis infection. Patients with active tuberculosis infection within 1 year before enrollment; a history of active tuberculosis infection more than 1 year before enrollment, no formal anti-tuberculosis treatment or tuberculosis is still active; 5) Suffer from active, known or suspected autoimmune diseases. Subjects with hypothyroidism who only need hormone replacement therapy and skin diseases without systemic therapy can be selected; 6) Past interstitial lung disease, or (non-infectious) pneumonia and need oral or intravenous steroid therapy; 7) Long-term use of systemic hormones (dose equivalent to \>10mg prednisone/day) or any other form of immunosuppressive therapy is required. Subjects using inhaled or topical corticosteroids can be selected; 8) Active infections that require systemic treatment; 9) Human immunodeficiency virus (HIV, HIV1/2 antibody) positive; 10) A history of psychotropic drug abuse, alcohol or drug abuse; 11) Significant clinically significant bleeding symptoms or a clear tendency to appear within 3 months before enrollment; 12) Suspected of being allergic to study drugs; 13) Suffer from hypertension, and cannot be well controlled by antihypertensive medication (systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg); 14) After antiviral therapy, HBvDNA\>104 copies/ml, HCV RNA\>1000; 15) Accompanied by ascites, hepatic encephalopathy, Gilbert syndrome, sclerosing cholangitis, etc. Combined with insufficiency of other organs, it is expected that they cannot accept general anesthesia or hepatectomy; 16) Other factors judged by the investigator that may affect the safety of the subject or the compliance of the trial. Such as serious illnesses (including mental illness) that require combined treatment, serious laboratory abnormalities, or other family or social factors.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Zhongshan hospital

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

Related Publications (5)

  • Shaib Y, El-Serag HB. The epidemiology of cholangiocarcinoma. Semin Liver Dis. 2004 May;24(2):115-25. doi: 10.1055/s-2004-828889.

    PMID: 15192785RESULT

  • Shen WF, Zhong W, Xu F, Kan T, Geng L, Xie F, Sui CJ, Yang JM. Clinicopathological and prognostic analysis of 429 patients with intrahepatic cholangiocarcinoma. World J Gastroenterol. 2009 Dec 21;15(47):5976-82. doi: 10.3748/wjg.15.5976.

    PMID: 20014463RESULT

  • Cho SY, Park SJ, Kim SH, Han SS, Kim YK, Lee KW, Lee SA, Hong EK, Lee WJ, Woo SM. Survival analysis of intrahepatic cholangiocarcinoma after resection. Ann Surg Oncol. 2010 Jul;17(7):1823-30. doi: 10.1245/s10434-010-0938-y. Epub 2010 Feb 18.

    PMID: 20165987RESULT

  • Fisher SB, Patel SH, Kooby DA, Weber S, Bloomston M, Cho C, Hatzaras I, Schmidt C, Winslow E, Staley CA 3rd, Maithel SK. Lymphovascular and perineural invasion as selection criteria for adjuvant therapy in intrahepatic cholangiocarcinoma: a multi-institution analysis. HPB (Oxford). 2012 Aug;14(8):514-22. doi: 10.1111/j.1477-2574.2012.00489.x. Epub 2012 May 22.

    PMID: 22762399RESULT

  • Yamashita Y, Taketomi A, Morita K, Fukuhara T, Ueda S, Sanefuji K, Iguchi T, Kayashima H, Sugimachi K, Maehara Y. The impact of surgical treatment and poor prognostic factors for patients with intrahepatic cholangiocarcinoma: retrospective analysis of 60 patients. Anticancer Res. 2008 Jul-Aug;28(4C):2353-9.

    PMID: 18751418RESULT

MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasms

Intervention Hierarchy (Ancestors)

Combined Modality TherapyTherapeutics

Study Officials

  • Jia Fan, MD & PhD

    Shanghai Zhongshan Hospital

    STUDY CHAIR

Central Study Contacts

xiao-yong Huang, MD

CONTACT

+8615021519215huang.xiaoyong@zs-hospital.sh.cn

Guo-ming Shi, MD

CONTACT

+8613916969578shi.guoming@zs-hospital.sh.cn

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 7, 2020

First Posted

August 10, 2020

Study Start

August 10, 2020

Primary Completion

August 1, 2021

Study Completion

August 1, 2023

Last Updated

August 10, 2020

Record last verified: 2020-08

Data Sharing

IPD Sharing
Will not share

Locations

CN(1)