Tislelizumab(Anti PD-1), Lenvatinib and GEMOX Transformation in the Treatment of Potentially Resectable, Locally Advanced Biliary Tract Cancer

  • STATUS
    Recruiting
  • End date
    Oct 1, 2025
  • participants needed
    40
  • sponsor
    Shanghai Zhongshan Hospital
Updated on 19 December 2021

Summary

The aim of this study is to assess the R0 resection rate of tislelizumab combined with Lenvatinib and Gemox chemotherapy in the conversion therapy of potentially resectable locally advanced BTC.

Description

Translational therapy refers to methods such as chemotherapy, radiotherapy, immunotherapy, targeted and combined therapy to shrink tumors, reduce tumor biological behavior, and achieve secondary resection. The success rate of transformation depends on the objective response rate of the treatment method (Objective response rate, ORR). The latest review showed that 132 patients with unresectable ICC had undergone chemotherapy, chemoembolization, radiotherapy embolization or combination therapy, and 27 patients received downgrade resection. The research of our group using PD-1 antibody combined with lenvatinib and Gemox chemotherapy in the first-line treatment of unresectable advanced cholangiocarcinoma (NCT03951597, 2020ESMO, 2021ASCO) showed that the ORR was 80% and the disease control rate (DCR) It reached 93.3% (28/30), of which 3 cases underwent successful radical resection after downstage. These data suggest that PD1 monoclonal antibody combined with lenvatinib and Gemox chemotherapy may be an ideal conversion therapy for patients with potentially resectable advanced biliary system tumors, but there is currently no evidence-based basis.

This study explores the efficacy and safety of PD1 monoclonal antibody combined with Lenvatinib and Gemox chemotherapy in potentially resectable advanced BTC conversion therapy. It has certain clinical significance in order to increase the R0 surgical resection rate of BTC patients and improve patient survival.

Details
Condition Biliary Tract Cancer, PD-1 Antibody, Gemox, Lenvatinib
Treatment PD-1+Lenvatinib+GEMOX
Clinical Study IdentifierNCT05156788
SponsorShanghai Zhongshan Hospital
Last Modified on19 December 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

\. Male or female aged 18-70 2. The patient must sign an informed consent form before joining the group, understand and be willing to sign a written informed consent form 3\. Potentially resectable locally advanced BTC (including ICC, PBDT and GBC) confirmed by histology or cytology, agree to provide previously stored tumor tissue specimens or fresh biopsy tumor lesions for biomarker detection 4. Local progress, failure to achieve R0 resection, and no distant metastasis, with potential resection 5. At least one measurable lesion (RECIST 1.1) 6. Have never received systemic treatment for biliary tumors in the past 7. Eastern Cooperative Oncology Group (ECOG) performance status score ECOG PS 0-1 8. Liver function classification is Child-Pugh A 9. The bone marrow, liver and kidneys are fully functional and reach the following clinical laboratory evaluation standards within 7 days before treatment
Blood indicators
Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet ≥ 90 × 109/L
hemoglobin ≥ 90 g/L
Liver function indicators
AST and ALT are both ≤3×ULN (upper limit of normal value); total bilirubin
≤1.5×ULN
Kidney function indicators
Serum creatinine≤1.5×ULN
Coagulation index
International normalized ratio (INR) ≤ 1.2 or prothrombin time (PT) ≤ 1.2×ULN
Obstructive jaundice, after PTCD or ERCP treatment, if the liver function indicators meet
the requirements for entry, it can be considered for entry
If the subject has HBV or HCV infection, the following conditions must be met
For inactive/asymptomatic carriers of HBV, chronic, or active HBV
HBV deoxyribonucleic acid (DNA) <2000 copies/mL during the screening period. Remarks
Patients with HBV DNA>2000 copies/mL should be treated according to treatment guidelines
Patients who received antiviral drug treatment at the time of screening should have HBV-DNA
<2000 copies/mL and continue treatment during the study period
For subjects infected with HCV
If the infection is confirmed based on the detectable HCV ribonucleic acid RNA, such
subjects cannot be included in the group
If you are a fertile woman (that is, physically capable of getting pregnant), you must
agree to take effective contraceptive measures during the study period and within 120 days
after the last administration, and have urine within 7 days before the first study drug
administration Or the serum pregnancy test is negative
If you are a non-sterilized male, you need to agree to take effective contraceptive
measures during the study period and 120 days after the last dose
Life expectancy ≥ 3 months

Exclusion Criteria

Diagnosed as mixed type of periampullary carcinoma, hepatocellular carcinoma and
cholangiocarcinoma 2. Have received systemic treatment for biliary tumors in the past
Have previously received gemcitabine-based chemotherapy or TKI therapy or any tumor
immunotherapy (for example, PD-1/L1 inhibitors, CTLA-4 inhibitors, etc.) 4. Have a
history of severe hypersensitivity to other monoclonal antibodies 5. Allergy to
tislelizumab or any of its excipients; allergy to oxaliplatin and any of its
excipients; allergy to gemcitabine and any of its excipients; allergy to lenvatinib
and any of its excipients 6. The presence of pericardial effusion, uncontrollable
pleural effusion or clinically obvious ascites within 7 days before treatment is
defined as meeting the following criteria: (a) Ascites can be detected by physical
examination during screening, or (b) during screening, Ascites requires puncture
fluid
There is no clinical evidence of portal hypertension with esophageal or gastric
varices within 6 months before starting treatment
Any bleeding or thrombotic disease or any anticoagulant (such as warfarin or
similar drugs) that needs to monitor the international standardized ratio during
treatment within 6 months before the start of treatment 9. Has suffered from any
malignant tumors, except for the BTC studied in this clinical trial and locally
recurring cancers that have been cured (such as resected basal cell or squamous cell
skin cancer, superficial bladder cancer, cervical or breast cancer) Carcinoma in situ
occult carcinoma of the thyroid)
Any known central nervous system metastasis and/or leptomeningeal disease have
been present before treatment
A history of any active immunodeficiency or autoimmune disease and/or any
immunodeficiency or autoimmune disease that may recur at the time of screening
Note: Subjects with the following diseases can be selected
Type I diabetes Hypothyroidism (if only hormone replacement therapy can be used to control)
Controlled celiac disease Skin diseases that do not require systemic treatment (eg
vitiligo, psoriasis, hair loss) Any other disease that will not recur without external
triggers 12. Any disease requiring systemic treatment with corticosteroids (dose higher
than 10mg/day of prednisone or equivalent doses of similar drugs) or other
immunosuppressive agents in the 14 days before treatment
Remarks: Subjects who have currently or previously used any of the following steroid
regimens can be selected
In the absence of active autoimmune diseases, adrenaline replacement steroids are allowed
(prednisone ≤10mg/day or equivalent dose of similar drugs) Local, ophthalmic
intra-articular, intranasal and inhaled corticosteroids with minimal systemic absorption
Prophylactic short-term use (≤7 days) corticosteroids (for example, allergy to contrast
agents) or for the treatment of non-autoimmune conditions (for example, delayed
hypersensitivity reactions caused by contact allergens) 13. There is a history of
interstitial lung disease or non-infectious pneumonia
Any serious chronic infection or active infection (excluding viral hepatitis) that
requires systemic antibacterial, antifungal or antiviral therapy (such as tuberculosis)
before starting treatment
The electrocardiogram during screening showed that the QT interval (QTc) corrected
according to the heart rate (corrected according to the Fridericia method) exceeded 450
msec
Note: If any patient finds that the QTc interval exceeds 450 msec during the first ECG
examination, the ECG will be repeated to confirm the result
Any of the following cardiovascular risk factors: Cardiogenic chest pain in the 28 days
before treatment, defined as moderate pain that restricts daily activities (ADL)
Symptomatic pulmonary embolism occurred within 28 days before treatment A history of acute
myocardial infarction occurred within 6 months before treatment
Any history of heart failure reaching New York Heart Association grade III or IV within 6
months of treatment Ventricular arrhythmia of grade ≥2 occurred within 6 months before
treatment Cerebrovascular accident (CVA) or transient ischemic attack (TIA) occurred within
months before treatment
Have received organ transplantation or hematopoietic stem cell transplantation (HSCT)
or any major surgery within 28 days before treatment
Known mental or substance abuse disorders that may interfere with test compliance
Live vaccine has been vaccinated 28 days before treatment. Note: Seasonal influenza
vaccines are generally inactivated influenza vaccines and are allowed to be used
Known history of human immunodeficiency virus infection (HIV) or syphilis infection
The history or evidence of any disease, treatment, or laboratory abnormality that may
confuse the test results, interfere with the participation of the subject during the entire
trial, or the main investigator believes that it does not meet the subject's best benefit
Currently participating in and receiving treatment, or participating in or
participating in other drug or device research within 4 weeks after the first
administration of the research drug
From the screening visit to 120 days after the last drug administration, pregnancy or
breastfeeding, or expectation of pregnancy or childbirth within the planned duration of the
trial
The investigator judges that the compliance is not good, or there are other conditions
that make the patients unsuitable to participate in this trial
There are various medical contraindications that prevent the use of enhanced imaging
(CT or MRI)
There are surgical contraindications, and the researchers believe that it is not
suitable for surgical patients
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