Trial Title:
Toripalimab With or Without Lenvatinib or Chemotherapy in First-Line Treatment of Advanced Biliary Tract Cancer
NCT ID:
NCT06362317
Condition:
Biliary Tract Neoplasms Immunotherapy
Conditions: Official terms:
Biliary Tract Neoplasms
Lenvatinib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Toripalimab
Description:
Toripalimab 240mg, intravenous infusion every 3 weeks until disease progression or
occurrence of intolerable toxicity.
Arm group label:
Toripalimab and Gemox Chemotherapy（Gemox or GC）
Arm group label:
Toripalimab and Lenvatinib
Arm group label:
Toripalimab, Lenvatinib and Gemox Chemotherapy（Gemox or GC）
Intervention type:
Drug
Intervention name:
Lenvatinib
Description:
When the body weight is ≥60 kg, the dosage of Lenvatinib is 12mg qd, when body weight <
60kg the dosage is 8mg qd.
Arm group label:
Toripalimab and Lenvatinib
Arm group label:
Toripalimab, Lenvatinib and Gemox Chemotherapy（Gemox or GC）
Intervention type:
Drug
Intervention name:
Gemox Chemotherapy（Gemox or GC）
Description:
Chemotherapy drugs: GC regimen is preferred, and if patients cannot tolerate it, GEMOX
regimen is used.
Gemcitabine + oxaliplatin (GEMOX) regimen chemotherapy: every 21 days (3 weeks), 1000
mg/m2 of gemcitabine was administered intravenously for more than 30 min on the 1st and
8th day, and 100 mg/m2 of oxaliplatin was administered intravenously for 2h on the 1st
day Gemcitabine + cisplatin (GC) regimen chemotherapy: 1250 mg/m2 was administered
intravenously for 30 min on day 1 and day 8, respectively, and 100 mg/m2 was administered
intravenously for 2 hours after gemcitabine treatment on day 1.
Arm group label:
Toripalimab and Gemox Chemotherapy（Gemox or GC）
Arm group label:
Toripalimab, Lenvatinib and Gemox Chemotherapy（Gemox or GC）
Summary:
Explore the impact of the first-line application of Toripalimab with or without
Lenvatinib or chemotherapy, on the survival, disease progression, and drug safety of
patients with advanced biliary tract cancers
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- The subjects voluntarily participate in the study and agree to sign the informed
consent form, are compliant, and cooperate with follow-up.
They are over 18 years of age and gender is not restricted when signing the informed
consent form.
They have histologically confirmed unresectable advanced or metastatic biliary tract
adenocarcinoma, including intrahepatic or extrahepatic cholangiocarcinoma and gallbladder
cancer.
Patients who are diagnosed with unresectable or metastatic disease and have not received
prior treatment are eligible for inclusion.
Patients who have undergone curative surgery and experienced disease recurrence after
more than 6 months; or patients who have completed adjuvant therapy (chemotherapy and/or
radiotherapy) and have been disease-free for more than 6 months after completing adjuvant
therapy are eligible for inclusion.
They have at least one measurable lesion (as defined by RECIST 1.1, the measurable lesion
is a spiral CT scan long diameter ≥10mm or lymph node short diameter ≥15mm).
Their ECOG score is 0-1 in the week prior to enrollment.
Based on the investigator's assessment, their estimated survival time is ≥3 months.
Patients with active hepatitis B or C require relevant antiviral treatment, with HBV-DNA
<2000 IU/ml (<104 copies/ml), and have received at least 14 days of antiviral treatment
before participating in the study. HCV RNA-positive patients must follow local standard
treatment guidelines for antiviral therapy, and their liver function is within CTCAE
Grade 1 elevation.
Their hematological and organ functions are adequate, based on laboratory test results
obtained within 14 days before the start of the study (unless otherwise specified):
Hematology: (no blood transfusion, no G-CSF, no drug correction within 14 days prior to
screening) Hb ≥90 g/L; neutrophil count ≥1.5×109/L; PLT≥100×109/L.
Biochemistry: (no albumin transfusion within 14 days) Appropriate liver function: ALT and
AST ≤2.5×ULN; for patients with liver metastases, ALT and AST ≤5 × ULN. Serum bilirubin
≤2.0×ULN; these conditions do not apply to patients with confirmed Gilbert's syndrome.
Any clinically significant biliary obstruction should be resolved before randomization.
Appropriate renal function: creatinine ≤1.5×ULN, or creatinine clearance rate (CCr)
>50mL/min (using the standard Cockcroft-Gault formula): Female: CrCl = ((140 - age) x
weight (kg) x 0.85) / 72 x serum creatinine (mg/ dL) Male: CrCl = ((140 - age) x weight
(kg) x 1.00) / 72 x serum creatinine (mg/ dL)
Women of childbearing potential: agree to abstain from sexual intercourse or use
contraceptive methods with a failure rate of less than 1% during the treatment period and
for at least 6 months after the last dose. If a female patient has menstruation and has
not reached menopause (continuous absence of menstruation for ≥12 months without other
reasons), and has not undergone sterilization surgery (removal of ovaries and/or uterus),
she is considered to be of childbearing potential. Examples of contraceptive methods with
a failure rate of less than 1% include bilateral tubal ligation, male sterilization,
hormone-based contraceptives that inhibit ovulation, hormone-releasing intrauterine
devices, and copper intrauterine devices. The reliability of sexual restraint should be
evaluated relative to the duration of the clinical trial and the patient's preferred
lifestyle and daily routine. Periodic abstinence (such as calendar day, ovulation period,
symptom temperature, or post-ovulation method) and ejaculation outside the vagina are
unacceptable contraceptive methods.
Male: agree to abstain from sexual intercourse or use contraceptive measures, agree not
to donate sperm, as defined below: When the female partner is of childbearing potential,
male patients must abstain during the treatment period and for 6 months after the last
dose, or use a condom plus other contraceptive methods to achieve a failure rate of less
than 1%. Male patients must also agree not to donate sperm during the same period. When
the female partner is already pregnant, male patients must abstain or use a condom to
prevent fetal exposure to the study during the treatment period and for 6 months after
the last dose. The reliability of sexual restraint should be evaluated relative to the
duration of the clinical trial and the patient's preferred lifestyle and daily routine.
Periodic abstinence (such as calendar day, ovulation period, symptom temperature, or
post-ovulation method) and ejaculation outside the vagina are unacceptable contraceptive
methods.
Exclusion Criteria:
- Previous systemic treatment received.
ECOG score > 1. Pancreatic cancer. Pregnant (positive pregnancy test before medication)
or breastfeeding women. Known allergy or intolerance to recombinant humanized PD-1
monoclonal antibody drugs, lenvatinib and its components (or any excipients).
Received local anti-tumor treatment within 4 weeks before the first study drug treatment,
including but not limited to surgery, radiotherapy, hepatic artery embolization, TACE,
hepatic artery infusion, radiofrequency ablation, cryoablation, or percutaneous ethanol
injection (allowing palliative radiotherapy for bone metastases at least 2 weeks before
study drug treatment).
Previous or existing grade 3 or higher gastrointestinal fistula or non gastrointestinal
fistula (such as skin) according to CTCAE 5.0 criteria.
Multiple factors affecting oral administration of lenvatinib (such as inability to
swallow, chronic diarrhea and intestinal obstruction, or other conditions that
significantly affect drug intake and absorption).
Major surgery (except biopsy) has been performed within 4 weeks before the first study
drug treatment, or the surgical incision has not completely healed; minor surgery (such
as simple excision, biopsy, etc.) was performed within 7 days before the first study
intervention.
Significant cardiovascular and cerebrovascular diseases, including but not limited to
acute myocardial infarction, severe/unstable angina pectoris, cerebrovascular accidents
or transient ischemic attacks within 6 months before enrollment, congestive heart failure
(New York Heart Association classification ≥2), arrhythmia requiring antiarrhythmic drugs
(except beta blockers or digoxin), and repeated electrocardiogram showing QTc interval
>480 milliseconds (ms). Hepatic or renal dysfunction, with manifestations such as
jaundice, ascites, and/ or bilirubin >3×ULN, creatinine ratio >3.5g/24 hours, or renal
failure requiring blood or peritoneal dialysis, and/or urinary routine showing urine
protein ≥++ or confirmed 24-hour urine protein quantification >1.0g.
Persistent infection > grade 2 (CTCAE 5.0). History of thrombotic events (including
stroke and/or transient ischemic attacks) within the past 6 months.
Poorly controlled hypertension (systolic blood pressure >160mmHg, diastolic blood
pressure >100mmHg) despite treatment with antihypertensive medications. Active autoimmune
disease or history of autoimmune disease within the past 2 years; participants with
active, known, or suspected autoimmune diseases that may affect important organ function
or require systemic immunosuppressive therapy are excluded, including but not limited to
myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus,
rheumatoid arthritis, antiphospholipid syndrome associated with thrombosis, Wegener's
granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis,
vasculitis, or glomerulonephritis. However, participants with type 1 diabetes,
hypothyroidism requiring only hormone replacement, skin diseases that do not require
systemic treatment (such as vitiligo, psoriasis, or alopecia) or participants who will
not relapse without external triggering factors are allowed.
Replacement therapy (such as thyroid hormone, insulin, or physiological corticosteroid
replacement therapy for adrenal or pituitary insufficiency) is not considered a form of
systemic treatment.
Known active central nervous system (CNS) metastasis and/or carcinomatous meningitis.
Participants with previously treated brain metastases may participate as long as they are
stable (evidence of no progression on imaging at least 4 weeks before the first trial
treatment and any neurological symptoms have returned to baseline), have no evidence of
new or enlarging brain metastases, and have not used steroids for at least 7 days before
trial treatment. This exception does not include carcinomatous meningitis, which is
excluded regardless of clinical stability. Participants with known or untreated brain
metastases or epilepsy requiring medication are also excluded. Planned or prior organ or
allogeneic bone marrow transplantation. Known history of active tuberculosis
(Mycobacterium tuberculosis). History of gastrointestinal bleeding within the past 6
months or clear evidence of gastrointestinal bleeding tendencies, such as bleeding
esophageal varices, locally active gastrointestinal ulcerative lesions, fecal occult
blood ≥(++), cannot be included; if fecal occult blood (+), gastroscopy is required;
evidence or history of bleeding mechanism disorders of grade ≥3 (CTCAE 5.0), or other
bleeding disorders.
Known human immunodeficiency virus (HIV) infection. Known active hepatitis B or C
infection and not receiving regular treatment. During the screening period, HBV DNA ≥2000
IU/ml (or ≥104 copies/ ml) must be reduced to <2000 IU/ml (or <104 copies/ml) with
entecavir before enrollment. For eligible participants with Anti-HBc (+)/HBsAg (+)/ HBV
DNA< 2000 IU/ml or Anti-HBc (+)/HBsAg (-)/HBV DNA< 2000 IU/ ml, antiviral therapy must be
administered during the trial period using the original medication or entecavir or
tenofovir.
Severe non-healing wounds, ulcers, or fractures. History of substance abuse or any
medical, psychological, or social condition that may affect the study, patient
compliance, or endanger patient safety.
Unresolved toxicity of grade >1 (CTCAE 5.0) caused by any prior treatment/procedure,
except for hair loss, anemia, and hypothyroidism.
Severe non-healing wounds, ulcers, or fractures. Objective evidence of severe pulmonary
impairment, such as a history of severe pulmonary fibrosis, interstitial pneumonia,
pneumoconiosis, radiation pneumonitis, or drug-related pneumonia.
Treatment with a strong CYP3A4 inhibitor (e.g., clarithromycin, indinavir, itraconazole,
lopinavir, nelfinavir, ritonavir, saquinavir, telaprevir, voriconazole, etc.) within 7
days before participating in the study, or treatment with a strong CYP3A4 inducer (e.g.,
phenytoin, phenobarbital, primidone, carbamazepine, rifampin, rifabutin, rifapentine, or
St. John's Wort) within 12 days before participating in the study.
Concomitant malignancy, except for previously treated skin basal cell carcinoma, squamous
cell carcinoma, carcinoma in situ of the breast or cervix, superficial bladder cancer
that has been treated, and prostate cancer that has been treated with surgery and has a
normal range of PSA tumor markers, or any other malignancy that has not been cured within
the past 5 years.
The investigator determines that the participant is unsuitable for the study based on
overall medical condition.
Concurrent participation in another clinical study.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Chinese Academy of Medical Sciences & Peking Union Medical College Hospital (CAMS&PUMCH)
Address:
City:
Beijing
Zip:
100005
Country:
China
Status:
Recruiting
Contact:
Last name:
Haitao Zhao, Professor
Phone:
+861069156042
Email:
zhaoht@pumch.cn
Start date:
March 6, 2024
Completion date:
March 6, 2026
Lead sponsor:
Agency:
Peking Union Medical College Hospital
Agency class:
Other
Source:
Peking Union Medical College Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06362317
