Trial Title:
Pembrolizumab With or Without Lenvatinib or Chemotherapy in First-Line Treatment of Advanced Biliary Tract Cancer
NCT ID:
NCT06230471
Condition:
Biliary Tract Neoplasms Immunotherapy
Conditions: Official terms:
Biliary Tract Neoplasms
Gemcitabine
Pembrolizumab
Oxaliplatin
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:
Pembrolizumab,Lenvatinib and Gemox Chemotherapy（Gemcitabine and Oxaliplatin）
Description:
Drug: Pembrolizumab Pembrolizumab 200 mg will be administered intravenously once every
three weeks, with intravenous infusion on Day 1 of each cycle. Drug: Lenvatinib Oral
Product The dose of lenvatinib is 12mg/day for patients with a body weight of ≥60 kg, and
8mg/day for patients with a body weight of <60 kg, taken once daily. Drug: Chemotherapy
GEMOX regimen: Gemcitabine 1000mg/m2 will be administered intravenously over 30 minutes
on Day 1 and Day 8; Oxaliplatin 100mg/m2 will be administered intravenously over 2 hours
on Day 1, and the cycle will be repeated every 3 weeks.
Arm group label:
Pembrolizumab,Lenvatinib and Gemox Chemotherapy（Gemcitabine and Oxaliplatin）
Intervention type:
Drug
Intervention name:
Pembrolizumab and Lenvatinib
Description:
Pembrolizumab and Lenvatinib
Arm group label:
Pembrolizumab and Lenvatinib
Intervention type:
Drug
Intervention name:
Pembrolizumab and Gemox Chemotherapy（Gemcitabine and Oxaliplatin）
Description:
Pembrolizumab and Gemox Chemotherapy（Gemcitabine and Oxaliplatin）
Arm group label:
Pembrolizumab and Gemox Chemotherapy（Gemcitabine and Oxaliplatin）
Summary:
Explore the impact of the first-line application of Pembrolizumab with or without
Lenvatinib or chemotherapy, on the survival, disease progression, and drug safety of
patients with advanced biliary tract cancers
Detailed description:
This trial is a three-arm, randomized, multi-center clinical study. Eligible subjects who
meet the study criteria will be screened and randomized in a 1:1:1 ratio to receive
treatment with intravenous infusion of Pembrolizumab with or without chemotherapy and
oral lenvatinib. The investigators will closely follow up and assess the efficacy and
safety of the combined treatment, evaluate the progression-free survival of the subjects
until progression occurs, and observe their overall survival as a secondary outcome.
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:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Chinese Academy of Medical Sciences & Peking Union Medical College Hospital (CAMS&PUMCH)
Address:
City:
Beijing
Zip:
100730
Country:
China
Status:
Recruiting
Contact:
Last name:
Haitao Zhao, Professor
Phone:
+861069156042
Email:
zhaoht@pumch.cn
Start date:
January 9, 2024
Completion date:
December 31, 2025
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/NCT06230471
