Trial Title:
Neoantigen Vaccine Plus Capecitabine as Adjuvant Therapy for Intrahepatic Cholangiocarcinoma After Radical Resection
NCT ID:
NCT06406816
Condition:
Intrahepatic Cholangiocarcinoma
Conditions: Official terms:
Cholangiocarcinoma
Capecitabine
Study type:
Interventional
Study phase:
Early Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Prevention
Masking:
None (Open Label)
Intervention:
Intervention type:
Combination Product
Intervention name:
Neoantigen Vaccine plus Capecitabine
Description:
1. Capecitabine.Twice a day, 30 minutes after breakfast, swallow with water, continue
for 2 weeks, then stop for 1 week, constitutes one cycle; three weeks make one
cycle, lasting for 8 cycles.
2. Neoantigen Vaccine . Every 3 weeks, once every 21 days, for 4 to 8 cycles. The
injection is administered on the first day after cessation of capecitabine.
Treatment can last for up to 6 months without occurrences such as the researcher
determining no further clinical benefit, intolerable toxic reactions, initiation of
new anti-tumor treatment, withdrawal of informed consent, loss to follow-up, death,
or other circumstances specified in the protocol that require treatment termination.
Arm group label:
Neoantigen Vaccine plus Capecitabine
Summary:
This study is a single-arm, open-label, exploratory clinical trial, with the primary
objective to evaluate the efficacy and safety of the Neoantigen Vaccine plus capecitabine
for the treatment of high-intermediate risk recurrent intrahepatic cholangiocarcinoma
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Sign a written informed consent form and be able to comply with the scheduled visits
and related procedures as per the protocol;
2. Age ≥18 years and ≤75 years, any gender;
3. Confirmed pathologically as a patient with intrahepatic cholangiocarcinoma;
4. Not receiving neoadjuvant therapy, underwent surgical resection, and pathology
confirmed high-risk factors for recurrence: positive margins, lymph node metastasis,
vascular invasion, nerve invasion, diameter >5cm, classified as stage IB-IIIB
according to AJCC TNM (8th edition, 2017), and have not yet received systemic
adjuvant therapy;
5. Child-Pugh score grade A;
6. ECOG score of 0-1;
7. If infected with hepatitis B virus (HBV), such as HBsAg positive, HBV-DNA must be
tested and HBV-DNA should be <2000 IU/mL (if the research center uses copy/mL as the
detection unit, then it must be <104 copy/mL), and must have received at least 1
week of anti-HBV treatment before the start of the study and willing to undergo
antiviral treatment throughout the study period; HCV RNA positive patients must
receive antiviral treatment according to the treatment guidelines;
8. The subjects are required to provide fresh or archived tumor tissue samples as
requested in the post-operative protocol for use in gene sequencing and peptide gel
vaccine preparation;
9. Expected survival period ≥12 weeks;
10. Has sufficient organ and bone marrow function, has not received blood transfusion or
hematopoietic growth factor within 14 days before screening. Laboratory test values
meet the following requirements, as follows: a. Hematology: Absolute neutrophil
count (ANC) ≥1.5×10^9/L; Platelet count (PLT) ≥50×10^9/L; Hemoglobin (HGB) ≥90g/L b.
Liver function: Total bilirubin (TBIL) ≤3×upper limit of normal value (ULN); Alanine
aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤5×ULN; Serum albumin
≥30g/L c. Renal function: Serum creatinine (Cr) ≤1.5×ULN, or for subjects with
creatinine >1.5×ULN, creatinine clearance rate (CCr) ≥45 mL/min (Cockcroft-Gault
formula); Urine routine results show urine protein <2+; For subjects with urine
protein ≥2+ on baseline urine routine testing, 24-hour urine collection should be
performed and 24-hour urine protein quantification <1 g d. Coagulation function:
International normalized ratio (INR) or APTT ≤1.5×ULN;
11. Fertile women: Must agree to abstain from sexual intercourse (avoid heterosexual
intercourse) or use a reliable and effective method of contraception from the start
of signing the informed consent form until at least 120 days after the last dose of
study drug. Serum HCG test must be negative in the week before treatment; and must
be non-lactating. If female patients have menstruated and have not reached
postmenopausal status (consecutive absence of menstruation for ≥12 months, no other
reason except for menopause), and have not undergone sterilization surgery (such as
hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), they are
considered fertile;
12. For male subjects with fertile female partners, must agree to abstain from sexual
intercourse or use a reliable and effective method of contraception from the start
of signing the informed consent form until at least 120 days after the last dose of
study drug. Male subjects must also agree not to donate sperm during the same
period. Male subjects whose partners are pregnant must use condoms, and no other
contraceptive method is necessary
Exclusion Criteria:
1. Pathological diagnosis of hepatocellular carcinoma, mixed hepatocellular carcinoma,
hilar cholangiocarcinoma, and gallbladder cancer;
2. Patients with other active malignant tumors other than intrahepatic
cholangiocarcinoma within 5 years or simultaneously. Patients with localized tumors
that have been cured, such as basal cell carcinoma of the skin, squamous cell
carcinoma of the skin, superficial bladder cancer, prostatic carcinoma in situ,
cervical carcinoma in situ, breast carcinoma in situ, etc., can be included;
3. Currently with interstitial pneumonia or interstitial lung disease, or with a
history of interstitial pneumonia or interstitial lung disease requiring steroid
treatment in the past, or other possible interferences with the judgment and
treatment of immune-related pulmonary toxicity, such as pulmonary fibrosis,
organizing pneumonia (e.g., obliterative bronchiolitis), pneumoconiosis,
drug-related pneumonia, idiopathic pneumonia, or subjects with active pneumonia or
severe lung function impairment shown by chest CT during screening; active
tuberculosis;
4. Presence of active autoimmune diseases or a history of autoimmune diseases that may
relapse [including but not limited to autoimmune hepatitis, interstitial pneumonia,
uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism,
hypothyroidism (patients controlled only by hormone replacement therapy can be
included)]; patients with skin diseases that do not require systemic treatment, such
as vitiligo, psoriasis, alopecia, controlled type 1 diabetes mellitus treated with
insulin, or patients with asthma who have completely resolved in childhood and
require no intervention as adults can be included; patients with asthma requiring
bronchodilators for medical intervention cannot be included;
5. Within 2 weeks before the start of the study, use of immunosuppressants or systemic
hormone therapy to achieve immunosuppression (dose >10mg/day prednisone or other
equivalent glucocorticoids);
6. Patients with active infections, with unexplained fever ≥38.5°C within 1 week before
the start of the study, or with a baseline white blood cell count >15×10^9/L;
7. Patients with congenital or acquired immune deficiency (e.g., HIV infection);
8. Within 4 weeks before the first dose, received or planned to receive live or
attenuated live vaccines during the study;
9. Within 6 months before the start of the study, significant clinical bleeding
symptoms or a clear bleeding tendency, such as gastrointestinal bleeding,
hemorrhagic gastric ulcer, or vasculitis, etc. If positive for occult blood in stool
at baseline, it can be retested; if still positive after retesting, endoscopy is
required;
10. Known existing hereditary or acquired bleeding disorders (e.g., hemophilia
patients), coagulation disorders, thrombocytopenia, etc.); currently receiving
full-dose oral or injected anticoagulants or thrombolytics for therapeutic purposes
(prophylactic use of low-dose aspirin is allowed, etc.);
11. Within 6 months before the start of the study, arterial thromboembolic events, such
as cerebrovascular accidents (including transient ischemic attacks, intracerebral
hemorrhage, cerebral infarction), CTCAE grade 3 or higher deep vein thrombosis,
pulmonary embolism, etc;
12. Uncontrolled heart clinical symptoms or diseases, such as: (1) New York Heart
Association (NYHA) standard II or higher heart failure or echocardiography: LVEF
(left ventricular ejection fraction) <50%; (2) unstable angina pectoris; (3)
myocardial infarction within 1 year before treatment; (4) clinically significant
supraventricular or ventricular arrhythmias requiring treatment or intervention; (5)
QTc >450ms (men); QTc >470ms (women) (QTc interval calculated using the Fridericia
formula: if QTc is abnormal, it can be continuously measured for 3 times at
intervals of 2 minutes and the average value is taken);
13. Hypertension that cannot be well controlled with antihypertensive medication
(systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg) (based on the
average of blood pressure readings from ≥2 measurements); previous history of
hypertensive emergencies or hypertensive encephalopathy is allowed;
14. Within 6 months before the start of the study, the occurrence of major vascular
diseases (e.g., aortic aneurysms requiring surgical repair or recent peripheral
arterial thrombosis);
15. Severe, unhealed, or open wounds, as well as active ulcerations or untreated
fractures;
16. Within 4 weeks before the start of the study, received major surgery treatment
(excluding diagnostic procedures) or expect to undergo major surgery during the
study period;
17. Unable to swallow pills, malabsorption syndrome, or any condition that affects
gastrointestinal absorption;
18. Within 6 months before the start of the study, experienced intestinal obstruction
and/or had clinical signs or symptoms of gastrointestinal obstruction, including
incomplete obstruction related to the original disease or requiring routine
parenteral hydration, parenteral nutrition, or tube feeding. If patients with
incomplete obstruction/obstruction syndrome/intestinal obstruction signs/symptoms at
the time of initial diagnosis received definitive (surgical) treatment to resolve
symptoms, they may be eligible for inclusion in the study;
19. Within 2 weeks before the start of the study, the use of strong CYP3A4/CYP2C1
inducers including rifampicin (and its analogues) and St. John's wort, or strong
CYP3A4/CYP2C19 inhibitors;
20. Subjects who have received other neoantigen vaccines, or are allergic to any
chemotherapy drugs, anti-angiogenic targeted drugs, or excipients
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Start date:
May 2024
Completion date:
May 2026
Lead sponsor:
Agency:
Yongyi Zeng
Agency class:
Other
Source:
Meng Chao Hepatobiliary Hospital of Fujian Medical University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06406816
