Trial Title:
Anlotinib Plus Nab-Paclitaxels and S-1 for Patients with Advanced Biliary Tract Cancer As Second-Line Treatment
NCT ID:
NCT06662877
Condition:
Biliary Tract Cancer
Second Line Treatment
Chemotherapy
Tyrosine Kinase Inhibitor
Conditions: Official terms:
Biliary Tract Neoplasms
Leucovorin
Paclitaxel
Oxaliplatin
Fluorouracil
Albumin-Bound Paclitaxel
Tegafur
Conditions: Keywords:
biliary tract cancer
second-line treatment
Nab-Paclitaxels
S-1
Anlotinib
FOLFOX
Study type:
Interventional
Study phase:
Phase 2/Phase 3
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Albumin-bound Paclitaxel + Tegafur Gimeracil Oteracil (S-1) + Anlotinib
Description:
Albumin-bound Paclitaxel, 125mg/m2,iv.drip,d1,d8,Q3W +Tegafur Gimeracil Oteracil (S-1)
40-60mg,p.o,bid,d1-d14,Q3W+Anlotinib 10mg,p.o,d1-d14,Q3W
Arm group label:
Experimental
Intervention type:
Drug
Intervention name:
Oxaliplatin + Leucovorin + Fluorouracil (FOLFOX regimen)
Description:
Oxaliplatin 85 mg/m2,d1,iv.drip,Q2W + Leucovorin 400mg/m2,d1,iv.drip,Q2W+ Fluorouracil
2400 mg/m2 civ46h, Q2W
Arm group label:
Control
Summary:
Biliary tract cancer (BTC) presents with a 5-year survival rate less than 5%. The goal of
this clinical trial is to evaluate if Anlotinib plus Nab-Paclitaxels and S-1 as
second-line regimen can improve the treatment efficacy in advanced biliary tract cancer
(BTC) after progression upon first-line standard treatment, in comparison with standard
second-line FOLFOX regimen.
Detailed description:
Biliary tract cancer (BTC) mainly includes intrahepatic cholangiocarcinoma, hilar
cholangiocarcinoma, extrahepatic cholangiocarcinoma and gallbladder carcinoma, and the
5-year survival rate is less than 5%. Most patients were diagnosed as advanced stage, and
missed the opportunity of radical surgery. ABC-02 study established gemcitabine combined
with platinum drugs as the first-line standard treatment for unresectable BTC. However,
after the disease progresses, the second-line treatment options and efficacies are
limited. In recent years, BTC second-line treatment has made some breakthroughs in the
field of chemotherapy and targeted therapy. However, the benefits of chemotherapy,
immunotherapy and targeted drugs alone in the second line treatment of BTC is
unsatisfactory. The combined scheme of two or three drugs sees the possibility of
patients benefiting, but it still needs better scheme design and larger sample size for
further verification. A phase II single-arm small-sample clinical trial exploring
albumin-bound paclitaxel combined with S-1 capsule in the first-line treatment of
advanced biliary adenocarcinoma initially showed the efficacy and safety of AS regimen in
cholangiocarcinoma, and the efficacy and safety of Anlotinib in BTC were also confirmed
in the small-sample study. Therefore, this study intends to explore the efficacy and
safety of the second-line treatment of advanced BTC with Anlotinib combined with AS
chemotherapy in comparison with the establised standard second-line regimen (FOLFOX).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Signed a written informed consent form before enrollment;
2. Age >18 years, both male and female are eligible;
3. Patients with pathologically confirmed advanced biliary tract that has progressed
after first-line gemcitabine-based therapy;
4. Have measurable lesions (according to RECIST 1.1 criteria, non-lymph node lesions
with a long diameter ≥10 mm on CT scan, or lymph node lesions with a short diameter
≥15 mm on CT scan);
5. ECOG Performance Status (PS) score: 0-1;
6. Expected survival time longer than 12 weeks;
7. Key organ functions meet the following criteria (without the use of any blood
components or growth factors within 14 days): Hematology: Neutrophils ≥1.5×10⁹/L;
Platelet count ≥100×10⁹/L; Hemoglobin ≥ 90 g/L; Liver and kidney function: Serum
creatinine (SCr) ≤ 1.5 times the upper limit of normal (ULN) or creatinine clearance
rate ≥50 ml/min (Cockcroft-Gault formula); Total bilirubin (TBIL) ≤ 1.5 times the
ULN; Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels ≤ 2.5
times the ULN (if abnormal liver function is due to liver metastasis, then ≤ 5 times
the ULN); urine protein < 2+; if urine protein ≥ 2+, 24-hour urine protein
quantification must show protein ≤1g;
8. Normal coagulation function, no active bleeding or thrombotic diseases:
International Normalized Ratio (INR) ≤ 1.5 × ULN; Activated Partial Thromboplastin
Time (APTT) ≤ 1.5 × ULN; Prothrombin Time (PT) ≤ 1.5 × ULN;
9. The subject voluntarily participates in this study, has good compliance, and is
willing to cooperate with safety and survival follow-ups.
Exclusion Criteria:
1. Subjects with a history of or concurrent malignancies, except for cured basal cell
carcinoma of the skin or carcinoma in situ of the cervix;
2. Known allergy to macromolecular protein preparations or known hypersensitivity to
the components of the administered drugs;
3. Subjects with existing thyroid dysfunction that cannot be maintained within the
normal range by medication;
4. Uncontrolled hypertension despite optimal treatment, defined as systolic blood
pressure >150 mmHg or diastolic blood pressure >90 mmHg;
5. Subjects with uncontrolled cardiac clinical symptoms or diseases, such as: (1) heart
failure above NYHA class II, (2) unstable angina, (3) myocardial infarction within
the past year, (4) clinically significant supraventricular or ventricular
arrhythmias requiring treatment or intervention;
6. Subjects with any active autoimmune disease or a history of autoimmune disease;
7. Subjects using immunosuppressive agents or systemic or absorbable local
corticosteroids for immunosuppressive purposes (prednisone dose >10 mg/day or
equivalent efficacy corticosteroids) who continue to use them within 2 weeks before
enrollment;
8. Subjects with central nervous system metastases;
9. Subjects with active infections or unexplained fever >38.5°C during screening or
before the first dose (subjects with tumor-related fever, as judged by the
investigator, may be enrolled);
10. Subjects with significant hemoptysis (fresh blood) within 2 months before enrollment
or daily hemoptysis volume ≥2.5 ml;
11. Subjects with any condition that may increase the risk of gastrointestinal bleeding
or perforation, such as active peptic ulcers, known intraluminal metastatic lesions,
inflammatory bowel disease, history of abdominal fistula, gastrointestinal
perforation, or intra-abdominal abscess within 28 days before the start of the
study;
12. Subjects with a history or current evidence of pulmonary fibrosis, interstitial
pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis, or
severely impaired lung function;
13. Subjects with a history or current evidence of bronchiectasis, cavitary pulmonary
tuberculosis, lung abscess, rheumatic heart disease with mitral valve stenosis, or
cardiogenic pulmonary edema, which could cause hemoptysis;
14. Subjects with congenital or acquired immune deficiencies, such as those infected
with HIV or with active hepatitis (transaminase levels not meeting inclusion
criteria, hepatitis B reference: HBV DNA ≥1000 IU/ml; hepatitis C reference: HCV RNA
≥1000 IU/ml);
15. Subjects who have received or may receive a live vaccine within 4 weeks before or
during the study;
16. Subjects with a known history of psychiatric drug abuse, alcoholism, or drug
addiction;
17. Pregnant or breastfeeding women or those planning to conceive during the study
period;
18. Subjects whom the investigator deems should be excluded from the study, such as
those with factors that may lead to early termination of the study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
The First Affiliated Hospital of Sun Yat-sen University
Address:
City:
Guangzhou
Zip:
510080
Country:
China
Contact:
Last name:
Ming Kuang, MD, PhD
Phone:
+86-020-87755766
Email:
kuangm@mail.sysu.edu.cn
Start date:
November 25, 2024
Completion date:
September 1, 2029
Lead sponsor:
Agency:
Sun Yat-sen University
Agency class:
Other
Collaborator:
Agency:
CTTQ Pharma
Agency class:
Other
Source:
Sun Yat-sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06662877
