Anlotinib Plus Nab-Paclitaxels and S-1 for Patients with Advanced Biliary Tract Cancer As Second-Line Treatment

October 27, 2024 updated by: Ming Kuang, Sun Yat-sen University

Anlotinib Plus Nab-Paclitaxels and S-1 Versus FOLFOX for Patients with Advanced Biliary Tract Cancer As Second-Line Treatment: a Phase 2/3, Multi-centric Double-stage Randomized Controlled Trial

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Estimated)

206

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510080
        • The First Affiliated Hospital of Sun Yat-sen University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental
Experimental treatment under study
Drug: Albumin-bound Paclitaxel + Tegafur Gimeracil Oteracil (S-1) + Anlotinib
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
Active Comparator: Control
Standard of care second-line treatment for advanced biliary tract cancer
Drug: Oxaliplatin + Leucovorin + Fluorouracil (FOLFOX regimen)
Oxaliplatin 85 mg/m2,d1,iv.drip,Q2W + Leucovorin 400mg/m2,d1,iv.drip,Q2W+ Fluorouracil 2400 mg/m2 civ46h, Q2W

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: From randomisation to death, up to 5 years
Overall Survival (OS), defined as the time between the date of the subject's first dose and the subject's death from all causes. The OS of subjects who were alive at the time of the final follow-up visit was counted as data censored at the time of the final follow-up visit.
From randomisation to death, up to 5 years
Progression-Free Survival
Time Frame: From randomisation to disease progression or death, up to 5 years
Progression-Free Survival (PFS) is defined as the time from the date of the subject's first dose of medication to the date of the first documented tumor progression (assessed according toRECIST 1.1 criteria, with or without continuation of treatment) or the date of death from anycause, whichever occurs first. The median PFS and its 95% Cl will be analyzed using the Kaplan-Meier method and survival graphs will be plotted.
From randomisation to disease progression or death, up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate
Time Frame: From randomisation, up to 5 years
Refers to the proportion of patients whose tumors shrank by a certain amount and remained sofor a certain period of time, and includes both CR and PR cases. Objective tumor remission was assessed using the Solid Tumor Remission Assessment Criteria (RECIST 1.1 criteria).
From randomisation, up to 5 years
Disease control rate
Time Frame: From randomisation, up to 5 years
Refers to the proportion of patients whose tumors shrank by a certain amount and remained sofor a certain period of time, and includes both CR and PR cases. Obiective tumor remission was assessed using the Solid Tumor Remission Assessment Criteria (RECIST 1.1 criterial
From randomisation, up to 5 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quality of Life
Time Frame: From baseline, every 3weeks until end of treatment, an average of 4-6 months
Patients' quality of life was assessed according to the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30), assessed at baseline and every 3 weeks thereafter
From baseline, every 3weeks until end of treatment, an average of 4-6 months
Adverse Events
Time Frame: From randomisation, up to 5 years
Defined as the proportion of grade ≥3 hematologic or non-hematologic toxic events occurring from the start of medication to the end of follow-up. Adverse events include, but are not limited to, liver dysfunction, hematologic system damage, pulmonary toxicity, and ocular toxicity. The severity of adverse events will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0).
From randomisation, up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-sen University

Collaborators

CTTQ Pharma

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

November 25, 2024

Primary Completion (Estimated)

September 1, 2029

Study Completion (Estimated)

September 1, 2029

Study Registration Dates

First Submitted

October 27, 2024

First Submitted That Met QC Criteria

October 27, 2024

First Posted (Actual)

October 29, 2024

Study Record Updates

Last Update Posted (Actual)

October 29, 2024

Last Update Submitted That Met QC Criteria

October 27, 2024

Last Verified

October 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IIT-2024-658

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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