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

NCT06662877 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: IIT-2024-658
• Study Type: interventional
• Target: 206
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Biliary Tract Cancer; Second Line Treatment; Chemotherapy; Tyrosine Kinase Inhibitor

Keywords

biliary tract cancer; second-line treatment; Nab-Paclitaxels; S-1; Anlotinib; FOLFOX

Outcome Measures

Primary Outcomes (2)

• Overall Survival

  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

  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 Outcomes (2)

• Objective Response Rate

  From randomisation, up to 5 years

• Disease control rate

  From randomisation, up to 5 years

Other Outcomes (2)

• Quality of Life

  From baseline, every 3weeks until end of treatment, an average of 4-6 months

• Adverse Events

  From randomisation, up to 5 years

Study Arms (2)

Experimental

EXPERIMENTAL

Experimental treatment under study

Drug: Albumin-bound Paclitaxel + Tegafur Gimeracil Oteracil (S-1) + Anlotinib

Control

ACTIVE COMPARATOR

Standard of care second-line treatment for advanced biliary tract cancer

Drug: Oxaliplatin + Leucovorin + Fluorouracil (FOLFOX regimen)

Interventions

Albumin-bound Paclitaxel + Tegafur Gimeracil Oteracil (S-1) + Anlotinib DRUG

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

Experimental

Oxaliplatin + Leucovorin + Fluorouracil (FOLFOX regimen) DRUG

Oxaliplatin 85 mg/m2,d1,iv.drip,Q2W + Leucovorin 400mg/m2,d1,iv.drip,Q2W+ Fluorouracil 2400 mg/m2 civ46h, Q2W

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed a written informed consent form before enrollment;
• Age \>18 years, both male and female are eligible;
• Patients with pathologically confirmed advanced biliary tract that has progressed after first-line gemcitabine-based therapy;
• 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);
• ECOG Performance Status (PS) score: 0-1;
• Expected survival time longer than 12 weeks;
• 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;
• 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;
• The subject voluntarily participates in this study, has good compliance, and is willing to cooperate with safety and survival follow-ups.

You may not qualify if:

• Subjects with a history of or concurrent malignancies, except for cured basal cell carcinoma of the skin or carcinoma in situ of the cervix;
• Known allergy to macromolecular protein preparations or known hypersensitivity to the components of the administered drugs;
• Subjects with existing thyroid dysfunction that cannot be maintained within the normal range by medication;
• Uncontrolled hypertension despite optimal treatment, defined as systolic blood pressure \>150 mmHg or diastolic blood pressure \>90 mmHg;
• 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;
• Subjects with any active autoimmune disease or a history of autoimmune disease;
• 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;
• Subjects with central nervous system metastases;
• 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);
• Subjects with significant hemoptysis (fresh blood) within 2 months before enrollment or daily hemoptysis volume ≥2.5 ml;
• 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;
• Subjects with a history or current evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis, or severely impaired lung function;
• 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;
• Subjects who have received or may receive a live vaccine within 4 weeks before or during the study;
• Subjects with a known history of psychiatric drug abuse, alcoholism, or drug addiction;

Sponsors & Collaborators

• Sun Yat-sen University: lead
• CTTQ Pharma: collaborator

Study Sites (1)

The First Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, 510080, China

Location

Related Publications (12)

• Zhang W, Sun Y, Jiang Z, Qu W, Gong C, Zhou A. Nab-paclitaxel plus tegafur gimeracil oteracil potassium capsule (S-1) as first-line treatment for advanced biliary tract adenocarcinoma: a phase 2 clinical trial. Hepatobiliary Surg Nutr. 2023 Feb 28;12(1):37-44. doi: 10.21037/hbsn-21-172. Epub 2021 Oct 18.

  PMID: 36860259 BACKGROUND

• Shen G, Zheng F, Ren D, Du F, Dong Q, Wang Z, Zhao F, Ahmad R, Zhao J. Anlotinib: a novel multi-targeting tyrosine kinase inhibitor in clinical development. J Hematol Oncol. 2018 Sep 19;11(1):120. doi: 10.1186/s13045-018-0664-7.

  PMID: 30231931 BACKGROUND

• Klein O, Kee D, Nagrial A, Markman B, Underhill C, Michael M, Jackett L, Lum C, Behren A, Palmer J, Tebbutt NC, Carlino MS, Cebon J. Evaluation of Combination Nivolumab and Ipilimumab Immunotherapy in Patients With Advanced Biliary Tract Cancers: Subgroup Analysis of a Phase 2 Nonrandomized Clinical Trial. JAMA Oncol. 2020 Sep 1;6(9):1405-1409. doi: 10.1001/jamaoncol.2020.2814.

  PMID: 32729929 BACKGROUND

• Li X, Zhou N, Yang Y, Lu Z, Gou H. Efficacy and biomarker analysis of second-line nab-paclitaxel plus sintilimab in patients with advanced biliary tract cancer. Cancer Sci. 2024 Jul;115(7):2371-2383. doi: 10.1111/cas.16179. Epub 2024 Apr 18.

  PMID: 38638055 BACKGROUND

• Lim SH, Hong JY, Park JO, Park YS, Kim ST. Pemetrexed and Erlotinib as a Salvage Treatment in Patients With Metastatic Biliary Tract Cancer Who Failed Gemcitabine-containing Chemotherapy: A Phase II Single-arm Prospective Study. Anticancer Res. 2023 Sep;43(9):4161-4167. doi: 10.21873/anticanres.16607.

  PMID: 37648323 BACKGROUND

• Abou-Alfa GK, Macarulla T, Javle MM, Kelley RK, Lubner SJ, Adeva J, Cleary JM, Catenacci DV, Borad MJ, Bridgewater J, Harris WP, Murphy AG, Oh DY, Whisenant J, Lowery MA, Goyal L, Shroff RT, El-Khoueiry AB, Fan B, Wu B, Chamberlain CX, Jiang L, Gliser C, Pandya SS, Valle JW, Zhu AX. Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020 Jun;21(6):796-807. doi: 10.1016/S1470-2045(20)30157-1. Epub 2020 May 13.

  PMID: 32416072 BACKGROUND

• Merters J, Lamarca A. Integrating cytotoxic, targeted and immune therapies for cholangiocarcinoma. J Hepatol. 2023 Mar;78(3):652-657. doi: 10.1016/j.jhep.2022.11.005. Epub 2022 Nov 15.

  PMID: 36400328 BACKGROUND

• Yoo C, Kim KP, Jeong JH, Kim I, Kang MJ, Cheon J, Kang BW, Ryu H, Lee JS, Kim KW, Abou-Alfa GK, Ryoo BY. Liposomal irinotecan plus fluorouracil and leucovorin versus fluorouracil and leucovorin for metastatic biliary tract cancer after progression on gemcitabine plus cisplatin (NIFTY): a multicentre, open-label, randomised, phase 2b study. Lancet Oncol. 2021 Nov;22(11):1560-1572. doi: 10.1016/S1470-2045(21)00486-1. Epub 2021 Oct 14.

  PMID: 34656226 BACKGROUND

• Lamarca A, Palmer DH, Wasan HS, Ross PJ, Ma YT, Arora A, Falk S, Gillmore R, Wadsley J, Patel K, Anthoney A, Maraveyas A, Iveson T, Waters JS, Hobbs C, Barber S, Ryder WD, Ramage J, Davies LM, Bridgewater JA, Valle JW; Advanced Biliary Cancer Working Group. Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial. Lancet Oncol. 2021 May;22(5):690-701. doi: 10.1016/S1470-2045(21)00027-9. Epub 2021 Mar 30.

  PMID: 33798493 BACKGROUND

• Lamarca A, Hubner RA, David Ryder W, Valle JW. Second-line chemotherapy in advanced biliary cancer: a systematic review. Ann Oncol. 2014 Dec;25(12):2328-2338. doi: 10.1093/annonc/mdu162. Epub 2014 Apr 25.

  PMID: 24769639 BACKGROUND

• Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J; ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010 Apr 8;362(14):1273-81. doi: 10.1056/NEJMoa0908721.

  PMID: 20375404 BACKGROUND

• Ilyas SI, Affo S, Goyal L, Lamarca A, Sapisochin G, Yang JD, Gores GJ. Cholangiocarcinoma - novel biological insights and therapeutic strategies. Nat Rev Clin Oncol. 2023 Jul;20(7):470-486. doi: 10.1038/s41571-023-00770-1. Epub 2023 May 15.

  PMID: 37188899 BACKGROUND

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

Albumin-Bound Paclitaxel; tegafur-gimeracil-oteracil; S 1 (combination); anlotinib; Oxaliplatin; Leucovorin; Fluorouracil; Folfox protocol

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Coordination Complexes; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Central Study Contacts

Ming Kuang, MD, PhD

CONTACT

+86-020-87755766; kuangm@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice President, The First Affiliated Hospital, Sun Yat-sen University

Study Record Dates

• First Submitted: October 27, 2024
• First Posted: October 29, 2024
• Study Start: November 25, 2024
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2029
• Last Updated: October 29, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)