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Biliary Tract CancerPhase 2/3NCT06662877

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

A Phase 2/3 study testing Albumin-bound Paclitaxel + Tegafur Gimeracil Oteracil (S-1) + Anlotinib and Oxaliplatin + Leucovorin + Fluorouracil (FOLFOX regimen) in people with Biliary Tract Cancer and Second Line Treatment, run by Sun Yat-sen University at 1 site in China.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Albumin-bound Paclitaxel + Tegafur Gimeracil Oteracil (S-1) + Anlotinib and Oxaliplatin + Leucovorin + Fluorouracil (FOLFOX regimen)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
206 participants
Where
1 siteChina
Study dates
25 Nov 2024to 1 Sep 2029
Phase
Phase 2/3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
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  • 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.

Who cannot join

  • 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;
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  • 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 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);
  • 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;
  • Pregnant or breastfeeding women or those planning to conceive during the study period;
  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Ming Kuang, MD, PhD contact

+86-020-87755766

kuangm@mail.sysu.edu.cn

China1 site

  • The First Affiliated Hospital of Sun Yat-sen University

    Guangzhou, Guangdong, 510080

    Ming Kuang, MD, PhD, +86-020-87755766, kuangm@mail.sysu.edu.cn

Other trials in China

About this study

Official title: 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.

Read the 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).

Being tested
Albumin-bound Paclitaxel + Tegafur Gimeracil Oteracil (S-1) + Anlotinib, Oxaliplatin + Leucovorin + Fluorouracil (FOLFOX regimen)
Keywords
biliary tract cancer, second-line treatment, Nab-Paclitaxels, S-1, Anlotinib, FOLFOX
Medical subject headings
Biliary Tract Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Albumin-bound Paclitaxel + Tegafur Gimeracil Oteracil (S-1) + AnlotinibDrug

    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

  • 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

Study groups in NCT06662877
Study groupRoleWhat they receive
ExperimentalExperimentalExperimental treatment under study
Receives: Drug: Albumin-bound Paclitaxel + Tegafur Gimeracil Oteracil (S-1) + Anlotinib
ControlActive comparatorStandard of care second-line treatment for advanced biliary tract cancer
Receives: Drug: Oxaliplatin + Leucovorin + Fluorouracil (FOLFOX regimen)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: From randomisation to death, up to 5 years

  2. 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.

    Measured: From randomisation to disease progression or death, up to 5 years

Secondary outcomes (2)

  1. Objective Response Rate

    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).

    Measured: From randomisation, up to 5 years

  2. Disease control rate

    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

    Measured: From randomisation, up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Oct 2024
  2. Study start25 Nov 2024 (estimated)
  3. Primary completion1 Sep 2029 (estimated)
  4. Study completion1 Sep 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
206 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06662877
Sponsor's protocol ID
IIT-2024-658
Status last verified
Oct 2024
First submitted
27 Oct 2024
Last updated
29 Oct 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 36860259

  • 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.

    PubMed 30231931

  • 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.

    PubMed 32729929

  • 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.

    PubMed 38638055

  • 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.

    PubMed 37648323

  • 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.

    PubMed 32416072

  • 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.

    PubMed 36400328

  • 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.

    PubMed 34656226

  • 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.

    PubMed 33798493

  • 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.

    PubMed 24769639

  • 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.

    PubMed 20375404

  • 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.

    PubMed 37188899

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Albumin-bound Paclitaxel + Tegafur Gimeracil Oteracil (S-1) + Anlotinib and Oxaliplatin + Leucovorin + Fluorouracil (FOLFOX regimen) in people with Biliary Tract Cancer and Second Line Treatment, run by Sun Yat-sen University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 29 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Ming Kuang, MD, PhD (+86-020-87755766, kuangm@mail.sysu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (time frame: From randomisation to death, up to 5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06662877, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2024; AzTrials last refreshed its copy on 26 Oct 2026.

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