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Biliary Tract CancerPhase 2GENENCT07599995

Gemcitabine-Cisplatin Plus Envafolimab in Resectable Biliary Tract Malignancies

A Phase 2 study testing Neoadjuvant therapy followed by surgery in people with Biliary Tract Cancer, run by Sir Run Run Shaw Hospital.

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

This trial is to evaluate the efficacy of Gemcitabine-Cisplatin (GC) plus Envafolimab neoadjuvant therapy in the patients at high risk of recurrence. Primary endpoint: Major Pathologic Response (MPR). Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Biliary Tract Cancer
What is being tested?
Neoadjuvant therapy followed by surgery
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
No sites listed yet
Study dates
30 May 2026to 30 Mar 2030
Phase
Phase 2
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 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants who have signed a written Informed Consent Form (ICF);
  • Male or female participants aged 18-80 years;
  • Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0/1;
  • Biliary Tract Cancer (BTC) diagnosed by puncture pathology prior to enrollment;
  • Participants must meet the following requirements for major vital organ function: a. Absolute neutrophil count (ANC) ≥ 1.5×10⁹/L; platelet count ≥ 90×10⁹/L; hemoglobin ≥ 9 g/dL; b. Coagulation function: international normalized ratio (INR) ≤ 1.2; c. Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 3 times the upper limit of normal (ULN); d. Serum albumin ≥ 3.5 g/dL; total bilirubin ≤ 1.5 times the ULN. Patients with obstructive jaundice who meet the eligibility criteria after percutaneous transhepatic cholangial drainage or endoscopic retrograde cholangiopancreatography treatment are also eligible for enrollment; e. Child-Pugh class A or B; f. Serum creatinine ≤ 1.5 times the ULN;
  • Patients with high-risk factors for recurrence. The criteria are defined as meeting at least one of the following: a. Preoperative CA19-9 ≥ 200 U/mL; b. Tumor diameter ≥ 5 cm or multiple tumor nodules on imaging; c. Regional lymph node metastasis with a short-axis diameter ≥ 1.0 cm on imaging; d. Vascular invasion (portal vein or hepatic artery) on imaging; e. Low or undifferentiated histologic grade;
  • Participants who have at least 1 measurable lesion (RECIST v1.1);
  • Be able to provide fresh stool samples and liver samples if undergoing surgery.

Who cannot join

  • Pathological diagnosis of hepatocellular carcinoma, mixed hepatocellular carcinoma, and other non-cholangiocarcinoma malignant tumor components;
  • Prior systemic therapy for BTC, including immunotherapy, targeted therapy, or chemotherapy;
  • History of other prior or concurrent malignancies, except those with complete treatment and disease-free survival for more than 5 years;
  • Presence of an active, known or suspected autoimmune disease, or requirement for long-term systemic corticosteroid therapy (equivalent to ≥ 10 mg prednisone daily) or other immunosuppressive agents. Participants using inhaled or topical corticosteroids will not be excluded;
  • Presence of ascites, hepatic encephalopathy, sclerosing cholangitis, or other concurrent organ dysfunctions that would preclude tolerance of general anesthesia or hepatectomy;
  • Women who are breastfeeding or pregnant;
  • Any other factors that, in the investigator's judgment, may compromise participant safety or trial compliance, including serious comorbidities requiring ongoing treatment, clinically significant laboratory abnormalities, or relevant social or family-related issues.

Trial locations and contacts

No sites are listed yet. Contact the study team or a site near you to ask about taking part.

Yifan Tong, Ph.D contact

86 571 86006271

tongyf@zju.edu.cn

About this study

Official title: The Efficacy and Safety of Gemcitabine-Cisplatin Plus Envafolimab as Neoadjuvant Therapy in Resectable Biliary Tract Malignancies at High Risk of Recurrence

This trial is to evaluate the efficacy of Gemcitabine-Cisplatin (GC) plus Envafolimab neoadjuvant therapy in the patients at high risk of recurrence. Primary endpoint: Major Pathologic Response (MPR). It will also learn about the safety of drug including Gemcitabine-Cisplatin (GC) plus Envafolimab as a neoadjuvant therapy in this trial.

Read the detailed description

This trial is a single-arm interventional clinical study to evaluate the efficacy and safety of neoadjuvant gemcitabine-cisplatin plus Envafolimab in resectable biliary tract malignancies patients with high-risk of recurrence. Patients with high-risk factors for recurrence. The criteria were defined as meeting at least one of the following: a. Preoperative CA19-9 ≥ 200 U/mL; b. Tumor diameter ≥5 cm or multiple tumor nodules on imaging; c. Regional lymph node metastasis with a short-axis diameter ≥ 1.0 cm on imaging; d. Vascular invasion (portal vein or hepatic artery) on imaging; e. Low or undifferentiated histologic grade. The primary endpoint: Major Pathologic Response (MPR). Secondary endpoints: Overall Survival (OS), Disease-free survival (DFS), Objective Response Rate (ORR) per the Response Evaluation Criteria In Solid Tumors (RECIST v1.1), Pathologic Response Rate (PCR), and R0 resection rate. The incidence and severity of adverse events (AEs), serious adverse events (SAEs), and laboratory test abnormalities judged as per the CTCAE v5.0 criteria. Exploratory endpoint: Relationship between carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), Pathological biomarker expression, spatial transcriptome (if samples are sufficient), gut microbiome metagenome sequencing, and treatment response.

Being tested
Neoadjuvant therapy followed by surgery
Keywords
Resectable Biliary Tract Cancer, High Risk of Recurrence
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.

  • Neoadjuvant therapy followed by surgeryDrug

    Also called Envafolimab, Gemcitabine, Cisplatin; Neoadjuvant GC-Envafolimab for Resectable Biliary Tract Malignancies

    First:

    Envafolimab: 400 mg on Day 1, repeated every 3 weeks (Q3W). GC chemotherapy: Gemcitabine: 1000 mg/m2 in 100 mL of 0.9% sodium chloride injection, administered intravenously over 30 minutes on Days 1 and 8, repeated Q3W. Cisplatin: 25 mg/m2 in 500 mL of 5% glucose injection, administered intravenously over 2 hours on Day 1 and 8, repeated Q3W.

    Of note, no target drugs is involved.

    Second:

    Radical resection eligibility will be assessed by the investigator; those with indeterminate resectability require additional MDT discussion confirmation. The criteria for radical resection:

    1. No invasion of the main trunk of the hepatic vein, portal vein, or inferior vena cava;
    2. No distant metastasis except for hilar lymph node metastases;
    3. Minimum distance between surgical margin and tumor border ≥ 0.5 cm;
    4. Residual liver volume ≥ 30% (≥ 40% for participants with cirrhosis).
Study groups in NCT07599995
Study groupRoleWhat they receive
GC Chemotherapy Plus Envafolimab ArmExperimentalParticipants first receive GC chemotherapy plus envafolimab every 3 weeks (Q3W) for a total of 3 cycles (each cycle is 21 days). Eligibility for surgery is then assessed; eligible patients undergo radical resection.
Receives: Drug: Neoadjuvant therapy followed by surgery

What is being measured

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

  1. Major Pathologic Response (MPR)

    MPR is defined as ≤10% residual viable tumor cells in the primary lesion and regional lymph nodes following neoadjuvant therapy, with Pathologic Response Rate (PCR, 0% viable tumor cells) included in the MPR definition.

    Measured: From enrollment to 2-4 weeks after completion of thrid cycle (each cycle is 21 days) of neoadjuvant therapy, surgical pathological findings will be obtained, or patients will be assessed as unresectable.

Secondary outcomes (6)

  1. Residual viable tumor cell ratio

    Postoperative resected specimens are analyzed via pathological section to determine the residual viable tumor cell ratio

    Measured: From enrollment to 2-4 weeks after completion of thrid cycle (each cycle is 21 days) of neoadjuvant therapy, surgical pathological findings will be obtained, or patients will be assessed as unresectable.

  2. Objective Response Rate (ORR)

    ORR is defined as the sum of Complete Response (CR) and Partial Response (PR), representing the proportion of participants with sustained tumor regression meeting predefined criteria.

    Measured: From enrollment until 2-4 weeks after completion of neoadjuvant therapy (three cycles, each cycle is 21 days)

  3. Pathologic Response Rate (PCR)

    No viable tumor cells are found in the review of pathological sections.

    Measured: From enrollment to 2-4 weeks after completion of thrid cycle (each cycle is 21 days) of neoadjuvant therapy, surgical pathological findings will be obtained, or patients will be assessed as unresectable.

  4. R0 resection

    R0 resection rate refers to the proportion of patients achieving complete surgical resection with negative margins.

    Measured: From enrollment to 2-4 weeks after completion of thrid cycles (each cycle is 21 days) of neoadjuvant therapy, surgical pathological findings will be obtained, or patients will be assessed as unresectable.

  5. Overall Survival (OS)

    OS is defined as the time from participant receiving the first treatment until death from any cause.

    Measured: From enrollment up to 2 years following treatment initiation

  6. Disease-free survival (DFS)

    DFS is defined as the time from the date of surgery to neoplasm recurrence or death for participants without residual lesions after surgery, whichever occurs first.

    Measured: From enrollment up to 2 years following treatment initiation

Timeline

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

  1. First posted20 May 2026
  2. Study start30 May 2026 (estimated)
  3. Primary completion30 Mar 2028 (estimated)
  4. Study completion30 Mar 2030 (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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
The detailed schedule for each cycle is as follows: 1) Envafolimab: 400 mg on Day 1, repeated every 3 weeks (Q3W). 2) GC chemotherapy: Gemcitabine: 1000 mg/m2 in 100 mL of 0.9% sodium chloride injection, administered intravenously over 30 minutes on Days 1 and 8, repeated Q3W. Cisplatin: 25 mg/m2 in 500 mL of 5% glucose injection, administered intravenously over 2 hours on Day 1 and 8, repeated Q3W.
Masking
None (open label)
Enrolment
34 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07599995
Sponsor's protocol ID
SRRSH
Acronym
GENE
Status last verified
May 2026
First submitted
28 Apr 2026
Last updated
20 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: After study completion and publication of study results, other individuals or groups may apply to the study executive committee for data sharing.

Publications

  • Valle JW, Kelley RK, Nervi B, Oh DY, Zhu AX. Biliary tract cancer. Lancet. 2021 Jan 30;397(10272):428-444. doi: 10.1016/S0140-6736(21)00153-7.

    PubMed 33516341

  • Zhao Z, Wu H, Han J, Jiang K. Global trends and disparities in gallbladder and biliary tract cancers: insights from the global burden of disease study 2021. Eur J Gastroenterol Hepatol. 2025 May 1;37(5):573-584. doi: 10.1097/MEG.0000000000002947. Epub 2025 Feb 14.

    PubMed 39975993

  • Wang Y, Xun Z, Yang X, Wang Y, Wang S, Xue J, Zhang N, Yang X, Lu Z, Zhou J, Zhou K, Sang X, Zhao H. Local-regional therapy combined with toripalimab and lenvatinib in patients with advanced biliary tract cancer. Am J Cancer Res. 2023 Mar 15;13(3):1026-1037. eCollection 2023.

    PubMed 37034211

  • von Minckwitz G, Huang CS, Mano MS, Loibl S, Mamounas EP, Untch M, Wolmark N, Rastogi P, Schneeweiss A, Redondo A, Fischer HH, Jacot W, Conlin AK, Arce-Salinas C, Wapnir IL, Jackisch C, DiGiovanna MP, Fasching PA, Crown JP, Wulfing P, Shao Z, Rota Caremoli E, Wu H, Lam LH, Tesarowski D, Smitt M, Douthwaite H, Singel SM, Geyer CE Jr; KATHERINE Investigators. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med. 2019 Feb 14;380(7):617-628. doi: 10.1056/NEJMoa1814017. Epub 2018 Dec 5.

    PubMed 30516102

  • Le Roy B, Gelli M, Pittau G, Allard MA, Pereira B, Serji B, Vibert E, Castaing D, Adam R, Cherqui D, Sa Cunha A. Neoadjuvant chemotherapy for initially unresectable intrahepatic cholangiocarcinoma. Br J Surg. 2018 Jun;105(7):839-847. doi: 10.1002/bjs.10641. Epub 2017 Aug 31.

    PubMed 28858392

  • Oh DY, Ruth He A, Qin S, Chen LT, Okusaka T, Vogel A, Kim JW, Suksombooncharoen T, Ah Lee M, Kitano M, Burris H, Bouattour M, Tanasanvimon S, McNamara MG, Zaucha R, Avallone A, Tan B, Cundom J, Lee CK, Takahashi H, Ikeda M, Chen JS, Wang J, Makowsky M, Rokutanda N, He P, Kurland JF, Cohen G, Valle JW. Durvalumab plus Gemcitabine and Cisplatin in Advanced Biliary Tract Cancer. NEJM Evid. 2022 Aug;1(8):EVIDoa2200015. doi: 10.1056/EVIDoa2200015. Epub 2022 Jun 1.

    PubMed 38319896

  • Pereira RA, Barcellos G, Lenz G, Pereira AAL, Biachi de Castria T. Neoadjuvant Chemotherapy in Resectable Biliary Tract Cancer: A Systematic Review and Metanalysis. J Surg Oncol. 2026 Mar;133(3):313-325. doi: 10.1002/jso.70169. Epub 2025 Dec 22.

    PubMed 41424434

  • Chen F, Sheng J, Li X, Gao Z, Hu L, Chen M, Fei J, Song Z. Tumor-associated macrophages: orchestrators of cholangiocarcinoma progression. Front Immunol. 2024 Sep 3;15:1451474. doi: 10.3389/fimmu.2024.1451474. eCollection 2024.

    PubMed 39290697

  • Chen C, Chen Z, Chen D, Zhang B, Wang Z, Le H. Suppressive effects of gemcitabine plus cisplatin chemotherapy on regulatory T cells in nonsmall-cell lung cancer. J Int Med Res. 2015 Apr;43(2):180-7. doi: 10.1177/0300060514561504. Epub 2015 Feb 6.

    PubMed 25659373

  • Xue Y, Gao S, Gou J, Yin T, He H, Wang Y, Zhang Y, Tang X, Wu R. Platinum-based chemotherapy in combination with PD-1/PD-L1 inhibitors: preclinical and clinical studies and mechanism of action. Expert Opin Drug Deliv. 2021 Feb;18(2):187-203. doi: 10.1080/17425247.2021.1825376. Epub 2020 Oct 5.

    PubMed 32954856

  • Chen Y, Zhang J, Hu W, Li X, Sun K, Shen Y, Zhang M, Wu J, Gao S, Yu J, Que R, Zhang Y, Yang F, Xia W, Zhang A, Tang X, Bai X, Liang T. Envafolimab plus lenvatinib and transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma: a prospective, single-arm, phase II study. Signal Transduct Target Ther. 2024 Oct 9;9(1):280. doi: 10.1038/s41392-024-01991-1.

    PubMed 39384742

  • Shi GM, Huang XY, Liang F, Liang X, Dong R, Ye QH, Gao Q, Ji Y, Yu ZP, Zhai WL, Lu JC, Li XW, Liu FB, Wang K, Yang W, Zhang JL, Hu ZQ, Qiu SJ, Wang XY, Yang XR, Sun HC, Shi YH, Ding ZB, Liu WR, Huang XW, Huang C, Shen YH, Sun J, He YF, Peng YF, Xu Y, Zou JJ, Zhou J, Fan J; ZSAB Study Group. Neoadjuvant GOLP in Resectable High-Risk Intrahepatic Cholangiocarcinoma. N Engl J Med. 2026 Mar 5;394(10):983-995. doi: 10.1056/NEJMoa2513918.

    PubMed 41780001

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Neoadjuvant therapy followed by surgery in people with Biliary Tract Cancer, run by Sir Run Run Shaw Hospital.

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 8 inclusion and 7 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 20 May 2026. Status can change between updates, so confirm with the study contact before making plans.

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 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.

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 Yifan Tong, Ph.D (86 571 86006271, tongyf@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Major Pathologic Response (MPR) (time frame: From enrollment to 2-4 weeks after completion of thrid cycle (each cycle is 21 days) of neoadjuvant therapy, surgical pathological findings will be obtained, or patients will be assessed as unresectable.). 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 NCT07599995, 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 20 May 2026; AzTrials last refreshed its copy on 6 Nov 2026.

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