Anlotinib in Combination With PD1 With Gemcitabine Plus(+)Cisplatin for Unresectable or Metastatic Biliary Tract Cancer

NCT04300959 | Unknown Phase 2

• 1 other identifier: ALTNZJ-004
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the efficacy and safety of Anlotinib Hydrochloride in Combination With PD1 With Gemcitabine Plus(+)Cisplatin Compared With Gemcitabine +Cisplatin as First-line Chemotherapy for Unresectable or Metastatic Biliary Tract Cancer

Conditions

Biliary Tract Cancer

Outcome Measures

Primary Outcomes (1)

• 12 months OS rate

  The definition of 12-months OS rate is the percentage of patients who had NOT has an event before or at 12 months

  360 days

Secondary Outcomes (4)

• Overall Survival (OS)

  up to 24 months after enrollment or study close

• Progress free survival (PFS)

  up to 24 months after enrollment or study close

• Objective response rate(ORR)

  up to 24 months after enrollment or study close

• Incidence of Treatment-Emergent 3/4 Adverse Events

  up to 24 months after enrollment or study close

Study Arms (2)

Experimental group

EXPERIMENTAL

Anlotinib in combination with Sintilimab with Gemcitabine plus(+)Cisplatin

Drug: Anlotinib Hydrochloride in Combination With PD1 With Gemcitabine Plus(+)Cisplatin

Control group

ACTIVE COMPARATOR

Standard platinum-based chemotherapy

Drug: Gemcitabine Plus(+)Cisplatin

Interventions

Anlotinib Hydrochloride in Combination With PD1 With Gemcitabine Plus(+)Cisplatin DRUG

Gemcitabine:1000mg/m2, days 1 and 8; Cisplatin: 25mg/m2, days 1 and 8； Anlotinib : 10mg po qd, days 1-14; Sintilimab: 200mg IV, day 1； 1 cycle = 3 weeks.

Also known as: AL3818, IBI308

Experimental group

Gemcitabine Plus(+)Cisplatin DRUG

Gemcitabine:1g/m2, days 1 and 8; Cisplatin: 25mg/m2, days 1 and 8； 1 cycle = 3 weeks.

Control group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who are voluntary and sign an informed consent document.
• Age between 18-70 years (including 18 and 70), no gender preference.
• Expected survival ≥ 12 weeks
• ECOG performance status 0 or 1 within 7 days prior to the first dose.
• In women of child-bearing age, pregnancy test should be negative within 28 days prior to registration, and effective contraception during the treatment period should be adopted within 60 days after the last dose. In this trial, women of child-bearing age are defined as sexually mature women with: 1) no history of hysterectomy or bilateral ovariectomy; 2) natural menopause \< continuous 24 months (amenorrhea after cancer treatment does not preclude fertility) (i.e., having menstruation at any time within preceding continuous 24 months); female spouses of male subjects who are of child-bearing age should also follow the above contraceptive requirements.
• Adequate organ function.
• Blood test (no blood transfusion, no usage of G-CSF and no medication for correction within 14 days prior to screening):
• neutrophil count ≥ 1.5×109/L
• platelets ≥ 75×109/L
• hemoglobin ≥ 90g/L
• Biochemical test (no albumin transfusion within 14 days prior to screening):
• serum creatinine ≤ 1.5× upper limit normal (ULN), or creatinine clearance \> 50 mL/min;
• total bilirubin ≤ 1.5×ULN (total bilirubin ≤ 3× ULN in patients with Gilbert syndrome);
• AST and ALT ≤ 2.5× ULN; for patients with hepatic metastases, AST and ALT ≤ 5× ULN;
• INR ≤ 2.3 or prothrombin time (PT) exceeding normal control range ≤ 6 seconds;

You may not qualify if:

• Patients who meet any of the following conditions will be excluded from the trial:
• Patients who previously received systemic treatment for advanced unresectable or metastatic cholangiocarcinoma will be excluded. Neoadjuvant or adjuvant therapy is acceptable if treatment is completed at least 6 months prior to randomization and shows no progression.
• Patients suffering from other active malignancies within 5 years or coexisting with cholangiocarcinoma, except adequately treated localized neoplasms including, but not limited to: basal cell or squamous cell skin cancer, superficial bladder cancer, in situ prostate cancer, in situ cervical cancer, and in situ breast cancer.
• Patients who are preparing for or have previously undergone organ or allogenic bone marrow transplantation.
• Patients with symptomatic moderate or severe ascites requiring paracentesis and drainage (except patients with imaging showing mild ascites but no clinical symptoms); or patients with uncontrolled or moderate and severe pleural or pericardial effusion.
• Patients who have a history of gastrointestinal hemorrhage within preceding 6 months or gastrointestinal hemorrhagic tendency, e.g., esophagogastric varices with a risk of hemorrhage, active peptic ulcer, fecal occult blood being continuously positive (if fecal occult blood is positive at baseline, reexamination can be considered; if reexamination is still positive, esophagogastroduodenoscopy (EGD) should be considered; if EGD indicates esophagogastric varices with a risk of hemorrhage, then the patient will be excluded).
• Patients with hereditary or acquired bleeding tendency (e.g., coagulation dysfunction) or thrombophilia, e.g., hemophilia patients; or patients who are currently receiving or recently received (within preceding 10 days) full-dose anticoagulant or thrombolytic agents orally or by injection for therapeutic purposes (prophylactic usage of low-dose aspirin or low molecular heparin is acceptable).
• Patients who are receiving or recently received (within preceding 10days) aspirin (\>325 mg/d (maximum antiplatelet dose)) or dipyridamole, ticlopidine, clopidogrel and cilostazol.
• Patients who have a history of thrombosis or embolism within preceding 6 months, including cerebrovascular events (transient ischemic attack, cerebral hemorrhage and cerebral infraction) and pulmonary embolism.
• Patients with uncontrolled heart disease or relevant symptoms, e.g., (1) heart failure with NYHA \> 2 (Appendix 5) or UCG showing LVEF \<50%; (2) unstable angina; (3) a history of myocardial infraction within preceding 1 year; (4) supraventricular or ventricular arrhythmia with clinical significance indicating treatment or intervention; (5) QTc \> 450ms (male); QTc \> 470ms(female) (QTc is calculated by Fridericia law; if QTc is abnormal, it can be continuously measured 3 times with an interval of 2 minutes, taking the average).
• Patients with hypertension uncontrolled by drug or treatment (SBP≥140 mmHg or DBP≥90 mmHg) (based on≥2 measurements and taking average); or patients with a history of hypertensive emergency or hypertensive encephalopathy.
• Patients who have severe vascular diseases (e.g., aortic aneurysm requiring surgical repair or with recent peripheral arterial thrombosis) within preceding 6 months.
• Patients with severe, unhealed or open wounds, and active ulcers or untreated fractures.
• Patients who received major operation (except diagnosis) within preceding 4 weeks, or who are expected to receive major operation during the trial period.
• Patients who are unable to swallow tablets, or with malabsorption syndrome or any condition that may affect gastrointestinal absorption.

Sponsors & Collaborators

• Zhejiang Cancer Hospital: lead

Study Sites (1)

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

RECRUITING

Related Publications (1)

• Li J, Zhou S, Xu X, Zheng Q, Zhang F, Luo C, Li D, Sun X, Han Z, Wu W, Yan J, Shao Y, Zhang Y, Wu B, Wei Q, Wang X, Zhou Y, Sun W, Xu Q, Ying J. Sintilimab and anlotinib with gemcitabine plus cisplatin in advanced biliary tract cancer: SAGC a randomized phase 2 trial. Nat Commun. 2025 Jul 1;16(1):5559. doi: 10.1038/s41467-025-60119-3.

  PMID: 40593475 DERIVED

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

anlotinib; sintilimab

Condition Hierarchy (Ancestors)

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

Study Officials

• Jieer Ying

  Zhejiang Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jingjing Li

CONTACT

18258255285; 348519870@qq.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2020
• First Posted: March 9, 2020
• Study Start: January 1, 2020
• Primary Completion: January 1, 2021
• Study Completion: January 1, 2022
• Last Updated: March 9, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)