Bile Duct CarcinomaPhase 2SAIBNCT07025174
Sequential Anti-Angiogenic Therapy After Immunotherapy in Advanced Biliary Tract Cancer
A Phase 2 study testing PD-1/CTLA-4 Dual Functional Antibody, Gemcitabine, Cisplatin and Anlotinib in people with Bile Duct Carcinoma and Gall Bladder Cancer, run by First Affiliated Hospital of Zhejiang University at 1 site in China.
Trial summary
Brief Summary: This study is for patients with advanced biliary tract cancer (cancer of the bile ducts or gallbladder). The purpose is to find out if using anti-blood vessel formation drugs after immunotherapy treatment can help patients live longer without their cancer getting worse. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Bile Duct Carcinoma, Gall Bladder Cancer, Biliary Tract Cancer
- What is being tested?
- PD-1/CTLA-4 Dual Functional Antibody, Gemcitabine, Cisplatin and Anlotinib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteChina
- Study dates
- 1 Jun 2025to 31 Dec 2027
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-75 years at time of enrollment; Histologically or cytologically confirmed advanced or metastatic biliary tract adenocarcinoma (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder carcinoma); Unresectable locally advanced or metastatic disease not amenable to curative treatment; At least one measurable lesion according to RECIST version 1.1 criteria; ECOG Performance Status 0-1; Life expectancy ≥ 12 weeks; No prior systemic chemotherapy, immunotherapy, or anti-angiogenic therapy for advanced disease (adjuvant therapy completed >6 months prior is allowed); Adequate bone marrow function: ANC ≥1.5×10⁹/L, platelets ≥100×10⁹/L, hemoglobin ≥90 g/L; Adequate liver function: Total bilirubin ≤2.5×ULN, ALT and AST ≤3×ULN (or ≤5×ULN if liver metastases present); Adequate renal function: Serum creatinine ≤1.5×ULN or creatinine clearance ≥50 mL/min; Signed informed consent.
Who cannot join
- Mixed histology tumors or neuroendocrine components; Active central nervous system metastases (treated and stable metastases >4 weeks allowed); History of other malignancies within 5 years (except adequately treated basal cell carcinoma, squamous cell carcinoma of skin, or carcinoma in situ); Active autoimmune disease requiring systemic treatment; History of severe allergic reactions to monoclonal antibodies or study drug components; Uncontrolled hypertension (>140/90 mmHg despite medication); Significant cardiovascular disease including unstable angina, myocardial infarction within 6 months, or NYHA Class III-IV heart failure; Active bleeding or bleeding tendency, thrombosis, or use of anticoagulants; Major surgery within 4 weeks or minor surgery within 2 weeks; Active infection requiring systemic treatment; Pregnancy or breastfeeding; HIV infection, active hepatitis B or C infection; Psychiatric illness that would limit compliance with study requirements.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
The First Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310003
Zhen Liu, MD, 86-571-87235407, liuzhen@cancer.ac.cn
Jianzhen Shan, MD
About this study
Official title: Evaluation of the Effect of Sequential Anti-angiogenic Therapy Following Immune Therapy Progression on Survival in Patients With Advanced Biliary Tract Malignancies: A Randomized, Multi-center, Exploratory Clinical Study
Brief Summary:
This study is for patients with advanced biliary tract cancer (cancer of the bile ducts or gallbladder). The purpose is to find out if using anti-blood vessel formation drugs after immunotherapy treatment can help patients live longer without their cancer getting worse.
Read more
What the study compares:
Control group: Patients receive standard chemotherapy as first-line treatment, then chemotherapy plus anlotinib (an anti-blood vessel drug) if their cancer progresses Treatment group: Patients receive chemotherapy plus immunotherapy as first-line treatment, then the same second-line treatment as the control group if their cancer progresses
Who can join:
Patients aged 18-75 with advanced biliary tract cancer that has been confirmed by tissue testing, who have not received immunotherapy or anti-blood vessel drugs before, and who are in good enough health for treatment.
What we want to learn:
The main goal is to see if patients who received immunotherapy first have better outcomes when they later receive anti-blood vessel treatment. We will measure how long patients live without their cancer getting worse during second-line treatment.
Study design:
This is a randomized study, meaning patients are assigned by chance to one of the two treatment groups. About 60 patients will participate across multiple hospitals in China. We will also collect blood and tissue samples to better understand how these treatments work.
The study will help doctors determine if this treatment sequence could become a new standard approach for patients with advanced biliary tract cancer.
- Being tested
- PD-1/CTLA-4 Dual Functional Antibody, Gemcitabine, Cisplatin, Anlotinib, Oxaliplatin + 5-Fluorouracil/Leucovorin
- Keywords
- Biliary tract cancer, Immunotherapy, Anti-angiogenic therapy, Anlotinib, Sequential therapy
- Medical subject headings
- Bile Duct Neoplasms, Gallbladder Neoplasms, Biliary Tract Neoplasms, Cholangiocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PD-1/CTLA-4 Dual Functional AntibodyDrug
PD-1/CTLA-4 Dual Functional Antibody (iparomlimab and tuvonralimab injection):
5 mg/kg intravenous infusion every 3 weeks (day 1 of each 21-day cycle) for up to 6 cycles, with potential for maintenance therapy continuation. Used in combination with GP regimen in experimental arm only. This is a novel dual-functional antibody targeting both PD-1 and CTLA-4 pathways simultaneously.
Gemcitabine, CisplatinDrug
Gemcitabine 1000 mg/m² d1,8+Cisplatin 25mg/m² d1,8
AnlotinibDrug
10mg po d1-14 q3w
Oxaliplatin + 5-Fluorouracil/LeucovorinDrug
XELOX (oxaliplatin 130mg/m² d1+capecitabine 1000mg/m² d1-14 q3w) or FOLFOX6 (Oxaliplatin 85 mg/m², leucovorin 400 mg/m², fluorouracil 400 mg/m² intravenous bolus followed by fluorouracil 2400 mg/m² 46 hours, q2w)
| Study group | Role | What they receive |
|---|---|---|
| Standard Chemotherapy First-line | Active comparator | Patients receive standard gemcitabine plus cisplatin (GP) chemotherapy as first-line treatment for up to 6 cycles. Upon disease progression, patients receive second-line treatment with XELOX or FOLFOX chemotherapy plus anlotinib. Receives: Drug: Gemcitabine, Cisplatin; Drug: Anlotinib; Drug: Oxaliplatin + 5-Fluorouracil/Leucovorin |
| Immunotherapy Plus Chemotherapy First-line | Experimental | Patients receive gemcitabine plus cisplatin (GP) chemotherapy combined with PD-1/CTLA-4 dual functional antibody as first-line treatment for up to 6 cycles. Upon disease progression, patients receive the same second-line treatment as the control group with XELOX or FOLFOX chemotherapy plus anlotinib. Receives: Drug: PD-1/CTLA-4 Dual Functional Antibody; Drug: Gemcitabine, Cisplatin; Drug: Anlotinib; Drug: Oxaliplatin + 5-Fluorouracil/Leucovorin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free Survival (PFS) of Second-Line Treatment
Progression-free survival defined as the time from initiation of second-line chemotherapy plus anlotinib treatment until radiographic disease progression per RECIST 1.1 criteria or death from any cause, whichever occurs first. Disease progression will be assessed by CT or MRI imaging every 2 treatment cycles (approximately every 6 weeks). This outcome measure specifically evaluates whether patients who received first-line immunotherapy plus chemotherapy have improved PFS during second-line anti-angiogenic treatment compared to patients who received first-line chemotherapy alone.
Measured: From the start of second-line treatment until disease progression or death from any cause, assessed up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2025
- Study start1 Jun 2025
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bile Duct CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- First Affiliated Hospital of Zhejiang University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tingbo Liang, MD, Principal investigator, Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07025174
- Sponsor's protocol ID
- IIT20250065C-R1
- Acronym
- SAIB
- Status last verified
- May 2025
- First submitted
- 10 Jun 2025
- Last updated
- 17 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Effect of Sequential Anti-angiogenic Therapy Following Immune Therapy Progression on Survival in Patients With Advanced Biliary Tract Malignancies: A Randomized, Multi-center, Exploratory Clinical Study
- ClinicalTrials.gov ID
- NCT07025174
- Acronym / sponsor ID
- SAIB / IIT20250065C-R1
- Keywords
- Biliary tract cancer, Immunotherapy, Anti-angiogenic therapy, Anlotinib, Sequential therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- First Affiliated Hospital of Zhejiang UniversityUniversity, hospital or other
- Study start
- 1 Jun 2025 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 17 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Brief Summary:
This study is for patients with advanced biliary tract cancer (cancer of the bile ducts or gallbladder). The purpose is to find out if using anti-blood vessel formation drugs after immunotherapy treatment can help patients live longer without their cancer getting worse.
What the study compares:
Control group: Patients receive standard chemotherapy as first-line treatment, then chemotherapy plus anlotinib (an anti-blood vessel drug) if their cancer progresses Treatment group: Patients receive chemotherapy plus immunotherapy as first-line treatment, then the same second-line treatment as the control group if their cancer progresses
Who can join:
Patients aged 18-75 with advanced biliary tract cancer that has been confirmed by tissue testing, who have not received immunotherapy or anti-blood vessel drugs before, and who are in good enough health for treatment.
What we want to learn:
The main goal is to see if patients who received immunotherapy first have better outcomes when they later receive anti-blood vessel treatment. We will measure how long patients live without their cancer getting worse during second-line treatment.
Study design:
This is a randomized study, meaning patients are assigned by chance to one of the two treatment groups. About 60 patients will participate across multiple hospitals in China. We will also collect blood and tissue samples to better understand how these treatments work.
The study will help doctors determine if this treatment sequence could become a new standard approach for patients with advanced biliary tract cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard Chemotherapy First-line | Active comparator | Drug: Gemcitabine, Cisplatin, Drug: Anlotinib, Drug: Oxaliplatin + 5-Fluorouracil/LeucovorinPatients receive standard gemcitabine plus cisplatin (GP) chemotherapy as first-line treatment for up to 6 cycles. Upon disease progression, patients receive second-line treatment with XELOX or FOLFOX chemotherapy plus anlotinib. |
| Immunotherapy Plus Chemotherapy First-line | Experimental | Drug: PD-1/CTLA-4 Dual Functional Antibody, Drug: Gemcitabine, Cisplatin, Drug: Anlotinib, Drug: Oxaliplatin + 5-Fluorouracil/LeucovorinPatients receive gemcitabine plus cisplatin (GP) chemotherapy combined with PD-1/CTLA-4 dual functional antibody as first-line treatment for up to 6 cycles. Upon disease progression, patients receive the same second-line treatment as the control group with XELOX or FOLFOX chemotherapy plus anlotinib. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Age 18-75 years at time of enrollment; Histologically or cytologically confirmed advanced or metastatic biliary tract adenocarcinoma (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder carcinoma); Unresectable locally advanced or metastatic disease not amenable to curative treatment; At least one measurable lesion according to RECIST version 1.1 criteria; ECOG Performance Status 0-1; Life expectancy ≥ 12 weeks; No prior systemic chemotherapy, immunotherapy, or anti-angiogenic therapy for advanced disease (adjuvant therapy completed >6 months prior is allowed); Adequate bone marrow function: ANC ≥1.5×10⁹/L, platelets ≥100×10⁹/L, hemoglobin ≥90 g/L; Adequate liver function: Total bilirubin ≤2.5×ULN, ALT and AST ≤3×ULN (or ≤5×ULN if liver metastases present); Adequate renal function: Serum creatinine ≤1.5×ULN or creatinine clearance ≥50 mL/min; Signed informed consent.
Key exclusion criteria (1 listed)
- Mixed histology tumors or neuroendocrine components; Active central nervous system metastases (treated and stable metastases >4 weeks allowed); History of other malignancies within 5 years (except adequately treated basal cell carcinoma, squamous cell carcinoma of skin, or carcinoma in situ); Active autoimmune disease requiring systemic treatment; History of severe allergic reactions to monoclonal antibodies or study drug components; Uncontrolled hypertension (>140/90 mmHg despite medication); Significant cardiovascular disease including unstable angina, myocardial infarction within 6 months, or NYHA Class III-IV heart failure; Active bleeding or bleeding tendency, thrombosis, or use of anticoagulants; Major surgery within 4 weeks or minor surgery within 2 weeks; Active infection requiring systemic treatment; Pregnancy or breastfeeding; HIV infection, active hepatitis B or C infection; Psychiatric illness that would limit compliance with study requirements.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PD-1/CTLA-4 Dual Functional AntibodyPD-1/CTLA-4 Dual Functional Antibody (iparomlimab and tuvonralimab injection): 5 mg/kg intravenous infusion every 3 weeks (day 1 of each 21-day cycle) for up to 6 cycles, with potential for maintenance therapy continuation. Used in combination with GP regimen in experimental arm only. This is a novel dual-functional antibody targeting both PD-1 and CTLA-4 pathways simultaneously. | Drug | Immunotherapy Plus Chemotherapy First-line |
| Gemcitabine, CisplatinGemcitabine 1000 mg/m² d1,8+Cisplatin 25mg/m² d1,8 | Drug | Immunotherapy Plus Chemotherapy First-line, Standard Chemotherapy First-line |
| Anlotinib10mg po d1-14 q3w | Drug | Immunotherapy Plus Chemotherapy First-line, Standard Chemotherapy First-line |
| Oxaliplatin + 5-Fluorouracil/LeucovorinXELOX (oxaliplatin 130mg/m² d1+capecitabine 1000mg/m² d1-14 q3w) or FOLFOX6 (Oxaliplatin 85 mg/m², leucovorin 400 mg/m², fluorouracil 400 mg/m² intravenous bolus followed by fluorouracil 2400 mg/m² 46 hours, q2w) | Drug | Immunotherapy Plus Chemotherapy First-line, Standard Chemotherapy First-line |
Primary outcome
Progression-Free Survival (PFS) of Second-Line Treatment
Time frame: From the start of second-line treatment until disease progression or death from any cause, assessed up to 24 months
Progression-free survival defined as the time from initiation of second-line chemotherapy plus anlotinib treatment until radiographic disease progression per RECIST 1.1 criteria or death from any cause, whichever occurs first. Disease progression will be assessed by CT or MRI imaging every 2 treatment cycles (approximately every 6 weeks). This outcome measure specifically evaluates whether patients who received first-line immunotherapy plus chemotherapy have improved PFS during second-line anti-angiogenic treatment compared to patients who received first-line chemotherapy alone.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Tingbo Liang, MD principal investigator
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PD-1/CTLA-4 Dual Functional Antibody, Gemcitabine, Cisplatin and Anlotinib in people with Bile Duct Carcinoma and Gall Bladder Cancer, run by First Affiliated Hospital of Zhejiang 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 1 inclusion and 1 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: looking for participants now, as of the sponsor's last update on 17 Jun 2025. 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 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 Zhen Liu, MD (86-571-87235407, liuzhen@cancer.ac.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-Free Survival (PFS) of Second-Line Treatment (time frame: From the start of second-line treatment until disease progression or death from any cause, assessed up to 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Jun 2025.