Biliary Tract CancerPhase 2NCT03796429
A Study of the Efficacy and Safety of Chemotherapy Combined With Toripalimab in Advanced Biliary Tract Cancer
A Phase 2 study testing GS+Toripalimab in people with Biliary Tract Cancer, run by Shanghai Zhongshan Hospital at 1 site in China.
Trial summary
1. Target population: patients with advanced biliary tract cancer (including gallbladder carcinoma, intrahepatic and extrahepatic cholangiocarcinoma) . 2. Primary objective: progression free survival (PFS)/ overall survival (OS) of first-line chemotherapy plus PD-1 antibody (Toripalimab) in patients with advanced… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Biliary Tract Cancer
- What is being tested?
- GS+Toripalimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteChina
- Study dates
- 17 Dec 2018to 30 Mar 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Male or female. Age ≥ 18 years and ≤75 years.
- histologically documented advanced biliary duct cancer, including gallbladder cancer, intrahepatic and extrahepatic cholangiocarcinoma, specimen within a year available for test (at least 10 pathological sections) .
- at least one measurable lesion in abdominal CT/MRI according to RESIST 1.1 is required.
- Karnofsky score≥ 80.
- Adequate hematological function: Neutrophil count ≥ 1.5 × 109/L, Platelets ≥ 100 × 109/L and Hemoglobin ≥90g/L.
- Adequate liver function: Total bilirubin ≤ 1.5 × upper limit of normal (ULN); AST (SGOT) and ALT (SGPT) < 2.5 × ULN in the absence of liver metastases, or < 5 × ULN in case of liver metastases. ALP ≤ 2.5 × upper limit of normal (ULN); ALB ≥30g/L.
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- Adequate renal function: Serum creatinine ≤ 1.5 x ULN, and creatinine clearance ≥ 60 ml/min.
- Adequate coagulation function: INR/PT≤ 1.5 x ULN, aPTT≤ 1.5 x ULN.
- No serious concomitant disease that will threaten the survival of patients to less than 5 years.
- Written (signed) informed consent.
- Good compliance with the study procedures, including lab and auxiliary examination and treatment.
- Female patients should not be pregnant or breast feeding.
- Agree to take contraception measures during treatment and in 120 days after last dose of Toripalimab or in 180 days after last dose of chemo.
Who cannot join
- history of chemo, radiation, immune therapy or radical resection for the biliary tract cancer, except those patients who relapsed after 6 months since the last time of adjuvant therapy.
- patients with active autoimmune disease or history of refractory autoimmune disease.
- patients with active malignant tumor in recent 2 years, except the tumor studied in this research or cured locally tumor like resected basal cell or squamous cell skin cancer, superficial bladder cancer, cervical or breast carcinoma in situ.
- uncontrollable pleural effusion, pericardial effusion, or ascites in 2 weeks before recruitment.
- patients who have digestive tract bleeding in 2 weeks before recruitment or with high risk of bleeding.
- perforation / fistula of GI tract in 6 months before recruitment.
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- losing over 20% body weight in 2 months before recruitment.
- pulmonary disease history: interstitial pulmonary disease, non-infective pneumonitis, pulmonary fibrosis, acute pulmonary disease.
- uncontrollable systemic diseases, including diabetes, hypertension, etc.
- severe chronic or active infections in need of systemic antibacterial, antifungal, or antiviral treatment, including TB or HIV, etc.
- patients with untreated chronic hepatitis B or HBV DNA over 500 IU/ml or positive HCV RNA.
- patients with any cardiovascular risk factors below:
- cardiac chest pain occurring in 28 days before recruitment, defined as moderate pain that limits daily activity.
- pulmonary embolism with symptoms occurring in 28 days before recruitment.
- acute myocardial infarction occurring in 6 months before recruitment.
- any history of heart failure reaching grade 3/4 of NYHA in 6 months before recruitment.
- ventricular arrhythmias of Grade 2 or grater in 6 months before recruitment, or accompanied by supraventricular tachyarrhythmias requiring medical treatment.
- cerebrovascular accident within 6 months before recruitment.
- patients with peripheral neuropathy NCI CTC AE grade 1, except those with only deep tendon reflex disappearing.
- moderate or severe renal injury [creatinine clearance rate≤50 ml/min (according to Cockroft \& Gault equation)], or Scr>ULN.
- allergic to any drug in this study.
- history of allogeneic stem cell transplantation or organ transplantation.
- use of steroids (dosage>10mg/d prednisone) or other systemic immune suppressive therapy in 14 days before recruitment, except patients treated with regimens below: a. steroids for hormone replacement (dosage>10mg/d prednisone); b. steroids for local application with little systemic absorption; c. short -term (≤ 7 days) steroids for preventing allergy or vomiting.
- vaccinated with live vaccine in 4 weeks before recruitment.
- receiving immune (interleukin, interferon, thymin) treatment or treatment of other trials in 28 days before recruitment.
- receiving palliative radiation in 14 days before recruitment.
- history of anti PD-1, PD-L1, PD-L2 or any other specific T cell co-stimulation or checkpoint pathway targeted treatment.
- receiving operation in 28 days before recruitment, only if the operation is a minimally invasive one e.g. PICC.
- for patients with uncontrolled epilepsy, CNS diseases or history of mental disorder, researchers should evaluate whether their diseases will impede their signing of informed consent or compliance of treatment.
- existing of potential situation which will impede drug administration or affect toxicity analysis or alcohol/ drug abuse.
Trial locations and contacts
1 site in 1 country.
China1 site
Zhongshan Hospital Affiliated to Fudan University
Shanghai, Shanghai Municipality, 200032
About this study
Official title: A Single-arm, Single-center, Prospective Clinical Study of the Efficacy and Safety of Chemotherapy Combined With Toripalimab in the Treatment of Advanced Biliary Tract Cancer
- Target population: patients with advanced biliary tract cancer (including gallbladder carcinoma, intrahepatic and extrahepatic cholangiocarcinoma) .
- Primary objective: progression free survival (PFS)/ overall survival (OS) of first-line chemotherapy plus PD-1 antibody (Toripalimab) in patients with advanced biliary tract cancer.
Secondary objectives:
Read more
- objective response rate (ORR) of first-line chemotherapy plus PD-1 antibody (Toripalimab)
- safety of first-line chemotherapy plus PD-1 antibody (Toripalimab)
3.Trial design: This is a monocenter, single arm, phase II study to evaluate the efficacy and safety of first-line chemotherapy plus PD-1 antibody (Toripalimab) in patients with advanced advanced biliary tract cancer.
4.Treatment plan: Patients will be given treatment as below once recruited: PD-1 antibody Toripalimab（240mg, iv, q3w），combined with GS regimen(gemcitabine 1000mg／m2 ，d1,d8 + S1 40-60mg bid*14d，Q21d).
The treatment will be continued until emerging of disease progression or intolerable adverse effects (The upper time limit for treatment is 2 years).
5.Number of subjects: 40 patients. Number of centers: 1 sites ( Fudan University Affiliated Zhongshan Hospital).
Read the detailed description
Backgrounds:
Toripalimab (JS-001) is a PD-1 antibody developed by Shanghai Jun Shi Biomedical technology Co. Ltd. Nowadays, eighteen clinical trials of this drug have been conducted in patients with different types of advanced malignant tumor. Until now, Toripalimab has exhibited favorable safety in recruited patients. Incidence rate of SAE is 14.7%. JS001-Ib-CRP-1.0 is a phase Ib/II basket trial, aiming at evaluating safety and efficacy of JS001 in treating advanced gastric adenocarcinoma, esophageal squamous cell carcinoma, nasopharyngeal carcinoma and head and neck squamous cell carcinoma.The interim analyses results of 161 patients show that the ORR is 22.4%.
Now, the standard chemotherapies regimen for advanced biliary tract cancer include gemcitabine, platinum and fluorouracil; Considering the synergistic effect of chemotherapy and immune therapy, the investigators choose GS regimen (gemcitabine+S1) to combine Toripalimab.
the investigators will shut down the study in advance, if unpredicted SAE or low efficacy occur.
Patients with abnormal autoimmune status, unfavorable body function, factors impeding drug taking, absorption and metabolism will be excluded. Study participants with disease progression or severe/ intolerant toxicity during treatment will withdraw the study.
Hyper-progressive disease is defined as 1) progression 2) more than doubled growth rate 3) tumor volume increase >50% in 2 months after initialing the treatment.
- Conditions
- Biliary Tract Cancer
- Being tested
- GS+Toripalimab
- Keywords
- Advanced Biliary Tract Cancer, PD-1 antibody(Toripalimab), first-line chemotherapy
- 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.
GS+ToripalimabDrug
Patients will be given treatment as below once recruited: PD-1 antibody Toripalimab（240mg, iv, q3w），combined with GS regimen(gemcitabine 1000mg／m2 ，d1,d8 + S1 40-60mg bid*14d，Q21d).
The treatment will be continued until emerging of disease progression or intolerable adverse effects (The upper time limit for treatment is 2 years).
| Study group | Role | What they receive |
|---|---|---|
| GS+Toripalimab | Experimental | Not described Receives: Drug: GS+Toripalimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
progression free survival (PFS) of GS regimen plus PD-1 antibody (Toripalimab)
PFS is defined as time interval from recruitment to tumor progression or censoring. Tumor progression is defined as below: 1) relapse of primary lesion 2) emerging of new lesion 3) distant metastasis 4) death of any reason 5)tumor progression according to RESIST 1.1 on CT/MRI.
Measured: 36 months after the last subject participating in
overall survival (OS) of GS regimen plus PD-1 antibody (Toripalimab)
OS is defined as time interval from recruitment to all-caused death or censoring.
Measured: 36 months after the last subject participating in
Secondary outcomes (2)
objective response rate (ORR) of GS regimen plus PD-1 antibody (Toripalimab)
rate of patients with complete remission (CR) or partial remission (PR) based on RESIST1.1. ORR was evaluated by chest, abdominal \& pelvic CT/MRI. Evaluation will be conducted every 6 weeks during treatment, and every 0.5 year after all treatments.
Measured: 36 months after the last subject participating in
Incidence of adverse Events of GS regimen plus PD-1 antibody (Toripalimab)
Adverse events (AE) of chemotherapy will be graded and documented according to NCI-CTC AE v4.03 from the beginning of treatment to 1 months after the last date of treatment. Documentary will include severity, lasting period and occurrence time. Main AEs include vomiting, diarrhea, anemia, leukopenia, thrombocytopenia, hand-foot syndrome, immune related adverse events (including interstitial lung disease, AST/ALT elevations, hypothyroidism and hyperthyroidism,etc) and hyper-progressive tumor.
Measured: 1 month after the last date of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2019
- Study start17 Dec 2018
- Primary completion1 Dec 2021
- Study completion30 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Biliary Tract CancerStudies of the same condition, open and under way.
- More trials run by Shanghai Zhongshan HospitalThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shanghai Zhongshan Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Shanghai Junshi Bioscience Co., Ltd., OrigiMed
- Responsible party
- Principal investigator, Tianshu Liu, Shanghai Zhongshan Hospital
- Investigators
- Tianshu Liu, Doctor, Principal investigator, Shanghai Zhongshan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03796429
- Sponsor's protocol ID
- JS001-ZS-BC001
- Status last verified
- Nov 2023
- First submitted
- 4 Jan 2019
- Last updated
- 29 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-arm, Single-center, Prospective Clinical Study of the Efficacy and Safety of Chemotherapy Combined With Toripalimab in the Treatment of Advanced Biliary Tract Cancer
- ClinicalTrials.gov ID
- NCT03796429
- Acronym / sponsor ID
- JS001-ZS-BC001
- Conditions
- Biliary Tract Cancer
- Keywords
- Advanced Biliary Tract Cancer, PD-1 antibody(Toripalimab), first-line chemotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Shanghai Zhongshan HospitalUniversity, hospital or other
- Collaborators
- Shanghai Junshi Bioscience Co., Ltd., OrigiMed
- Study start
- 17 Dec 2018 (actual)
- Primary completion
- 1 Dec 2021 (actual)
- Study completion
- 30 Mar 2022 (actual)
- First posted
- 8 Jan 2019 (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.
- Target population: patients with advanced biliary tract cancer (including gallbladder carcinoma, intrahepatic and extrahepatic cholangiocarcinoma) .
- Primary objective: progression free survival (PFS)/ overall survival (OS) of first-line chemotherapy plus PD-1 antibody (Toripalimab) in patients with advanced biliary tract cancer.
Secondary objectives:
- objective response rate (ORR) of first-line chemotherapy plus PD-1 antibody (Toripalimab)
- safety of first-line chemotherapy plus PD-1 antibody (Toripalimab)
3.Trial design: This is a monocenter, single arm, phase II study to evaluate the efficacy and safety of first-line chemotherapy plus PD-1 antibody (Toripalimab) in patients with advanced advanced biliary tract cancer.
4.Treatment plan: Patients will be given treatment as below once recruited: PD-1 antibody Toripalimab（240mg, iv, q3w），combined with GS regimen(gemcitabine 1000mg／m2 ，d1,d8 + S1 40-60mg bid*14d，Q21d).
The treatment will be continued until emerging of disease progression or intolerable adverse effects (The upper time limit for treatment is 2 years).
5.Number of subjects: 40 patients. Number of centers: 1 sites ( Fudan University Affiliated Zhongshan Hospital).
Detailed description
Backgrounds:
Toripalimab (JS-001) is a PD-1 antibody developed by Shanghai Jun Shi Biomedical technology Co. Ltd. Nowadays, eighteen clinical trials of this drug have been conducted in patients with different types of advanced malignant tumor. Until now, Toripalimab has exhibited favorable safety in recruited patients. Incidence rate of SAE is 14.7%. JS001-Ib-CRP-1.0 is a phase Ib/II basket trial, aiming at evaluating safety and efficacy of JS001 in treating advanced gastric adenocarcinoma, esophageal squamous cell carcinoma, nasopharyngeal carcinoma and head and neck squamous cell carcinoma.The interim analyses results of 161 patients show that the ORR is 22.4%.
Now, the standard chemotherapies regimen for advanced biliary tract cancer include gemcitabine, platinum and fluorouracil; Considering the synergistic effect of chemotherapy and immune therapy, the investigators choose GS regimen (gemcitabine+S1) to combine Toripalimab.
the investigators will shut down the study in advance, if unpredicted SAE or low efficacy occur.
Patients with abnormal autoimmune status, unfavorable body function, factors impeding drug taking, absorption and metabolism will be excluded. Study participants with disease progression or severe/ intolerant toxicity during treatment will withdraw the study.
Hyper-progressive disease is defined as 1) progression 2) more than doubled growth rate 3) tumor volume increase >50% in 2 months after initialing the treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GS+Toripalimab | Experimental | Drug: GS+Toripalimab |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Male or female. Age ≥ 18 years and ≤75 years.
- histologically documented advanced biliary duct cancer, including gallbladder cancer, intrahepatic and extrahepatic cholangiocarcinoma, specimen within a year available for test (at least 10 pathological sections) .
- at least one measurable lesion in abdominal CT/MRI according to RESIST 1.1 is required.
- Karnofsky score≥ 80.
- Adequate hematological function: Neutrophil count ≥ 1.5 × 109/L, Platelets ≥ 100 × 109/L and Hemoglobin ≥90g/L.
Key exclusion criteria (30 listed)
- history of chemo, radiation, immune therapy or radical resection for the biliary tract cancer, except those patients who relapsed after 6 months since the last time of adjuvant therapy.
- patients with active autoimmune disease or history of refractory autoimmune disease.
- patients with active malignant tumor in recent 2 years, except the tumor studied in this research or cured locally tumor like resected basal cell or squamous cell skin cancer, superficial bladder cancer, cervical or breast carcinoma in situ.
- uncontrollable pleural effusion, pericardial effusion, or ascites in 2 weeks before recruitment.
- patients who have digestive tract bleeding in 2 weeks before recruitment or with high risk of bleeding.
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 |
|---|---|---|
| GS+ToripalimabPatients will be given treatment as below once recruited: PD-1 antibody Toripalimab（240mg, iv, q3w），combined with GS regimen(gemcitabine 1000mg／m2 ，d1,d8 + S1 40-60mg bid*14d，Q21d). The treatment will be continued until emerging of disease progression or intolerable adverse effects (The upper time limit for treatment is 2 years). | Drug | GS+Toripalimab |
Primary outcome
progression free survival (PFS) of GS regimen plus PD-1 antibody (Toripalimab)
Time frame: 36 months after the last subject participating in
PFS is defined as time interval from recruitment to tumor progression or censoring. Tumor progression is defined as below: 1) relapse of primary lesion 2) emerging of new lesion 3) distant metastasis 4) death of any reason 5)tumor progression according to RESIST 1.1 on CT/MRI.
overall survival (OS) of GS regimen plus PD-1 antibody (Toripalimab)
Time frame: 36 months after the last subject participating in
OS is defined as time interval from recruitment to all-caused death or censoring.
2 secondary outcomes
objective response rate (ORR) of GS regimen plus PD-1 antibody (Toripalimab)
Time frame: 36 months after the last subject participating in
Incidence of adverse Events of GS regimen plus PD-1 antibody (Toripalimab)
Time frame: 1 month after the last date of treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2023.
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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. This study is not recruiting at the moment.
Tianshu Liu, Doctor principal investigator
Shanghai Zhongshan Hospital
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 GS+Toripalimab in people with Biliary Tract Cancer, run by Shanghai Zhongshan Hospital 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 13 inclusion and 30 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: finished, as of the sponsor's last update on 29 Nov 2023. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
progression free survival (PFS) of GS regimen plus PD-1 antibody (Toripalimab) (time frame: 36 months after the last subject participating in). 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?
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 Nov 2023.