A Safety and Efficacy Study of Surufatinib Combination With Toripalimab in Patients With Recurrent Biliary Tract Cancer

A Safety and Efficacy Study of Surufatinib Combination With Toripalimab in Patients With Recurrent Biliary Tract Cancer : a Phase Ⅱ Study

A Phase Ⅱ, open-label, single-arm study to assess the safety, tolerability, and efficacy of Surufatinib Combination With Toripalimab in Patients With Recurrent Biliary Tract Cancer.

Study Overview

• Status: Recruiting
• Conditions: Biliary Tract Cancer
• Intervention / Treatment: Drug: Surufatinib Toripalimab

Detailed Description

A Phase 2, open-label, single-arm study to assess the safety, tolerability, and efficacy of Surufatinib Combination With Toripalimab in Patients With Recurrent Biliary Tract Cancer (intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer).

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Renhao Wang, MD; Phone Number: 13605207887; Email: wangrenhao@126.com
• Study Contact Backup: Name: Bin Zhang, MD; Phone Number: 15252039221; Email: zhangbin@xzhmu.edu.cn

Study Locations

• China
  • Jiangsu
    • Xuzhou, Jiangsu, China
      • Recruiting
      • The Affiliated Hospital of Xuzhou Medical University
      • Contact: Renhao Wang, MD; Phone Number: 13605207887; Email: wangrenhao@126.com
      • Principal Investigator: Bin Zhang, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male and Female aged between 18 and 75 years are eligible; Provision of written Informed Consent Form (ICF) prior to any study specific procedures;
2. Advanced (unresectable) or metastatic biliary carcinomas that have been histologically or cytologically confirmed include intrahepatic or extrahepatic carcinoma of the bile duct, carcinoma of the gallbladder, and carcinoma of the ampullary of fatt, and have been histologically confirmed as adenocarcinoma;
3. Patients who have previously received disease progression or toxic side effects after first-line systemic chemotherapy are not tolerated;The standard first-line chemotherapy regimen was defined as a two-drug combination regimen of gemcitabine plus cisplatin, gemcitabine plus gio, or capecitabine plus oxaliplatin.Failure of first-line standard chemotherapy was defined as progression of disease during treatment or within 6 months after the last treatment;Or the toxic side effects of the treatment process are intolerable;
4. Presence of at least one measurable target lesion for further evaluation according to RECIST criteria;
5. Patients who had previously received A VEGF or VEGFR-targeted drug required progression 4 months after the last dose;
6. No systemic antitumor therapy in 4 weeks;
7. The patient has no evidence of biliary obstruction unless the obstruction is controlled by local treatment or the patient is decompressed by endoscopic or percutaneous stenting, and bilirubin is subsequently reduced to below the upper limit of 1.5x normal (ULN);
8. Eastern Cooperative Oncology Group (ECOG) performance status 0-1;Predicted survival ≥3 months;

9. Screening laboratory values must meet the following criteria (within past 14 days):

   • neutrophils ≥1.5×109/L ;
   • platelets ≥9g/dL；
   • hemoglobin ≥ 9.0 g/dL;
   • albumin≥3g/dL；
   • total bilirubin ≤ 1.5 x upper limit of normal (ULN); aspartic transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN without, and ≤ 5 x ULN with hepatic metastasis; serum creatinine ≤1.5╳ULN;
10. Voluntary enrollment, good compliance, can cooperate with the experiment observation, and signed a written informed consent;
11. Males or female of childbearing potential must: agree to use using a reliable form of contraception (eg, oral contraceptives, intrauterine device, control sex desire, double barrier method of condom and spermicidal) during the treatment period and for at least 6 months after the last dose of study drug.

Exclusion Criteria:

1. Prior treatment with Surufatinib,or other antiangiogenic drugs were used within 6 months;
2. Prior antitumor therapy with chemotherapy, radical radiation therapy ，biological immunotherapy，targeted therapy within 4 weeks.
3. Prior participation in other clinical trials not approved or listed in China within past 4 weeks；
4. Prior major surgery within past 4 weeks (diagnostic surgery excluded);
5. International standardized ratio (INR) >1.5 or partially activated prothrombin time (APTT) >1.5×ULN;
6. Clinically significant severe electrolyte abnormality judged by investigator ;
7. Hypertension that is not controlled by the drug, and is defined as: SBP≥140 mmHg and/or DBP≥90 mmHg;
8. Currently suffering from poorly controlled diabetes (after regular treatment, fasting plasma glucose concentration ≥10mmol/L);
9. The patient currently has disease or condition that affects the absorption of the drug, or the patient cannot be administered orally;
10. Digestive tract disease such as gastric and duodenal active ulcer, ulcerative colitis or unresected tumor, or other conditions determined by the investigator that may cause gastrointestinal bleeding and perforation;
11. Evidence of bleeding tendency or history within 3 months, or thromboembolic event (including a stroke event and/or a transient ischemic attack) occurred within 12 month;
12. Cardiovascular disease of significant clinical significance (myocardial infarction, unstable arrhythmia or unstable angina ，Coronary Artery Bypass Grafting within past 6 months,)；
13. Had other malignant tumors in the past 5 years (except for basal cell carcinoma or squamous cell carcinoma, cervical carcinoma in situ that have been effectively controlled);
14. Active or uncontrolled severe infection (≥CTCAE2 infection);
15. Positive tests for HIV, HCV, HBsAg or HBcAb with positive test for HBV DNA (>2000IU/ml);
16. Evidence with active CNS disease or previous brain metastases;
17. The toxicity associated with previous anti-tumor treatment has not recovered to ≤CTCAE1, except for peripheral neurotoxicity and alopecia ≤CTCAE2 caused by oxaliplatin;
18. Pregnant or nursing;
19. Transfusion therapy, blood products and hematopoietic factors, such as albumin and granulocyte colony stimulating factor (G-CSF), had been received within 14 days before enrollment;
20. Tumor involving skin and/or pharyngeal mucosa with ulceration;
21. Patients with a history of psychotropic drug abuse and unable to quit or with mental disorders;
22. Any other disease, with clinical significance of metabolic abnormalities, abnormal physical examination or laboratory abnormalities, according to researchers, there is reason to doubt is not suitable for the use of study drugs in patients with a disease or condition (such as have a seizure and require treatment), or will affect the interpretation of results, or make the patients at high risk.
23. Routine urine indicated that urine protein ≥2+, and the 24-hour urine protein volume >1.0g;
24. Underlying medical condition that, in the Investigator's opinion, would increase the risks of study drug administration or obscure the interpretation of toxicity determination or adverse events.
25. Prior receipt of any anti-PD-1 /PD-L1/PD-L2 antibody or anti-cytotoxic T lymphocyte associated antigen-4 (CTLA-4) antibody or any other antibody acting on T cell co-stimulation or checkpoint pathway (e.g. OX40, CD137, etc.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Biliary Tract Cancer; Surufatinib 250mg/Toripalimab 240mg	Drug: Surufatinib Toripalimab; Surufatinib at a dose of 250mg Qd, with humanized anti-PD-1 monoclonal antibody Toripalimab injected intravenously 240mg per 3 weeks until disease progresses or unacceptable tolerability occurs.; Other Names: Surufatinib/JS001

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate(ORR)	The number of cases in which tumor size is reduced to PR or CR / the total number of evaluable cases (%). In the event of PR or CR, the subjects should confirm it no less than 4 weeks after the first evaluation. CT/MRI will be performed every 2 cycles of treatment by RECIST 1.1(each cycle is 21 days))	up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	To assess the efficacy of Surufatinib Combination With Toripalimab in Patients With Recurrent Biliary Tract Cancer, patients by assessment of progression free survival (PFS) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).	up to 12 months
Overall survival (OS)	The time interval between the start date of study drug and the date of death (any cause).	up to 36 months

Collaborators and Investigators

• Sponsor: The Affiliated Hospital of Xuzhou Medical University
• Investigators: Principal Investigator: Renhao Wang, MD, The Affiliated Hospital of Xuzhou Medical University; Principal Investigator: Bin Zhang, MD, The Affiliated Hospital of Xuzhou Medical University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2021
• Primary Completion (Anticipated): June 1, 2022
• Study Completion (Anticipated): June 1, 2024

Study Registration Dates

• First Submitted: September 15, 2021
• First Submitted That Met QC Criteria: September 15, 2021
• First Posted (Actual): September 24, 2021

Study Record Updates

• Last Update Posted (Actual): December 27, 2021
• Last Update Submitted That Met QC Criteria: December 22, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Biliary Tract Diseases; Biliary Tract Neoplasms
• Other Study ID Numbers: HMPL-012-SPRING-B101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No