Advanced Primary Liver Cancer, Advanced Biliary Tract Carcinoma
Conditions
Brief summary
This an open-label，Non-Randominzed Phase 2 study to evaluate the Safety and Tolerability of SHR-1210 in combination with Apatinib or chemotherapy (FOLFOX4 or GEMOX regimen) in subjects with Advanced PLC.or BTC Participants with advanced PLC who failed or intolerable to prior systemic therapy will be treated with SHR-1210 plus Apatinib; Participants with advanced PLC or BTC who have never received prior systemic therapy will be treated with SHR-1210 plus FOLFOX4 or GEMOX regimen.
Interventions
Sponsors
Jiangsu HengRui Medicine Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Histologically confirmed advanced PLC or advanced BTC (including bile duct carcinoma and gallbladder carcinoma) ; not suitable to surgery or local regional treatment; with at least one measurable lesion per RECIST 1.1. 2. Arm A:Failed or intolerable to at least one prior systemic treatment for advanced PLC. Arm B:No previous systemic treatment for advanced PLC or BTC 3. ECOG Performance Status of 0 or1. 4. Child-Pugh Class A or B with 7 points . 5. Life Expectancy of at least 12 weeks. 6. Has controlled infection by Hepatitis B Virus (HBV DNA\<500 IU/ml) or Hepatitis C Virus. 7. Adequate organ function. 8. Male or female participants of childbearing potential must be willing to use an adequate method of contraception starting with the first dose of study drug through 60 days for female subjects and 120 days for male subjects after the last dose of study drug. 9. Patient has given written informed consent.
Exclusion criteria
1. Known fibrolamellar HCC; Prior malignancy active with the previous 5 years except for locally curable cancers that have been apparently cured. 2. Known or occurrence of central nervous system (CNS) metastases. 3. Ascites with clinical symptoms. 4. Known or evidence of GI hemorrhage within the past 6 months. 5. Known or occurrence of hemorrhage/ thrombus. 6. Known or evidence of abdomen fistula, gastrointestinal perforation, or abdominal abscess within the past 2 months. 7. Suffered from grade II or above myocardial ischemia or myocardial infarction, uncontrolled arrhythmias. 8. Grade III\~IV cardiac insufficiency, according to NYHA criteria or echocardiography check: LVEF\<50%. 9. Hypertension and unable to be controlled within normal level following treatment of anti-hypertension agents (systolic blood pressure \> 140mmHg, diastolic blood pressure \> 90 mmHg). 10. Factors to affect oral administration (such as patients unable to swallow oral medications, chronic diarrhea and ileus etc. situations evidently affect drug oral medication and absorption). 11. History of hepatic encephalopathy. 12. Known history of human immunodeficiency virus (HIV) infection. 13. Active infection or an unexplained fever \> 38.5°C during screening visits. 14. Has received a live vaccine within 30 days. 15. Prior or planning to organ transplantation including liver transplantation. 16. Interstitial lung disease that is symptomatic or may interfere with the detection and management of suspected drug-related pulmonary toxicity. 17. Proteinuria≥ 2+ or 24 hours total urine protein \> 1.0 g. 18. Active known, or suspected autoimmune disease. 19. Subjects with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first administration of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses \> 10 mg daily. prednisone equivalent, are permitted in the absence of active autoimmune disease 20. Any loco-regional therapy to liver (included but not limited: resection, radiotherapy, TAE, TACE, TAI, RFA or PEI) within 4 weeks prior to study. 21. Prior therapy with anti-PD-1 or other anti-PD-1/anti-PD-L1 immunotherapy. 22. Known history of hypersensitivity to monoclonal antibodies or any components of the study drugs. 23. Treatment with anti-coagulation therapy(Warfarin or heparin) or anti-platelet therapy(aspirin at dose≥300mg/day, clopidogrel at dose≥75mg/day). 24. Pregnant or breast-feeding women. 25. According to the investigator, other conditions that may lead to stop the research.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Safety and Tolerability | Up to approximately 4 years | The incidence of adverse events (AEs) and Serious adverse events (SAEs) assessed by NCI-CTCAE v4.03 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to approximately 4 years | Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) assessed by investigator: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
| Duration of Response (DoR) | Up to approximately 4 years | The time from the date of the first recorded objective tumor response (assessed as per RECIST V1.1) to the date of the first recorded objective tumor progression (assessed as per RECIST V1.1) or the date of death due to any cause, whichever occurs first, in subjects with a BOR of CR or PR. |
| Disease Control Rate (DCR) | Up to approximately 4 years | The percentage of subjects with a BOR of CR, PR, and SD as per RECIST V1.1. BOR of CR or PR must be confirmed at least 4 weeks (28 days) after the initial assessment. |
| Time to Progression (TTP) | Up to approximately 4 years | The time from the date of the first dose to the date of radiographic PD (assessed by the investigator as per RECIST V1.1).PD is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or significant progression of non-target lesions leading to discontinuation of therapy, or the appearance of new lesions. |
| Overall Survival | Up to approximately 4 years | The time from the date of the first dose to death due to any cause. Overal Survial will be calculated based on Kaplan-Meier estimates |
| Time to Response (TTR) | Up to approximately 4 years | The time from the date of the first dose to the date of the first recorded tumor response (assessed as per RECIST V1.1) in subjects with a BOR of CR or PR. |
| Progression-free Survival (PFS) | Up to approximately 4 years | The time from the date of the first dose to the date of the first recorded tumor progression (assessed as per RECIST V1.1) or the date of death due to any cause, whichever occurs first. |
Countries
China
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 52.9 years STANDARD_DEVIATION 9.54 |
| Race and Ethnicity Not Collected | 0 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 11 / 28 | 11 / 34 | 35 / 92 | 1 / 3 |
| other Total, other adverse events | 28 / 28 | 34 / 34 | 92 / 92 | 3 / 3 |
| serious Total, serious adverse events | 14 / 28 | 20 / 34 | 58 / 92 | 2 / 3 |
Outcome results
None listed