Adebrelimab Combined with Apatinib and Gemcitabine and Cisplatin (GP) First-line Treatment for Unresectable Biliary Tract Carcinoma

Official title

A Prospective, Single Arm Study of Adebrelimab Combined with Apatinib and Gemcitabine and Cisplatin (GP) First-line Treatment for Unresectable Biliary Tract Carcinoma

Overview

This study is designed to combine anti-angiogenic drugs on the basis of PD-L1+ gemcitabine/cisplatin, hoping to further improve the curative effect of advanced BTC treatment and provide more choices for first-line treatment of BTC in China.

Interventions

• Drug Adebrelimab
  adepelizumab ,1200mg, q3w
• Drug Apatinib
  apatinib，250mg，QD
• Drug gemcitabine and cisplatin
  cisplatin 25mg/m2，gemcitabine 1000mg/m2 d1,d8，q3w

Primary outcome measures

• Progression-free Survival [Time frame: From first dose of study intervention until disease progression or death (whichever occurs first), up to approximately 6 months after the last subject enrolled]

Secondary outcome measures (4)

• Overall Survival(OS) [Time frame: From first dose of study intervention until death, at least 12 months after the last subject enrolled]
• Objective Response Rate (ORR) [Time frame: From first dose of study intervention until disease progression or death (whichever occurs first), up to approximately 3 months after the last subject enrolled]
• Duration of Response(DOR) [Time frame: From first dose of study intervention until disease progression or death (whichever occurs first), up to approximately 6 months after the last subject enrolled]
• Incidence of treatment-emergent adverse events(AEs) [Time frame: From first dose of study intervention until 90 days after last dose or death (whichever occurs first)]

Eligibility criteria

Inclusion criteria

• 1.Age range from 18 to 80 years old, regardless of gender;
• 2.Histologically confirmed, unresectable advanced or metastatic BTC including cholangiocarcinoma (intrahepatic or extrahepatic), gallbladder carcinoma.
• 3\. Patients who have not received systematic treatment for BTC in the past .
• 4.At least one measurable lesion (according to RECIST v1.1 requirements).
• 5.ECOG PS: 0-1 points;
• 6.Expected survival time ≥ 12 weeks;
• 7\. The main organs are functioning normally and meet the following requirements White blood cell count ≥ 3.0× 10 9/L; Hb ≥ 90 g/l; Absolute neutrophil count ≥ 1.5× 10 9/L; Platelet count ≥ 100× 10 9/L; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)≤ 2.5 times the upper limit of normal limit (ULN); Total bilirubin ≤ 2 times of ≤ULN; Serum creatinine ≤ 1.5 times of ≤ULN; Albumin ≥ 30 g/l;
• 8\. Women of childbearing age must undergo a pregnancy test (serum or urine) with a negative result within 14 days prior to enrollment, and voluntarily use appropriate methods of contraception during observation and within 8 weeks after the last administration of study medication; For males, surgical sterilization should be performed, or appropriate methods of contraception should be agreed upon during observation and within 8 weeks after the last administration of study medication;
• 9\. The subjects voluntarily joined this study, signed an informed consent form, and cooperated with follow-up.

Exclusion criteria

• 1\. Histologically diagnosed as neuroendocrine carcinoma;
• 2\. People who are allergic to adebelizumab, apatinib, gemcitabine, cisplatin or their auxiliary materials;
• 3\. Systemic treatment in the past;
• 4\. Pleural effusion, pericardial effusion or ascites accompanied by clinical symptoms and judged by the researcher to require frequent drainage;
• 5\. History of organ transplantation (including autologous bone marrow transplantation and peripheral stem cell transplantation);
• 6\. Active or uncontrollable serious infection (≥ CTCAE grade 5.02 infection), including but not limited to hospitalization due to infection complications, bacteremia or severe pneumonia, and unexplained fever > 38.5℃ before the first administration;
• 7\. Liver cirrhosis and active hepatitis; Hepatitis B reference: HBsAg positive, and HBV DNA exceeds the upper limit of normal value (1000 copies /ml or 500 IU/ml); Patients with hepatitis B virus (HBV) infection or cured HBV infection in the past (defined as the existence of hepatitis B core antibody \[HBcAb\] and the absence of HBsAg, and those with normal HBV DNA value during the screening period can be included; Hepatitis C reference: HCV antibody is positive, and the detection value of HCV virus titer exceeds the upper limit of normal value /HCV RNA or HCV Ab detection indicates acute and chronic infection;
• 8\. Those who have a history of psychotropic drug abuse and cannot quit or have mental disorders;
• 9.Within 5 years, the subject has other malignant tumors in the past or at the same time and needs active treatment (except for fully treated basal cell or squamous cell skin cancer, cervical carcinoma in situ and breast cancer in situ, if the estimated 5-year survival rate is more than 90%);
• 10\. There is an uncorrectable coagulation disorder;
• 11\. Severe liver diseases (such as liver cirrhosis), kidney diseases, respiratory diseases, uncontrollable diabetes or other types of systemic diseases.
• 12\. Patients whose imaging shows that the tumor has invaded important blood vessels or who are judged by the researchers to be very likely to invade important blood vessels and cause fatal bleeding during the follow-up study;
• 13\. Active autoimmune disease or immunodeficiency, or the following medical history, including but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, rheumatoid arthritis, inflammatory bowel disease, hypophysitis, vasculitis, nephritis, etc.) shall not be included. The following exceptions are made: patients with a history of autoimmune hypothyroidism but receiving thyroid hormone replacement therapy can be included in the study. Patients with type 1 diabetes whose blood sugar has been controlled after insulin administration can participate in this study.
• 14, Within 14 days prior to signing the informed consent form, use immunosuppressive agents or systemic hormone therapy to achieve immunosuppressive effects (dose>10mg/day prednisone or other therapeutic hormones)
• 15.Arterial/venous thrombosis events occurred within 6 months before the first administration, such as cerebrovascular accident (including temporary ischemic attack, cerebral hemorrhage, cerebral embolism, etc.), deep venous thrombosis and pulmonary embolism;
• 16.The researcher judges digestive tract diseases or conditions that may affect drug absorption, including but not limited to active gastric and duodenal ulcers, ulcerative colitis or active bleeding of unresectable digestive tract tumors, or other conditions that may cause gastrointestinal bleeding or perforation as judged by the researcher, with various factors that affect oral drugs (such as inability to swallow, gastrointestinal resection, chronic diarrhea and intestinal obstruction, etc.);
• 17.Individuals with hypertension who cannot be reduced to the normal range after antihypertensive drug treatment (systolic blood pressure ≥ 150mmHg or diastolic blood pressure ≥ 100mmHg)
• 18.Surgery (except biopsy) was performed within 28 days before being enrolled in this study, or the surgical incision was not completely healed;
• 19.Have received any other experimental drug treatment or participated in other intervention research within 4 weeks before signing the informed consent form;
• 20.Pregnant (pregnancy test positive before medication) or breast-feeding women;
• 21.According to the researcher's judgment, that is not suitable for patients in the group;

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• HeNan — Zhengzhou

Identifiers

NCT: NCT06749730 · BTC-II-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗