Clinical trial NCT06013943: Envafolimab Combined With GEMOX in First-line Treatment of Advanced GBC
Official title: Envafolimab Combined With GEMOX in First-line Treatment of Advanced Gallbladder Cancer : A Single Center, Single Arm, Phase II Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Gallbladder Cancer
Keywords: Envafolimab(immune checkpoint inhibitor anti-PD-L1 antibody)
Lead sponsor: Eastern Hepatobiliary Surgery Hospital
Sponsor class: OTHER
First posted: 2023-08-28
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The TOPAZ-1 study compared the advantages and disadvantages of immune checkpoint inhibitor anti-PD-L1 antibody combined with Gem/Cis chemotherapy (Gemcitabine and Cisplatin) and Gem/Cis chemotherapy alone in first-line treatment of advanced biliary tract tumors (BTC, which including gallbladder cancer). It was observed that chemotherapy combined with PD-L1 antibody improved progression-free survival (PFS) and overall survival (OS).

As a standard first-line chemotherapy regimen for BTC too, Gemox chemotherapy (gemcitabine and cisplatin) has a median OS of 9.5 months, and non-inferior survival time to Gem/Cis chemotherapy. In addition, Gemox chemotherapy has been widely used in clinical practice because it reduces the requirement on patients' renal function and has good tolerance. Envafolimab is a novel fusion of humanized mono-domain PD-L1 antibody and human IgG Fc fragment, which has shown good efficacy and safety in a variety of solid tumors. It is safe and convenient to administer by subcutaneous injection. However, there is currently no clinical data on Envafolimab combined with GEMOX chemotherapy in patients with advanced gallbladder cancer (GBC).

The goal of this clinical trial is to evaluate its efficacy and related safety in patients with GBC. Eligible participants will receive Envafolimab (up to 12 months) plus gemcitabine and cisplatin (up to 6-8 cycles) until progression of radiological disease, unacceptable toxicity, or withdrawal from the study, whichever comes first.The primary endpoint was the 6-month PFS rate.


Eligibility criteria: Inclusion Criteria:

1. Definite diagnosis of gallbladder carcinoma by histology or cytology；
2. There is at least one measurable lesion (according to RECIST1.1);
3. From 18 to 75 years old, ECOG physical strength score of 0-2;
4. Basically normal bone marrow function: neutrophils \>1.5x10\^9/L, platelets \>100x10\^9/L;
5. Adequate renal function: creatinine clearance \> 60ml/min;
6. Adequate liver function: bilirubin ≤1.5ULN;
7. No cardiac insufficiency or chest pain (medically uncontrollable); No myocardial infarction in the 12 months prior to study initiation;
8. Estimated survival time ≥3 months;
9. The patient must sign an informed consent form.

Exclusion Criteria:

1. Previous systematic therapy, including chemotherapy, immunotherapy and targeted therapy;
2. Secondary malignancies or other neoplasms (except superficial skin cancer and localized low-grade malignancies) occurring in the 3 years prior to study initiation;
3. The presence of brain or meningeal metastasis;
4. Have active or previously recorded autoimmune or inflammatory diseases (eg Rheumatoid arthritis, psoriasis, systemic lupus erythematosus, AIDS, etc. );
5. Have received allogeneic organ transplantation (eg kidney transplantation, liver transplantation, heart transplantation, etc. );
6. Patients who need long-term oral hormone therapy due to their underlying diseases;
7. Patients with interstitial pneumonia and autoimmune hepatitis;
8. Inflammatory infections during the active period of infection or other patients who may have disabilities receive planned treatment;
9. Persons with a history of uncontrolled substance abuse or mental disorders;
10. Patients with concomitant diseases that, in the judgment of the investigator, may seriously endanger their own safety or may interfere with the completion of the study;
11. Patients with poor renal function;
12. Untreated complete/incomplete ileus that prevents eating or interferes with systemic administration;
13. Participated in other clinical trials;
14. Pregnant and lactating women.

Primary outcomes:
measure: 6-month progression-free survival rate (PFS)
timeFrame: 6 months
Secondary outcomes:
measure: Progression free survival (PFS)
timeFrame: Up to two years
measure: Overall survival (OS)
timeFrame: Up to two years
measure: Disease control rate (DCR) per RECIST 1.1
timeFrame: Once every 3 weeks (±7 days) from the first day of Envafolimab treatment for a maximum of 2 years until confirmed objective disease progression, death, and study termination.
measure: Objective response rate (ORR) per RECIST 1.1
timeFrame: Once every 3 weeks (±7 days) from the first day of Envafolimab treatment for a maximum of 2 years until confirmed objective disease progression, death, and study termination.
Other outcomes:
measure: Tumor markers
timeFrame: Once every 9 weeks (±7 days) from the first day of Envafolimab treatment for a maximum of 2 years until confirmed objective disease progression, death, and study termination.
measure: Lymphocyte count
timeFrame: Once every 9 weeks (±7 days) from the first day of Envafolimab treatment for a maximum of 2 years until confirmed objective disease progression, death, and study termination.
measure: Adverse events
timeFrame: Envafolimab treatment is performed once per cycle (±7 days), and the last one is completed within 30 days (±3 days) after ending treatment or before starting a new anti-tumor therapy.
Locations:
city: Shanghai
country: China
facility: Easter hepatobiliary surgery hospital
state: Shanghai
Study officials:
affiliation: Eastern Hepatobiliary Surgery Hospital, Navy Medical University
name: Zhengang Yuan, PhD
role: PRINCIPAL_INVESTIGATOR
References: