Envafolimab Combined With GEMOX in First-line Treatment of Advanced GBC

Gallbladder Cancer Clinical Trial

Official title:

Envafolimab Combined With GEMOX in First-line Treatment of Advanced Gallbladder Cancer : A Single Center, Single Arm, Phase II Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06013943
• Other study ID #: EHBHKY2022-H040-P001
• Status: Recruiting
• Phase: Phase 2
• Start date: March 17, 2023
• Est. completion date: December 2025

Study information

• Verified date: September 2023
• Source: Eastern Hepatobiliary Surgery Hospital
• Contact: Zhengang Yuan, PhD
• Phone: +86-021-81887453
• Email: yuanzg[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 2025
• Est. primary completion date: May 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Gallbladder Cancer
• Gallbladder Neoplasms

Intervention

Drug:
• Envafolimab+Gemox
All of drugs were used for 6-8 cycles at the combined treatment stage, then Envafolimab and Gemcitabine continued at maintenance treatment stage until disease progression as defined by RECIST1.1, unacceptable toxicity, withdrawal from the study or death, or no more than 1 years. Combined treatment stage: Envafolimab(150mg, iH, Q1W, Day1)+Gemcitabine(1000mg/m2, iv, Q3W, Day1 and Day8)+Cisplatin(1000mg/m2, iv, Q3W, Day1 and Day8); Caintenance treatment stage: Envafolimab(400mg, iH, Day1, Q3W)+Gemcitabine(1000mg/m2, po, Day1-14, Q3W).

Locations

Country	Name	City	State
China	Easter hepatobiliary surgery hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Eastern Hepatobiliary Surgery Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Tumor markers	The peripheral blood samples of the patients were taken for the determination of tumor-associated Macrophages(TAMs)expression, and the results were analyzed to explore the effect of oxaliplatin on immune remodeling.	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.
Other	Lymphocyte count	Detecting the changes of lymphocyte count to conform the effect of oxaliplatin on tumor immune remodeling.	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.
Other	Adverse events	Defined as the incidence of treatment emerge adverse events, treatment related adverse events and serious adverse events.	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.
Primary	6-month progression-free survival rate (PFS)	Defined as the rate of patients had no disease progression or death (whichever occurred first) from the start of treatment to 6 months after treatment.	6 months
Secondary	Progression free survival (PFS)	Defined as the time from the start of treatment to the date of progressive disease, or death, whichever occurred first.	Up to two years
Secondary	Overall survival (OS)	Defined as the time from the start of treatment to the date of death from any cause.	Up to two years
Secondary	Disease control rate (DCR) per RECIST 1.1	Defined as patients achieving a complete response [CR] or partial response [PR] or stable disease [SD].	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.
Secondary	Objective response rate (ORR) per RECIST 1.1	Defined as patients achieving a complete response [CR] or partial response [PR].	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.