Envafolimab Combined With Recombinant Human Endostatin and First-line Chemotherapy Treat of Advanced Mucosal Melanoma

NCT ID: NCT06041724

Last Updated: 2023-09-18

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-18
• Study Completion Date: 2026-03-18

Brief Summary

This is a phase II, open, single-center study to explore the efficacy and safety of Envafolimab combined with recombinant human endostatin, temozolomide and cisplatin in the treatment of mucosal melanin. At the same time, the tissue and peripheral blood samples of the patients were taken for the determination of PD-L1 expression, ctDNA and other biomarkers and the results were analyzed to find the predictive factors of prognosis or curative effect. Patients with advanced mucosal melanoma who met the inclusion criteria but did not meet the exclusion criteria were enrolled in this study and received 6 cycles of Envafolimab combined with recombinant human endostatin, temozolomide and cisplatin. Patients without progression were then maintained with Envafolimab combined with recombinant human endostatin until disease progression, intolerable adverse reactions, patient death or withdrawal of informed consent. The longest administration time of recombinant human endostatin was no more than 1 year, and that of Envafolimab was not more than 2 years. The efficacy was evaluated for the first time at 6 weeks, every 6 weeks for the following year, and then every 12 weeks until the end of progress or treatment. The examination method was consistent with the baseline; it was expected to be included in the group for 18 months, and clinical observation until disease progression and patient death.

Conditions

Advanced Mucosal Melanoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Envafolimab combined with recombinant human endostatin and first-line chemotherapy

Group Type: EXPERIMENTAL

Envafolimab combined with recombinant human endostatin and first-line chemotherapy

Intervention Type: DRUG

Envafolimab: 300mg day1, s.c. Q3W; Recombinant human endostatin: 210mg day1, Intravenous pump for 72 hours, Q3W; Temozolomide: 150 mg/m2 d1-5, i.v. Q3W; Cisplatin: 25 mg/m2 d1-3, i.v. Q3W.

All of the above drugs were used for 6 cycles, and then Envafolimab and recombinant human endostatin continued only in patients with no progression in the first stage until disease progression as defined by RECIST1.1, unacceptable toxicity, withdrawal from the study or death, or no more than 2 years.

Interventions

Envafolimab combined with recombinant human endostatin and first-line chemotherapy

Envafolimab: 300mg day1, s.c. Q3W; Recombinant human endostatin: 210mg day1, Intravenous pump for 72 hours, Q3W; Temozolomide: 150 mg/m2 d1-5, i.v. Q3W; Cisplatin: 25 mg/m2 d1-3, i.v. Q3W.

All of the above drugs were used for 6 cycles, and then Envafolimab and recombinant human endostatin continued only in patients with no progression in the first stage until disease progression as defined by RECIST1.1, unacceptable toxicity, withdrawal from the study or death, or no more than 2 years.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years old, regardless of gender.
• Histology and pathology confirmed advanced mucosal melanoma.
• Gene mutation state is not limited, except BRAFV600 mutation.
• Has not received first-line treatment for advanced melanoma, and temozolomide and cisplatin have been used in the adjuvant therapy phase, except that the adjuvant therapy phase has been over 6 months or more.
• Eastern Cancer Cooperation Group (ECOG) physical condition score (PS) 0-1.
• The estimated survival time is more than 3 months.
• Within 7 days before screening (including 7 days), the laboratory data were required as follows: neutrophil count ≥ 1.5 × 109 shock L, platelet count ≥ 90 × 109 shock L, hemoglobin ≥ 90g/L (no blood transfusion within 14 days), serum total bilirubin ≤ 1.25x normal upper limit (ULN), ALT and AST ≤ 2.5xULN (patients with liver metastasis ≤ 5xULN); serum creatinine ≤ 1.25xULN.
• Have at least one measurable focus (RECIST1.1 standard).
• Subjects (or their legal representatives / guardians) must sign an informed consent form indicating that they understand the purpose of the study, understand the necessary procedures for the study, and are willing to participate in the study.

Exclusion Criteria

• Patients who have previously used PD-L1 inhibitors, except those who progressed 1 year after the end of adjuvant therapy of PD-L1 monoclonal antibody;
• Allergic to Envafolimab or recombinant human endostatin and experimental chemotherapeutic drugs;
• Received any experimental drugs or antineoplastic drugs within 4 weeks before entering the group;
• There is a risk of bleeding, bleeding events of clinical significance or other taboos in the use of antivascular drugs;
• There is a history of other tumors in the past five years, except for cured cervical cancer or skin basal cell carcinoma;
• There are tumor emergencies that require immediate radiotherapy, such as symptomatic brain or meningeal metastasis, bone-related events, etc;
• Pregnant or lactating women; Fertile women who do not use adequate contraception;
• Alcohol or drug addiction;
• Patients with active, or history of autoimmune diseases that may recur (e.g. systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis, vasculitis, glomerulonephritis, etc.), or patients at high risk (such as immunosuppressive therapy required for organ transplants). Except for autoimmune hypothyroidism that requires only hormone replacement therapy or skin diseases that do not require systemic treatment;
• Patients who need to receive systemic corticosteroids (dose equivalent to > 10mg prednisone / day) or other immunosuppressive drugs within 14 days before enrollment or during the study. The use of topical or inhaled corticosteroids, or short-term (≤ 7 days) use of glucocorticoids for the prevention or treatment of non-autoimmune and infrequent allergic diseases;
• Important organ failure or other serious diseases, including interstitial pneumonia, clinically related coronary artery disease, cardiovascular disease or myocardial infarction, congestive heart failure, unstable angina pectoris, symptomatic pericardial effusion or unstable arrhythmia within 6 months before admission;
• A history of human immunodeficiency virus infection, or other acquired, congenital immunodeficiency diseases, or a history of organ transplant or stem cell transplantation;
• Patients with active chronic hepatitis B or active hepatitis C. HBV carriers, stable hepatitis B (DNA titer ≤ 103copies / ml) and cured hepatitis C patients (HCVRNA negative) can be enrolled in the group;
• A history of severe neurological or psychiatric illness; severe infection; active disseminated intravascular coagulation or other concomitant diseases that, in the opinion of the researchers, seriously endanger the safety of patients or affect the completion of the study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Zhiguo Luo, MD, PhD

Professor and Chief Surgeon

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zhiguo Luo, M.D

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Central Contacts

Zhiguo Luo, M.D

Role: CONTACT

luozhiguo88@163.com

+8621-64175590 ext. 8908

Other Identifiers

Fudan-MM003

Identifier Type: -

Identifier Source: org_study_id