Interferon-α1b Combined With Toripalimab and Anlotinib Hydrochloride in Advanced Unresectable Melanoma

Trial details

Who runs it

Xijing Hospital

Trial code

NCT05539118

Record updated

14 September 2022

Original description

The purpose of this study is to evaluate the efficacy and safety of recombinant human interferon-α1b (IFN-α1b) combined with toripalimab and anlotinib hydrochloride in patients with unresectable advanced melanoma. This study consists of 2 phases（ Ib / II）. Phase Ib will determine the recommended phase Ⅱ dose for anlotinib hydrochloride. Phase II will evaluate the efficacy and safety of the triple combination regimens.Read full original descriptionShow less

Interferon-α1b (IFN-α1b) Combined With Toripalimab and Anlotinib Hydrochloride in Patients With Advanced Unresectable Melanoma

The purpose of this study is to evaluate the efficacy and safety of recombinant human interferon-α1b (IFN-α1b) combined with toripalimab and anlotinib hydrochloride in patients with unresectable advanced melanoma. This study consists of 2 phases（ Ib / II）. Phase Ib will determine the recommended phase Ⅱ dose for anlotinib hydrochloride. Phase II will evaluate the efficacy and safety of the triple combination regimens.

Inclusion: Aged 18-75; ECOG performance status of 0 or 1; Life expectancy ≥ 3 months; Histologically or cytologically confirmed diagnosis of unresectable stage IIIc, IIId and IV melanoma by the American Joint Committee on Cancer (AJCC) (the 8th Edition). (Note: uveal melanoma cases are excluded); Baseline tumor specimens available for NGS analysis or equivalent test results acceptable by the principal investigator; Measurable disease by RECIST v1.1 criteria; Adequate organ and marrow function (within 4 weeks prior to study treatment initiation):; A negative urine or plasma β-HCG test result is required at screening for female patients of childbearing potential; Contraception is required for patients and their partners throughout the trial and within 1 year after the last dose of study treatment; Capable of understanding and complying with the study protocol requirements ( including follow-up visit and examinations); Be willing to signed a written informed consent document before enrollment.

Exclusion: Patients accepted other anti-tumor clinical trials within 4 weeks prior to study entry; Patients accepted anti-tumor radiotherapy within 4 weeks prior to study entry; Plan to take other systemic or local anti-tumor therapy during the current study; Systemic treatment with either corticosteroid (> 10 mg /kg prednisone equivalents) or other immunosuppressive medications prior to 2 weeks prior to study dose initiation; Use of anticoagulants or vitamin K antagonists such as warfarin, heparin or similar drugs; Any condition has potential risk of gastrointestinal bleeding or perforation, such as active gastrointestinal ulcer, known intra luminal metastases,inflammatory bowel disease; known abdominal fistula, gastrointestinal perforation or intraperitoneal abscess 4 weeks prior to entry of the study entry; Surgery history within past 4 weeks, except for melanoma removal or partial removal; A history of getting a live vaccine within 4 weeks prior to the first dose; a history of hematopoietic stimulating factor therapy such as colony-stimulating factor (CSF) and erythropoietin (EPO) within 2 weeks prior to the first dose; a history of major surgeon except for diagnosis within 4 weeks prior to the first dose; History of allergic reactions attributed to compounds of similar chemical or biologic composition to recombinant human interferon-α1bcombined, toripalimab and anlotinib hydrochloride; Disease improved by in response to anti-tumor therapies within 4 weeks including perioperative chemotherapy, molecularly targeted therapy, PD-1/PD-L1/CTLA-4 immune therapy, anti-angiogenesis therapy (such as sunitinib, sorafenib, regorafenib, bevacizumab, imatinib, apatinib) or interferon, herbal supplements; Known hematologic malignancy, primary brain tumor, sarcoma or any other primary solid tumor unless the disease-free period is over 5 years; Known severe hypersensitivity reaction of another mono-antibody therapy; Known active autoimmune disease requiring systemic treatment (such as corticosteroids or immunosuppressive medications) or related replacement therapies (such as thyroid hormone for hypothyroidism, insulin for diabetes or physiological glucocorticoid replacement therapy for adrenal or pituitary insufficiency) in the past 2 years; Hereditary or acquired bleeding and thrombotic tendency such as hemophilia, thrombocytopenia, hypersplenism; Uncontrolled hypertension defined as persistent systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg despite antihypertension medicine therapy; Other diseases that may affect compliance or interfere with results interpretation including active opportunistic infections or progressing or severe infections , uncontrolled diabetes or pulmonary diseases including interstitial pneumonia, obstructive pulmonary disease and symptomatic bronchospasm. Known HIV or AIDS-related illness, or active HBV, HCV and tuberculosis; Diagnosis of a psychiatric or substance abuse disorder; Individuals with bleeding tendency or under thrombolytic or anticoagulant therapy. Coagulation abnormalities as the following circumstances: INR >1.5；PT > 1.2 ULN；PTT > 1.2 ULN; Known cardiovascular diseases as follows in the past 6 months (cerebral vascular accident, transient ischemic attack, cardiac arrhythmia（including QTc ≥ 450 ms for males and QTc ≥ 470 ms for females; angina,coronary angioplasty or coronary stent implantation, pulmonary embolism,untreated deep vein thrombosis or anticoagulation treatment less than six weeks,arterial thrombosis; heart failure patients in NYHA class III and IV; above Ⅱ degrees heart block; myocardial infarction unstable arrhythmia, or unstable angina in the past 6 months; cerebral infarction within 3 months; left ventricular ejection fraction (LVEF) is less than 50% and clinically significant pericardial disease indicated by color doppler echocardiography; ECG indicates acute ischemia or active conduction system abnormalities; Use of medications which might lead to Prolonged QT interval and torsades de pointes; Any other illness, laboratory abnormality, or situations that in the opinion of the principal investigator would compromise the patients' ability to tolerate treatment or would limit compliance with study requirements; Imaging confirmed of central nervous system (CNS) metastases with or without meningeal carcinomatosis; Obvious hemoptysis or daily hemoptysis above 2.5ml in the past 2 months; Open wounds, ulcers or fractures; Individuals who are pregnant or breast-feeding or plan to conceive during the study period.

ClinicalTrials.gov NCT05539118