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Imatinib and Toripalimab in Patients With Locally Advanced/Metastatic Melanoma Harbored With CKIT Mut

Primary Purpose

Advanced Melanoma

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
JS001+Imatinib mesylate
Sponsored by
Peking University Cancer Hospital & Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age ≥18, no gender limitation;
  2. Patients with recurrent, unresectable or metastatic melanoma confirmed by histopathology after surgery (stage III/IV);
  3. With CKIT gene mutation;
  4. Did not receive CKIT inhibitor or PD-1/PD-L1 mab treatment in late stage; Adjuvant therapy Patients who have received CKIT inhibitors or PD-1/PD-L1 mab should be discontinued for at least 6 months;
  5. ECOG score is 0 or 1;
  6. Expected survival ≥3 months;
  7. The investigator assessed the presence of at least one measurable lesion that had not been irradiated according to RECIST 1.1;
  8. No history of brain/meningeal metastasis;
  9. The organ function level must meet the following requirements (7 days before the first administration of the study drug):

    Spinal cord: Neutrophil absolute count (ANC)≥1.5×109/L, platelet (PLT)≥ 100×109/L, and hemoglobin (HB)≥9g/dL(no blood transfusion or component blood was received within 14 days prior to test); Gallo liver: Serum total bilirubin (TBIL)≤1.5 times the upper limit of normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT)≤2.5 times the upper limit of normal ( allows AST and ALT≤5 times the upper limit of normal if liver metastasis is present); serum creatinine ≤1.5 times the upper limit of normal value and endogenous creatinine clearance ≥50mL/min (Cockcroft-Gault formula); Accidence International standardized ratio (INR), activated partial thrombin time (aPTT)≤1.5 times the upper limit of normal value (only for patients not receiving anticoagulant therapy; Patients receiving anticoagulant therapy should keep the anticoagulant within the therapeutic range); Thyroid stimulating hormone (TSH)≤1×ULN (if abnormal, FT3 and FT4 levels should be investigated simultaneously; if FT3 and FT4 levels are normal, they can be included in the group) Isogenic urinary protein ≤1+, isogenic urinary protein & GT; 1+, urine protein should be collected for 24 hours, and the total amount should be less than or equal to 1 g; Unconsciously the heart functions normally, meaning normal or abnormal ECG has no clinical significance, while cardiac ultrasound shows left ventricular ejection fraction (LVEF) greater than 50%.

  10. Serum pregnancy test results of women of childbearing age should be negative within 7 days before the first administration of the test drug; Men who are fertile or women who are at risk of becoming pregnant must use a highly effective method of contraception (e.g., oral contraceptives, intrauterine devices, abstinence of sex or barrier contraception combined with spermicide) throughout the trial and continue to use contraception for 180 days after completion of treatment;
  11. Subjects voluntarily joined the study and signed informed consent with good compliance and follow-up.

Exclusion Criteria:

  1. Advanced treatment with CKIT inhibitors or PD-1/PD-L1 mab; Adjuvant therapy received CKIT inhibitor or PD-1/PD-L1 mab, and the drug withdrawal was less than 6 months;
  2. Associated with cerebral/meningeal metastasis;
  3. Patients who participated in or are participating in clinical trials of other drugs/therapies within 4 weeks prior to the first administration of the study drug;
  4. The study drug underwent/underwent major surgery or had not yet recovered from the side effects of the surgery, received live vaccination, immunotherapy, and received radiotherapy within 2 weeks before the first administration of the study drug;
  5. The patient has any active autoimmune disease or a history of autoimmune disease (such as, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism); Vitiligo that does not require systemic treatment may be included; Asthma with complete remission in childhood and without any intervention in adulthood could be included; Patients with asthma requiring medical intervention with bronchodilators were excluded);
  6. The patient is on immunosuppressant, or systemic hormone therapy for immunosuppression purposes (dose > 10mg/ day of prednisone or other equivalent hormone) and continued to use within 2 weeks prior to enrollment;
  7. A history of malignancies other than melanoma in the past 5 years, with the exception of cured basal cell carcinoma of the skin, squamous cell carcinoma of the skin, early-stage prostate cancer and carcinoma in situ of the cervix;
  8. Patients who had received hematopoietic stimulating factors, such as granulocyte colony stimulating factor (G-CSF) and erythropoietin, within 1 week before the first drug administration;
  9. Positive HIV antibody or treponema pallidum antibody;
  10. Patients with active hepatitis B or C:

    If HBsAg or HBcAb is positive, add test for HBV DNA(test result is higher than the upper limit of the normal range).

    If HCV antibody test result is positive, add test HCV RNA(test result is higher than normal value fan circumference upper limit);

  11. Known to be allergic to recombinant humanized PD-1 monoclonal antibody drugs and their components; Known to be allergic to imatinib mesylate and any excipients;
  12. Large pleural effusion, ascites and pericardial effusion accompanied by clinical symptoms and requiring symptomatic treatment;
  13. History of active pulmonary disease (interstitial pneumonia, pneumonia, obstructive pulmonary disease, asthma) or active pulmonary tuberculosis;
  14. Have any clinical problems beyond control, including but not limited to:

    Either a persistent or active (severe) infection; Hypoglycemic medication for poorly controlled hypertension (persistent blood pressure greater than 150/90 MMHG) Buying something to control diabetes poorly; Buying a ticket for heart disease (class III/IV congestive heart failure or heart block, as defined by the New York Cardiology Society); Anyway, something happened during the first six months before taking the drug: deep vein thrombosis or pulmonary embolism; myocardial infarction; severe or unstable arrhythmia or angina pectoris; percutaneous coronary intervention, acute coronary syndrome, coronary artery bypass grafting; Cerebrovascular accident, transient ischemic attack, cerebral embolism;

  15. Any conditions of the patient that affect the ingestion of the drug by the subject, and any conditions that affect the in-body disposal of the drug (absorption, distribution, metabolism or excretion);
  16. Abnormal coagulation (INR> 2.0, PT> 16s), have bleeding tendency or are receiving thrombolytic or anticoagulant therapy, and are allowed to use low-dose aspirin and low-molecular weight heparin prophylacically;
  17. The group of the first 3 months there have been significant clinical significance of bleeding symptoms or have a definite bleeding tendency, such as daily cough/haemoptysis 2.5 ml and above, gastrointestinal bleeding, there is a risk of bleeding of esophageal gastric varices, hemorrhagic peptic ulcers, or patients with vasculitis, baseline period if defecate occult blood positive, to review, after review if still positive, the need for gastroscopy, If severe esophagogastric fundus varices were indicated by gastroscopy, they could not be enrolled in the group (except those who were excluded by gastroscopy within 3 months before enrollment).
  18. Known hereditary or acquired bleeding and thrombotic tendencies (e.g., hemophiliacs, coagulopathy, thrombocytopenia, etc.);
  19. Have undergone a stem cell or organ transplant;
  20. Those who have a history of psychotropic drug abuse and cannot get rid of it or have a history of mental disorders;
  21. The investigator identifies other severe, acute, or chronic medical conditions or laboratory abnormalities that may increase the risk associated with study participation or may interfere with the interpretation of study results;

Sites / Locations

  • Beijing Cancer HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

JS001+Imatinib Mesylate

Arm Description

Imatinib: 400mg qd po. Toripalimab: 240mg q3w ivgtt. The longest cumulative use period of the two drugs was 2 years.

Outcomes

Primary Outcome Measures

Progression-free survival (PFS)
To evaluate progression-free survival (PFS) based on RECIST 1.1 criteria.

Secondary Outcome Measures

Overall response rate (ORR)
To evaluate the overall response rate (ORR) based on RECIST 1.1 criteria.
Disease control rate (DCR)
To evaluate the disease control rate (DCR) based on RECIST 1.1 criteria.
Overall survival (OS)
To evaluate overall survival (OS) based on RECIST 1.1 criteria.
Safety(AE,SAE)
To evaluate safety(AE,SAE) of imatinib mesylate combined with terriprizumab in patients with stage III unresectable and stage IV melanoma with CKIT gene mutation.

Full Information

First Posted
March 2, 2022
Last Updated
March 2, 2022
Sponsor
Peking University Cancer Hospital & Institute
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1. Study Identification

Unique Protocol Identification Number
NCT05274438
Brief Title
Imatinib and Toripalimab in Patients With Locally Advanced/Metastatic Melanoma Harbored With CKIT Mut
Official Title
A Single-arm, Phase II Clinical Study of Imatinib Mesylate Combined With Toripalimab in the Treatment of Stage III Unresectable and Stage IV Melanoma Harbored With CKIT Mut
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 26, 2021 (Actual)
Primary Completion Date
March 1, 2023 (Anticipated)
Study Completion Date
April 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Peking University Cancer Hospital & Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
It is a single-center, single-arm Phase II clinical study. This clinical trial aimed to evaluate the PFS of imatinib combined with toripalimab in stage III unresectable and stage IV melanoma with CKIT gene mutation.
Detailed Description
This study consisted of two phases: the first phase was the dose exploration phase, and the second phase was the extension group. In phase I, 3 patients were enrolled, starting with imatinib monotherapy, 400mg qd, for 2 cycles (6 weeks), followed by imatinib 400mg qd combined with toripalimab 240mg q3w. If DLT was not observed, the original dose was extended to 37 patients in phase ii; If there was 1 DLT in the first stage, the number of patients in the first stage was extended to 6. If there was no DLT, the patients entered the extended stage. If ≥2 DLT cases occurred in the first phase, imatinib was reduced to 300mg QD and toripalimab 240mg q3W, and the "3+3" study was restarted. If DLT≤1 case, enter extended group (imatinib 300mg qd and toripalimab 240mg q3W); The longest cumulative use period of the two drugs was 2 years. When patients develop disease progression or develop intolerable toxicity, treatment is ended and follow-up for survival is entered.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
37 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
JS001+Imatinib Mesylate
Arm Type
Experimental
Arm Description
Imatinib: 400mg qd po. Toripalimab: 240mg q3w ivgtt. The longest cumulative use period of the two drugs was 2 years.
Intervention Type
Drug
Intervention Name(s)
JS001+Imatinib mesylate
Intervention Description
This study consisted of two phases: the first phase was the dose exploration phase, and the second phase was the extension group. In phase I, 3 patients were enrolled, starting with imatinib monotherapy, 400mg qd, for 2 cycles (6 weeks), followed by imatinib 400mg qd combined with toripalimab 240mg q3w. If DLT was not observed, the original dose was extended to 37 patients in phase ii; If there was 1 DLT in the first stage, the number of patients in the first stage was extended to 6. If there was no DLT, the patients entered the extended stage. If ≥2 DLT cases occurred in the first phase, imatinib was reduced to 300mg QD and toripalimab 240mg q3W, and the "3+3" study was restarted. If DLT≤1 case, enter extended group (imatinib 300mg qd and toripalimab 240mg q3W); The longest cumulative use period of the two drugs was 2 years. When patients develop disease progression or develop intolerable toxicity, treatment is ended and follow-up for survival is entered.
Primary Outcome Measure Information:
Title
Progression-free survival (PFS)
Description
To evaluate progression-free survival (PFS) based on RECIST 1.1 criteria.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Overall response rate (ORR)
Description
To evaluate the overall response rate (ORR) based on RECIST 1.1 criteria.
Time Frame
2 years
Title
Disease control rate (DCR)
Description
To evaluate the disease control rate (DCR) based on RECIST 1.1 criteria.
Time Frame
2 years
Title
Overall survival (OS)
Description
To evaluate overall survival (OS) based on RECIST 1.1 criteria.
Time Frame
2 years
Title
Safety(AE,SAE)
Description
To evaluate safety(AE,SAE) of imatinib mesylate combined with terriprizumab in patients with stage III unresectable and stage IV melanoma with CKIT gene mutation.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥18, no gender limitation; Patients with recurrent, unresectable or metastatic melanoma confirmed by histopathology after surgery (stage III/IV); With CKIT gene mutation; Did not receive CKIT inhibitor or PD-1/PD-L1 mab treatment in late stage; Adjuvant therapy Patients who have received CKIT inhibitors or PD-1/PD-L1 mab should be discontinued for at least 6 months; ECOG score is 0 or 1; Expected survival ≥3 months; The investigator assessed the presence of at least one measurable lesion that had not been irradiated according to RECIST 1.1; No history of brain/meningeal metastasis; The organ function level must meet the following requirements (7 days before the first administration of the study drug): Spinal cord: Neutrophil absolute count (ANC)≥1.5×109/L, platelet (PLT)≥ 100×109/L, and hemoglobin (HB)≥9g/dL(no blood transfusion or component blood was received within 14 days prior to test); Gallo liver: Serum total bilirubin (TBIL)≤1.5 times the upper limit of normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT)≤2.5 times the upper limit of normal ( allows AST and ALT≤5 times the upper limit of normal if liver metastasis is present); serum creatinine ≤1.5 times the upper limit of normal value and endogenous creatinine clearance ≥50mL/min (Cockcroft-Gault formula); Accidence International standardized ratio (INR), activated partial thrombin time (aPTT)≤1.5 times the upper limit of normal value (only for patients not receiving anticoagulant therapy; Patients receiving anticoagulant therapy should keep the anticoagulant within the therapeutic range); Thyroid stimulating hormone (TSH)≤1×ULN (if abnormal, FT3 and FT4 levels should be investigated simultaneously; if FT3 and FT4 levels are normal, they can be included in the group) Isogenic urinary protein ≤1+, isogenic urinary protein & GT; 1+, urine protein should be collected for 24 hours, and the total amount should be less than or equal to 1 g; Unconsciously the heart functions normally, meaning normal or abnormal ECG has no clinical significance, while cardiac ultrasound shows left ventricular ejection fraction (LVEF) greater than 50%. Serum pregnancy test results of women of childbearing age should be negative within 7 days before the first administration of the test drug; Men who are fertile or women who are at risk of becoming pregnant must use a highly effective method of contraception (e.g., oral contraceptives, intrauterine devices, abstinence of sex or barrier contraception combined with spermicide) throughout the trial and continue to use contraception for 180 days after completion of treatment; Subjects voluntarily joined the study and signed informed consent with good compliance and follow-up. Exclusion Criteria: Advanced treatment with CKIT inhibitors or PD-1/PD-L1 mab; Adjuvant therapy received CKIT inhibitor or PD-1/PD-L1 mab, and the drug withdrawal was less than 6 months; Associated with cerebral/meningeal metastasis; Patients who participated in or are participating in clinical trials of other drugs/therapies within 4 weeks prior to the first administration of the study drug; The study drug underwent/underwent major surgery or had not yet recovered from the side effects of the surgery, received live vaccination, immunotherapy, and received radiotherapy within 2 weeks before the first administration of the study drug; The patient has any active autoimmune disease or a history of autoimmune disease (such as, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism); Vitiligo that does not require systemic treatment may be included; Asthma with complete remission in childhood and without any intervention in adulthood could be included; Patients with asthma requiring medical intervention with bronchodilators were excluded); The patient is on immunosuppressant, or systemic hormone therapy for immunosuppression purposes (dose > 10mg/ day of prednisone or other equivalent hormone) and continued to use within 2 weeks prior to enrollment; A history of malignancies other than melanoma in the past 5 years, with the exception of cured basal cell carcinoma of the skin, squamous cell carcinoma of the skin, early-stage prostate cancer and carcinoma in situ of the cervix; Patients who had received hematopoietic stimulating factors, such as granulocyte colony stimulating factor (G-CSF) and erythropoietin, within 1 week before the first drug administration; Positive HIV antibody or treponema pallidum antibody; Patients with active hepatitis B or C: If HBsAg or HBcAb is positive, add test for HBV DNA(test result is higher than the upper limit of the normal range). If HCV antibody test result is positive, add test HCV RNA(test result is higher than normal value fan circumference upper limit); Known to be allergic to recombinant humanized PD-1 monoclonal antibody drugs and their components; Known to be allergic to imatinib mesylate and any excipients; Large pleural effusion, ascites and pericardial effusion accompanied by clinical symptoms and requiring symptomatic treatment; History of active pulmonary disease (interstitial pneumonia, pneumonia, obstructive pulmonary disease, asthma) or active pulmonary tuberculosis; Have any clinical problems beyond control, including but not limited to: Either a persistent or active (severe) infection; Hypoglycemic medication for poorly controlled hypertension (persistent blood pressure greater than 150/90 MMHG) Buying something to control diabetes poorly; Buying a ticket for heart disease (class III/IV congestive heart failure or heart block, as defined by the New York Cardiology Society); Anyway, something happened during the first six months before taking the drug: deep vein thrombosis or pulmonary embolism; myocardial infarction; severe or unstable arrhythmia or angina pectoris; percutaneous coronary intervention, acute coronary syndrome, coronary artery bypass grafting; Cerebrovascular accident, transient ischemic attack, cerebral embolism; Any conditions of the patient that affect the ingestion of the drug by the subject, and any conditions that affect the in-body disposal of the drug (absorption, distribution, metabolism or excretion); Abnormal coagulation (INR> 2.0, PT> 16s), have bleeding tendency or are receiving thrombolytic or anticoagulant therapy, and are allowed to use low-dose aspirin and low-molecular weight heparin prophylacically; The group of the first 3 months there have been significant clinical significance of bleeding symptoms or have a definite bleeding tendency, such as daily cough/haemoptysis 2.5 ml and above, gastrointestinal bleeding, there is a risk of bleeding of esophageal gastric varices, hemorrhagic peptic ulcers, or patients with vasculitis, baseline period if defecate occult blood positive, to review, after review if still positive, the need for gastroscopy, If severe esophagogastric fundus varices were indicated by gastroscopy, they could not be enrolled in the group (except those who were excluded by gastroscopy within 3 months before enrollment). Known hereditary or acquired bleeding and thrombotic tendencies (e.g., hemophiliacs, coagulopathy, thrombocytopenia, etc.); Have undergone a stem cell or organ transplant; Those who have a history of psychotropic drug abuse and cannot get rid of it or have a history of mental disorders; The investigator identifies other severe, acute, or chronic medical conditions or laboratory abnormalities that may increase the risk associated with study participation or may interfere with the interpretation of study results;
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
lu Si, professor
Phone
13810700214
Email
silu15_silu@126.com
First Name & Middle Initial & Last Name or Official Title & Degree
Jun Guo, Diretcor
Phone
13911233048
Email
guoj307@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
jun Guo, Diretcor
Organizational Affiliation
Peking University Cancer Hospital & Institute
Official's Role
Study Chair
Facility Information:
Facility Name
Beijing Cancer Hospital
City
Beijing
State/Province
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jun Guo, Director
Phone
13911233048
Email
guoj307@126.com

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
21690468
Citation
Guo J, Si L, Kong Y, Flaherty KT, Xu X, Zhu Y, Corless CL, Li L, Li H, Sheng X, Cui C, Chi Z, Li S, Han M, Mao L, Lin X, Du N, Zhang X, Li J, Wang B, Qin S. Phase II, open-label, single-arm trial of imatinib mesylate in patients with metastatic melanoma harboring c-Kit mutation or amplification. J Clin Oncol. 2011 Jul 20;29(21):2904-9. doi: 10.1200/JCO.2010.33.9275. Epub 2011 Jun 20.
Results Reference
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Imatinib and Toripalimab in Patients With Locally Advanced/Metastatic Melanoma Harbored With CKIT Mut

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