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Phase III Trial to Evaluate the Efficacy and Safety of JS001 Combined With Axitinib for Advanced Mucosal Melanoma

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ClinicalTrials.gov Identifier: NCT03941795
Recruitment Status : Recruiting
First Posted : May 8, 2019
Last Update Posted : May 8, 2019
Sponsor:
Information provided by (Responsible Party):
Jun Guo, Beijing Cancer Hospital

Tracking Information
First Submitted Date  ICMJE May 5, 2019
First Posted Date  ICMJE May 8, 2019
Last Update Posted Date May 8, 2019
Estimated Study Start Date  ICMJE May 2019
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 6, 2019)
the progression-free survival (PFS) [ Time Frame: 2 years ]
To compare Toripalimab Injection in combination with Axitinib versus Toripalimab Injection alone with regard to independent review committee (IRC) assessed progression-free survival (PFS) in previously untreated, unresectable (stage III) or metastatic (stage IV) mucosal melanoma patients.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: May 6, 2019)
  • the progression-free survival (PFS) [ Time Frame: 2 years ]
    Progression-free survival (PFS) evaluated by the investigator based on RECIST1.1 criteria
  • Objective response rate (ORR) [ Time Frame: 2 years ]
    Objective response rate (ORR) between two treatment groups evaluated by the independent review committee (IRC) on radiological data in accordance with RECIST 1.1 criteria
  • duration of response (DOR) [ Time Frame: 2 years ]
    Duration of response (DOR) between two treatment groups evaluated by the independent review committee (IRC) on radiological data in accordance with RECIST 1.1 criteria
  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 2 years ]
    To evaluate the overall safety of Toripalimab Injection alone or in combination with Axitinib
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase III Trial to Evaluate the Efficacy and Safety of JS001 Combined With Axitinib for Advanced Mucosal Melanoma
Official Title  ICMJE Effect and Safety Profile of Axitinib Combination With JS001 Injection for Advanced Mucosal Melanoma: a Prospective Phase III, Randomized Controlled Trial
Brief Summary This is a randomized, controlled, multi-center phase III clinical study to evaluate the efficacy and safety of JS001(Toripalimab Injection) combined with Axitinib as first-line therapy in patients with advanced mucosal melanoma. The target population are treatment-naive patients with histopathologically confirmed, unresectable stage III or stage IV mucosal melanoma. At randomization, the patients will be 1:1 randomized to two groups (73 subjects in each): the test group will receive Toripalimab Injection combined with Axitinib; the control group will receive Toripalimab Injection alone; when disease progression or intolerable toxicity occurs in a group, the treatment will be ended in that group while survival follow-up starts.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Melanoma
Intervention  ICMJE
  • Biological: JS001(Toripalimab Injection)
    recombinant humanized anti-PD-1 monoclonal antibody injection (JS001)
  • Drug: Axitinib
    Axitinib is an oral, potent, multitarget tyrosine kinase receptor inhibitor.
Study Arms  ICMJE
  • Experimental: JS001(Toripalimab Injection) Combined With Axitinib
    Toripalimab (240 mg, IV, Q3W) + Axitinib (5 mg/tablet, 1 tablet once, BID, continuous oral administration)
    Interventions:
    • Biological: JS001(Toripalimab Injection)
    • Drug: Axitinib
  • Active Comparator: JS001(Toripalimab Injection) alone
    Toripalimab(240 mg, IV, Q3W)
    Intervention: Biological: JS001(Toripalimab Injection)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 6, 2019)
146
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 1. Age of 18-75 years, male or female.
  • 2. Patients with unresectable stage III or metastatic stage IV mucosal melanoma as confirmed by the histopathological examination.
  • 3. Not previously treated with any systemic anti-tumor drug (allowable for adjuvant treatment or new adjuvant treatment completed at least 3 weeks before randomization, and all relevant adverse events have been restored to normal level or the Grade I defined by CTC -AE 4.03.
  • 4. ECOG score 0 or 1.
  • 5. must provide tumor tissue specimen for PD-L1 expression test.
  • 6. With at least one measurable lesion as per RECIST 1.1 criteria, which has not been irradiated.
  • 7. The organ function level must meet the following requirements (7 days prior to randomization):

    1. Peripheral blood: absolute neutrophil count (ANC)≥1.5×109/L, platelet count (PLT)≥100×109/L and hemoglobin (HB) ≥9 g/dL (no blood or blood component transfusion within 14 days prior to testing);
    2. Liver: serum bilirubin total (TBIL) ≤1.5 × ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT)≤3 × ULN (or AST, ALT ≤5 × ULN in case of liver metastasis);
    3. Serum creatinine ≤ 1.5 × ULN or endogenous creatinine clearance ≥ 50 mL/min (using Cockcroft-Gault formula);
    4. International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤1.5 × ULN (only applicable for the patients not receiving an anticoagulant therapy and those receiving anticoagulant therapy should make the anticoagulants meet treatment requirements);
    5. Normal cardiac function, i.e. normal result or abnormal result of no clinical significance at ECG examination, left ventricular ejection fraction (LVEF) >50% at the cardiac ultrasound.
  • 8. Women of childbearing age have to have negative pregnancy test within 7d before treatment; men of reproduction ability or women of pregnant possibility must adopt the highly-effective contraceptive methods during the whole study (e.g. oral contraceptives, intrauterine contraceptive device, abstinence of sexual intercourse or barrier contraception in combination with spermatocide), and continue contraception for 3 months after the end of treatment.
  • 9. Being voluntary to participate in the study, sign the informed consent form, with good compliance and willingness to cooperate with follow-up.

Exclusion Criteria:

  • 1. Patients who were previously treated with anti-PD-1, anti-PD-L1, anti-PD-L2 and/or VEGFR TKI.
  • 2. Patients who has participated or is participating the clinical studies with other drug or therapy within 4 weeks prior to enrollment in the study ( before randomization).
  • 3. Patients who received major surgical operation, live vaccine and immunotherapy within 4 weeks before initiation of the study; and radiotherapy within 2 weeks.
  • 4. Malignant tumors other than mucosal melanoma within the recent 3 years, except the cured skin basal cell carcinoma, skin squamous cell carcinoma, early prostate cancer and cervical carcinoma in situ.
  • 5. Receiving the hematopoietic stimulating factors (e.g. granulocyte colony-stimulating factor (G-CSF) and erythropoietin) within 1 week before initiation of the study.
  • 6. Positive test for HIV;
  • 7. Patients with active hepatitis B or C:

    1. In case of positive HBsAg or HBcAb, perform additional HBV DNA test (the result is higher than lower limit of detection specified by the study site).
    2. In case of positive HCV antibody test, perform additional HCV RNA test .
  • 8. Known allergy to recombinant humanized PD-1 monoclonal antibody drug and its components; known allergy to Axitinib and any of its excipients.
  • 9. Uncontrolled hypertension on drugs.
  • 10.Massive hydrothorax or ascites with clinical symptoms and requiring the symptomatic treatment.
  • 11.Subjects with active central nervous system (CNS) metastasis will be excluded. Active cerebral or leptomeningeal metastases. Subjects with brain metastases are eligible if they have received treatment and there is no evidence of disease progression in nuclear magnetic resonance imaging (MRI) for at least 8 weeks after the completion of treatment and within 28 days prior to the first dose. Meanwhile, it is mandatory that systemic corticosteroids at immunosuppressive doses (>10 mg/day of prednisone equivalent) are not needed for at least 2 weeks prior to administration of the study drugs.
  • 12.With medical history of active tuberculosis.
  • 13. With any uncontrollable clinical problem, including but not limited to:

    1. Suffering from autoimmune disease, or with a history of autoimmune disease or with a history of syndrome requiring the systemic treatment with steroid/immunosuppressants, e.g. hypophysitis, pneumonia, colonitis, hepatitis, nephritis, hyperthyroidism and hypothyroidism;
    2. The following conditions occur within 6 months prior to randomization: 1) deep vein thrombosis or pulmonary embolism; 2) percutaneous coronary intervention, acute coronary syndrome, coronary artery bypass grafting; 3) cerebrovascular accident, transient ischemic attack.
    3. Other serious, uncontrolled concomitant diseases that may affect compliance with the protocol or interfere with the interpretation of the results, including active opportunistic infection or progressive (serious) infection, uncontrolled diabetes, cardiovascular disease (grade Ⅲ or Ⅳ heart failure defined in accordance with New York Heart Association grading system, >grade Ⅱ cardiac conduction block, myocardial infarction, unstable arrhythmia or unstable angina pectoris in the past 6 months, cerebral infarction in the past three months, etc.) or pulmonary disease (interstitial pneumonia, obstructive pulmonary disease and history of symptomatic bronchospasm);
  • 14. Patients with any conditions influencing the swallowing of drugs, and any condition influencing the in vivo absorption or PK of investigational product , including the gastrointestinal excision or surgery of any type.
  • 15. Previous stem cell transplant or organ transplant.
  • 16. Women of childbearing potential or pregnant or lactating women with positive serum or urine pregnancy test within 7 days prior to start of treatment.
  • 17. Previous addiction to anti-psychotics unable to abstain, or with a history of mental disorder.
  • 18. Other severe, acute or chronic medical diseases or abnormalities in laboratory examination possibly increasing the relevant risk in study participation or possibly interfering the interpretation of study results as judged by the investigator.
  • 19. Poor compliance or other conditions inapplicable for study participation as judged by the investigator.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jun Guo, MD,PhD 010-88121122 Guoj307@126.com
Contact: Xinan Sheng, MD
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03941795
Other Study ID Numbers  ICMJE BJCH-MM-0624
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jun Guo, Beijing Cancer Hospital
Study Sponsor  ICMJE Beijing Cancer Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jun Guo, MD,PhD Beijing Cancer Hospital
PRS Account Beijing Cancer Hospital
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP