Phase II Study in the Treatment of Patients With Advanced Mucinous Melanoma

NCT03941795 | Unknown Phase 2

• 1 other identifier: BJCH-MM-0624
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 2

Brief Summary

This is a randomized, controlled, multicenter Phase II clinical study to evaluate the efficacy and safety of toripalimab injection combined with axitinib in the first-line treatment of patients with advanced mucosal melanoma. The target population is the patients with previously untreated, histopathologically confirmed, unresectable or metastatic mucosal melanoma. At the randomization, patients are randomized 1:1:1 into three groups with approximately 33 subjects in each group to receive toripalimab injection plus axitinib, toripalimab injection monotherapy (subjects who meet the criteria after disease progression may cross over to receive toripalimab plus axitinib), or axitinib monotherapy (subjects who meet the criteria after disease progression may cross over to receive toripalimab plus axitinib); when the patient has disease progression or intolerable toxicity, the treatment is terminated, and the survival follow-up will be initiated.

Conditions

Advanced Mucosal Melanoma

Keywords

PD-1 monoclonal antibody; the First Line Therapy; Axitinib; Mucosal Melanoma; Toripalimab; JS001

Outcome Measures

Primary Outcomes (1)

• the progression-free survival (PFS)

  Progression-free survival (PFS) per RECIST 1.1 criteria: Time from the date of randomization to the first documented disease progression (per RECIST 1.1 criteria), or death from any cause, whichever occurs first.

  36 months

Secondary Outcomes (8)

• INV-ORR

  36 months

• ORR

  36 months

• PFS

  36 months

• DOR

  36 months

• TTR

  36 months

Study Arms (3)

JS001(Toripalimab Injection) Combined With Axitinib

EXPERIMENTAL

Other: JS001 and Axitinib

JS001 alone

EXPERIMENTAL

Biological: JS001(Toripalimab Injection)

Axitinib alone

ACTIVE COMPARATOR

Drug: Axitinib 1 MG [Inlyta]

Interventions

JS001(Toripalimab Injection) BIOLOGICAL

Test Group: Toripalimab (240 mg, IV, Q3W) + axitinib (5 mg/tablet, one tablet, twice a day, orally); axitinib is started on the second day of administration of toripalimab until disease progression or intolerable toxicity, the investigator or subject decides to withdraw, lost to follow-up, initiation of other antineoplastic therapy, or death, with a maximum duration of toripalimab use of no more than 2 years.

JS001 alone

Axitinib 1 MG [Inlyta] DRUG

Axitinib (5 mg/tablet) one tablet, twice a day, orally until disease progression or intolerable toxicity, the investigator or subject decides to withdraw, lost to follow-up, initiation of other antineoplastic therapy, or death

Axitinib alone

JS001 and Axitinib OTHER

Control Group: Toripalimab (240 mg, IV, Q3W) is administered on the first day until disease progression or intolerable toxicity, the investigator or subject decides to withdraw, lost to follow-up, initiation of other antineoplastic therapy, or death, with a maximum duration of no more than 2 years

JS001(Toripalimab Injection) Combined With Axitinib

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women, aged 18 to 80 years.
• Patients with pathohistologically confirmed, unresectable or metastatic mucosal melanoma.
• No prior treatment with any systemic antineoplastic agents (prior adjuvant or neoadjuvant therapy is allowed, but should be completed at least 3 weeks prior to randomization and all related adverse events have returned to normal or CTC-AE Grade 1).
• Have a score of 0 or 1 on the ECOG scale.
• Tumor tissue samples must be available for PD-L1 expression testing.
• At least one measurable lesion according to RECIST 1.1, and the lesion has not been irradiated.
• Organ function must meet the following requirements (within 7 days prior to randomization):
• Peripheral blood: absolute neutrophil count (ANC) ≥1.5 × 109/L, platelets (PLT) ≥100 × 109/L, hemoglobin (HB) ≥9 g/dL (no blood transfusion or blood components within 14 days before testing); Liver: Serum bilirubin (TBIL) ≤1.5 x upper limit of normal (ULN),, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 x ULN (≤5 x ULN in case of liver metastases); Serum creatinine ≤1.5 x ULN; International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤1.5 x ULN (only for patients not receiving anticoagulant therapy; patients receiving anticoagulant therapy should keep the anticoagulant within the therapeutic requirements); Normal cardiac function, i.e., normal or abnormal electrocardiogram without clinical significance, and left ventricular ejection fraction (LVEF) greater than 50% on cardiac ultrasound.
• Women of childbearing age must have a negative pregnancy test within 7 days prior to treatment; men of reproductive potential or women of childbearing potential must use highly effective contraceptive methods (e.g., oral contraceptives, intrauterine contraceptive devices, abstinence or barrier contraception in combination with spermicides) throughout the trial and continue contraception for 3 months after the end of treatment.
• Subjects are willing to participate in this study and sign informed consent form, have good compliance and cooperate with the follow-up.

You may not qualify if:

• Patients previously treated with anti-PD-1, anti-PD-L1, anti-PD-L2 therapy and/or VEGFR TKIs.
• Patients who have participated in or are participating in clinical trial of other drug/therapy within 4 weeks prior to this study treatment (before randomization).
• Major surgery, live vaccination, immunotherapy within 4 weeks prior to study start, and radiotherapy within 2 weeks prior to study start.
• History of malignancy other than mucosal melanoma within the past 3 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 received hematopoietic stimulating factors, such as granulocyte colony-stimulating factor (G-CSF) and erythropoietin, within 1 week prior to study start.
• HIV test positive.
• Patients with active hepatitis B or C:
• If HBsAg or HBcAb is positive, additionally test HBV DNA (results above the lower limit of detection at site);
• If the result of HCV antibody test is positive, additionally test HCV RNA.
• Known to be allergic to recombinant humanized PD-1 monoclonal antibody drug and its components; known to be allergic to axitinib and any of its excipients.
• Hypertension that cannot be controlled by medication.
• Massive pleural effusion or ascites with clinical symptoms requiring symptomatic management.
• Subjects with active central nervous system (CNS) metastases are excluded. Subjects with metastatic brain lesions are eligible if they have received treatment and have no evidence of disease progression on magnetic resonance imaging (MRI) at least 8 weeks after completion of treatment and within 28 days before the first dose. Immunosuppressive doses of systemic corticosteroids (\>10 mg/day prednisone equivalent) must not be required at least 2 weeks prior to study drug administration.
• History of active pulmonary tuberculosis.
• Have any uncontrollable clinical problems, including but not limited to:

Sponsors & Collaborators

• Peking University Cancer Hospital & Institute: lead

Study Sites (2)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

RECRUITING

Baishen First Hospital of Jilin University

Shengyang, Liaoning, China

NOT YET RECRUITING

MeSH Terms

Interventions

Axitinib

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Jun Guo, MD,PhD

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jun Guo, MD,PhD

CONTACT

010-88121122; Guoj307@126.com

Xinan Sheng, MD

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of department of renal cancer and melanoma

Study Record Dates

• First Submitted: May 5, 2019
• First Posted: May 8, 2019
• Study Start: November 11, 2019
• Primary Completion: June 1, 2022
• Study Completion: December 1, 2022
• Last Updated: December 6, 2019

Record last verified: 2019-12

Locations

CN (2)