A Study of Toripalimab or Combining With Temozolomide（iv） in the Treatment of Advanced/Metastatic Malignant Melanoma

Sponsor

First Affiliated Hospital of Zhejiang University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04884997

Collaborator

(none)

Enrollment

Location

Arms

42.1

Anticipated Duration (Months)

2.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study evaluate toripalimab or combining with temozolomide for injection in the treatment of advanced/metastatic malignant melanoma. Participants in arm A receive toripalimab, in arm B receive toripalimab plus temozolomide

Condition or Disease	Intervention/Treatment	Phase
Malignant Melanoma	Drug: toripalimab Drug: Temozolomide Injection	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Exploratory Study of PD-1 Antibody(Toripalimab) or Combining With Temozolomide for Injection in the Treatment of Advanced/Metastatic Malignant Melanoma

Actual Study Start Date :

Mar 7, 2021

Anticipated Primary Completion Date :

Mar 7, 2024

Anticipated Study Completion Date :

Sep 7, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm A toripalimab 3mg/kg, Q2w;	Drug: toripalimab toripalimab 3mg/kg, Q2w; Other Names: triprizumab
Experimental: Arm B toripalimab 3mg/kg, Q2w; Temozolomide 150mg/m2,d1-5,Q4w	Drug: toripalimab toripalimab 3mg/kg, Q2w; Other Names: triprizumab Drug: Temozolomide Injection Temozolomide 150mg/m2,d1-5,Q4w Other Names: Temoda

Arm

Intervention/Treatment

Active Comparator: Arm A

toripalimab 3mg/kg, Q2w;

Drug: toripalimab

toripalimab 3mg/kg, Q2w;

Other Names:

triprizumab

Experimental: Arm B

toripalimab 3mg/kg, Q2w; Temozolomide 150mg/m2,d1-5,Q4w

Drug: toripalimab

toripalimab 3mg/kg, Q2w;

Other Names:

triprizumab

Drug: Temozolomide Injection

Temozolomide 150mg/m2,d1-5,Q4w

Other Names:

Temoda

Outcome Measures

Primary Outcome Measures

ORR [8 weeks]
objective response rate

Secondary Outcome Measures

OS [3 years]
overall survival
PFS [1 years]
Progression free survival
DCR [8 weeks]
Disease contral rate
1-year PFS [1 year after treatment initiation]
progression free survival at 1 year (1year PFS) rate
6-month PFS [6 months after treatment initiation]
progression free survival at 6 months (6-month PFS) rate
1-year OS [1 year after treatment initiation]
overall survival at 1 year (1 year OS) rate
2-year OS [2 year after treatment initiation]
overall survival at 2 years (2 year OS) rate

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

•Confirmed pathologic or cytologic diagnosis of advanced/metastatic malignant melanomawithout BRAF V600E mutation
ECOG PS 0-1;
Age :18 ~75 years old;
There were measurable lesions according to RECIST 1.1 and the lesions that had been irradiated showed definite progression after radiotherapy and the lesion was considered measurable only if it was not the only lesion
Proper function of the cardiovascular system, liver, kidney and bone marrow ;
Subject with at most one systemic therapy for advanced/metastatic malignant melanoma
Survival is expected to exceed 3 months
The subjects showing good compliance voluntarily participated in the study and signed the informed consent

Exclusion Criteria:

•Previously treated with TMZ, PD-1, or PD-L1;
Complicated with other malignant tumors;
Subjects with central nervous system metastases and/or cancerous meningitis;(Unless the subjects are asymptomatic or have been treated , no radiographic evidence of new BMs or BMs enlargement is found at least 2 weeks after BMs treatment.If the subjects have active or new untreated asymptomatic central nervous system (CNS) metastases found on imaging during the screening phase,they must receive radiotherapy
Uncontrolled pleural effusion ,pericardial effusion or ascites requiring repeated drainage
Received major surgical treatment or significant traumatic injury within Random 28 days prior
Severe arterial/venous thrombosis events，Such as cerebrovascular accident (including temporary ischemic attack) ,deep vein thrombosis and pulmonary embolismwithin Random 6 months prior
Subjects with a history of psychotropic substance abuse and being unable to get rid of it or with mental disorders
Subjects with any severe and/or uncontrolled disease,including :

Subjects with poor blood pressure control (systolic≥ 150 mmHg or diastolic ≤100mmHg)
Subjects with myocardial ischemia or myocardial infarction or arrhythmia above grade I (including male QTC ≥450ms(male) and female QTC ≥470ms) And ≥grade 2 congestive heart failure (New York Heart Association (NYHA))
Active or uncontrolled severe infection (≥CTC AE grade 2 infection)
liver cirrhosis,active hepatitis*;*active hepatitis(Hepatitis B reference: HBsAg positive, and HBV DNA test value exceeds the normal valueHepatitis C reference: HCV antibody positive, and HCV virus titer detection value exceeds the upper limit of normal value
HIV infected
Poor diabetes control (fasting blood glucose (FBG) > 10mmol/L)
urine protein≥++,andConfirmated 24-hour urinary protein quantification>1.0 g
Subjects received a preventive vaccineor attenuated vaccine within 4 weeks
prior to first administration
Participated in other clinical trials within 4 weeks
Active autoimmune disease（Such as the following, but not limited to: autoimmune hepatitis interstitial pneumonia enteritis vasculitis, nephritis。Subjects with asthma requiring bronchodilators for medical intervention were not included） requiring systemic treatment（Such as the use of palliative drugs, corticosteroids, or immunosuppressants） occurred within 2 years prior to initial administration.Alternative therapy(Examples include thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) is not considered systemic therapy
Other conditions that investigators consider the patients are not suitable