Bevacizumab Combined With Carboplatin Plus Paclitaxel Chemotherapy to Treat Metastatic Mucosal Melanoma

Study Overview
=================
Brief Summary
-----------------
Mucosal melanoma is rare and associated with extremely poor prognosis.No effective treatment for advanced mucosal melanoma patients.Investigators conducted a randomized phase II study in patients with previously untreated metastatic mucosal melanoma to characterize the efficacy and safety of bevacizumab when combined with carboplatin plus paclitaxel.

Detailed Description
-----------------
Mucosal melanoma is rare and associated with extremely poor prognosis.It is the second most common subtype in Asians.No effective treatment for advanced mucosal melanoma patients.Malignant melanoma is a highly vascular tumor in which vascular endothelial growth factor(VEGF) is strongly expressed and seems to play an important role in disease progression.A randomized phase II study evaluated the activity of Bevacizumab in combination with carboplatin plus paclitaxel(CPB arm) in patients with previously untreated advanced melanoma.Overall response rates was 25.5%,median overall survival time(OS) was 12.3 months in the CPB arm. Investigators conducted a randomized phase II study in patients with previously untreated metastatic mucosal melanoma to characterize the efficacy and safety of bevacizumab when combined with carboplatin plus paclitaxel.

Official Title
-----------------
A Randomized Phase II Study Evaluating the Activity of Bevacizumab in Combination With Carboplatin Plus Paclitaxel in Patients With Previously Untreated Advanced Mucosal Melanoma

Conditions
-----------------
Melanoma

Intervention / Treatment
-----------------
* Drug: Paclitaxel
* Drug: Carboplatin
* Drug: Bevacizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed mucosal melanoma with metastases and has no received any systemic treatment. ECOG performance status 0, 1 Estimated life expectancy of 12 weeks or greater Age 18 years or older, male or female At least one measurable site (diameter≥1cm) of disease (RECIST 1.1). Adequate organ function Without symptoms of brain metastases and stable in neuro-functions. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures Exclusion Criteria: Mutations in C-KIT or BRAF-V600E, asked for other target treatments Pregnant or lactation women Acute infections without control. Heart disease history, cardiac function class≥NYHA II. HIV positive or chronic HBV/HCV in active stage. Brain metastases or primary tumor with positive symptoms Need anti-epileptic treatments Organ transplantation history Hemorrhagic tendency or related history Renal dialysis patients Diagnosis of any second malignancy within the last 3 years, except for adequately treated. Current treatment on another clinical trial The other improper situations which investigator judged.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BEV plus Chemotherapy<br>Paclitaxel 175mg/m2, d1; Carboplatin AUC=5, d1; Bevacizumab 5mg/kg, d1、15; 28 days a cycle | Drug: Paclitaxel<br>* 175 mg/m^2 by IV infusion on the first day of each 4-week cycle (dose was based on patient's weight and could be adjusted for weight change)<br>* Other names: Taxel;Drug: Carboplatin<br>* Dose based on patients' creatinine clearance (Calvert formula) and administered by intravenous (IV) infusion on the first day of each 4-week cycle<br>* Other names: CBP;Drug: Bevacizumab<br>* 5mg/kg by intravenous (IV) infusion every two weeks of each 4-week cycle (dose was based on patient's weight at screening and remained the same throughout study)<br>* Other names: BEV;|
| Active Comparator: Chemotherapy alone<br>Paclitaxel 175mg/m2, d1; Carboplatin AUC=5, d1; 28 days a cycle | Drug: Paclitaxel<br>* 175 mg/m^2 by IV infusion on the first day of each 4-week cycle (dose was based on patient's weight and could be adjusted for weight change)<br>* Other names: Taxel;Drug: Carboplatin<br>* Dose based on patients' creatinine clearance (Calvert formula) and administered by intravenous (IV) infusion on the first day of each 4-week cycle<br>* Other names: CBP;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progress-free survival(PFS) | Progression Free Survival is defined as the time from enrollment to the date of first documented disease progression or death from any cause. | From randomization up to 144 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adverse event(AE) | Any events,no matter related to interventions,occur during the period from the enrollment to death or 30 days after withdrawal from the trial | From randomization up to144 weeks | 
| Overall Survival(OS) | Overall survival was defined as the time from randomization to death from any cause. | Up to 144 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Carboplatin, mucosal melanoma, Bevacizumab, Paclitaxel