Study to Determine Efficacy and Safety of CC-486 With Nab-Paclitaxel Versus Nab-Paclitaxel in Patients With Chemotherapy naïve Metastatic Melanoma

Study Overview
=================
Brief Summary
-----------------
A phase 2, open-label randomized, multicenter trial to compare CC-486 in combination with Abraxane administered weekly with respect to overall survival, objective tumor response rate and Progression-Free Survival (PFS) in participants diagnosed with metastatic malignant melanoma.

Detailed Description
-----------------
The study will consist of the following phases: Screening (Baseline) Assessments: Performed within 21 days of randomization. Randomization: Subjects will be randomized within 21 days of starting their Baseline assessments. Treatment: Therapy may continue in the absence of clinically significant disease progression and unacceptable toxicity. Response Assessments: Subjects will be evaluated by investigators for CR, PR, stable or progressive disease every 6 weeks from the start of treatment until progressive disease is documented. Responders and subjects with stable disease (SD) should continue on study unless they develop unacceptable toxicity, they start a new anticancer therapy, withdrawal of consent, physician decision or death. End of Study (EOS)/Treatment Evaluation: At the time subjects are removed from study, laboratory and clinical evaluations will be performed. Follow-up for Disease Progression: - Subjects who stop treatment prior to developing disease progression should be followed without further treatment until progressive disease is documented or until the treating physician feels additional treatment is required. Follow-up for Survival: Post study, subject survival status will be monitored on a monthly basis for 6 months from discontinuation from the study and every 3 months thereafter, until death or study termination in all subjects.

Official Title
-----------------
A Randomized, Open Label, Multi-center Phase 2 Study of Nab-Paclitaxel Versus Epigenetic Modifying Therapy of CC-4386 With Nab-Paclitaxel in Subjects With Chemotherapy naïve Metastatic Melanoma

Conditions
-----------------
Metastatic Melanoma

Intervention / Treatment
-----------------
* Drug: Abraxane
* Drug: Abraxane


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. Histologically or cytologically confirmed cutaneous BRAF wild-type malignant melanoma with evidence of metastasis (Stage IV). 2. No prior cytotoxic chemotherapy for metastatic malignant melanoma is permitted. No prior adjuvant cytotoxic chemotherapy is permitted. Up to one prior regimen with the following classes of agents is permitted: o Targeted biologic agents (e.g. interleukin 2 [IL-2], granulocyte macrophage colony stimulating factor [GM-CSF], other cytokines or unarmed monoclonal antibodies) o Targeted small molecule inhibitors (e.g., kinase inhibitors, heat shock protein [HSP] inhibitors, etc.). Immune checkpoint inhibitors (e.g. anti-CTLA4, anti-PD1, anti-PD-L1). Prior adjuvant therapy with interferon and/or vaccines is permitted. Prior treatments should be completed 4 weeks prior to enrollment in the study (ie, randomization). 3. Male or non-pregnant and non-lactating female, and ≥ 18 years of age at the time of signing the informed consent document. If heterosexually active, the subject must agree to use medical doctor-approved contraception throughout the study, and for 6 months after last dose of study drug. 4. History of malignancy in the last 5 years; subjects with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. Subjects with other malignancies are eligible if they were cured by surgery (with or without radiotherapy) and have been continuously disease-free for at least 5 years. 5. Radiographically-documented measurable disease (defined by the presence of at least one radiographically documented measurable lesion including measurable cutaneous metastasis). 6. Adequate haemtological and biochemical parameters: ANC ≥ 1.5 x 109 cells/L. Platelets ≥ 100 x 109 cells/L. Hgb ≥ 9 g/dL. AST (SGOT) or ALT (SGPT) ≥ 2.5x upper limit of normal range (ULN); o ≤ 5.0 x ULN if hepatic metastases present. Total bilirubin ≤ ULN. Creatinine ≤ 1.5 mg/dL. 8. ECOG performance status 0 to 1. Exclusion Criteria: 1. History of or current evidence of symptomatic brain metastases (brain Computed Tomography (CT)/Magnetic Resonance Imaging (MRI) is needed to exclude brain metastasis), including leptomeningeal involvement. 2. Subject has pre-existing peripheral neuropathy of National Cancer Institute NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Scale of Grade ≥ 2. 3. Prior radiation to a target lesion is permitted only if there has been clear progression of the lesion since radiation was completed.

Ages Eligible for Study
-----------------
Minimum Age: 18 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: Abraxane 150 mg/m² Intravenous (IV)<br> | Drug: Abraxane<br>* Abraxane 150- mg/m² IV on Days 1, 8, and 15 of a 28-day cycle<br>* Other names: nab-paclitaxel, ABI-007;|
| Experimental: CC-486 orally plus Abraxane IV<br> | Drug: Abraxane<br>* Abraxane 150 mg/m^2 intravenously on Days 1, 8, and 15 of a 28-day cycle<br>* Other names: nab-paclitaxel, ABI-007;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | PFS is defined as the time from randomization date to disease progression according to RECIST response guideline | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | OS is defined as the time from the date of randomization to the date of death. | Up to 24 months | 
| PFS | PFS based on investigator assessment; PFS is defined as the time from randomization date to disease progression according to RECIST response guideline | Up to 24 months | 
| Objective Response Rate (ORR) | Number (%) of subject who achieve an objective complete or partial response. | Up to 24 months | 
| Disease Control Rate (DCR) | Number (%) of subject with Stable Disease (SD) ≥ for 18 weeks or complete or partial response. | Up to 24 months | 
| Safety | Incidence and severity of Adverse events (AE) will be analyzed in terms of treatment-emergent AEs defined to be any AE that begin or worsen in severity after study drug initiation. | Up to 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Skin cancer, Melanoma