Metastatic Melanoma
Conditions
Keywords
Skin cancer, Melanoma
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.
Interventions
DRUGAbraxane
Abraxane 150- mg/m² IV on Days 1, 8, and 15 of a 28-day cycle
Sponsors
Celgene Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | Up to 24 months | PFS is defined as the time from randomization date to disease progression according to RECIST response guideline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | Up to 24 months | OS is defined as the time from the date of randomization to the date of death. |
| PFS | Up to 24 months | PFS based on investigator assessment; PFS is defined as the time from randomization date to disease progression according to RECIST response guideline |
| Objective Response Rate (ORR) | Up to 24 months | Number (%) of subject who achieve an objective complete or partial response. |
| Disease Control Rate (DCR) | Up to 24 months | Number (%) of subject with Stable Disease (SD) ≥ for 18 weeks or complete or partial response. |
| Safety | Up to 24 months | 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. |
Outcome results
None listed