study to determine efficacy and safety of cc-486 with nab-paclitaxel versus nab-paclitaxel in patients with chemotherapy naïve metastatic melanoma

Conditions: Metastatic Melanoma

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.

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.

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.

Keywords: skin cancer, melanoma