Patient case: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

Clinical trial: Study to Determine Efficacy and Safety of CC-486 With Nab-Paclitaxel Versus Nab-Paclitaxel in Patients With Chemotherapy naïve 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.

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.

Eligibility: 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.

Relevance to patient case: not relevant