Clinical trial NCT01933061: Study to Determine Efficacy and Safety of CC-486 With Nab-Paclitaxel Versus Nab-Paclitaxel in Patients With Chemotherapy naïve Metastatic Melanoma
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Metastatic Melanoma
Keywords: Skin cancer, Melanoma
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2013-08-30
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Up to 24 months
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: Up to 24 months
measure: PFS
timeFrame: Up to 24 months
measure: Objective Response Rate (ORR)
timeFrame: Up to 24 months
measure: Disease Control Rate (DCR)
timeFrame: Up to 24 months
measure: Safety
timeFrame: Up to 24 months
Other outcomes:
Locations:
Study officials:
affiliation: Celgene Corporation
name: Kirsten Hege, MD
role: STUDY_DIRECTOR
References: