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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Metastatic Melanoma
• Intervention / Treatment: Drug: Abraxane; Drug: Abraxane

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.

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Abraxane 150 mg/m² Intravenous (IV)	Drug: Abraxane; Abraxane 150- mg/m² IV on Days 1, 8, and 15 of a 28-day cycle; Other Names: nab-paclitaxel, ABI-007; Drug: Abraxane; Abraxane 150 mg/m^2 intravenously on Days 1, 8, and 15 of a 28-day cycle; Other Names: nab-paclitaxel, ABI-007
EXPERIMENTAL: CC-486 orally plus Abraxane IV	Drug: Abraxane; Abraxane 150- mg/m² IV on Days 1, 8, and 15 of a 28-day cycle; Other Names: nab-paclitaxel, ABI-007; Drug: Abraxane; Abraxane 150 mg/m^2 intravenously on Days 1, 8, and 15 of a 28-day cycle; 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

Collaborators and Investigators

• Sponsor: Celgene Corporation
• Investigators: Study Director: Kirsten Hege, MD, Celgene Corporation

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (ACTUAL): January 1, 2014
• Study Completion (ACTUAL): January 1, 2014

Study Registration Dates

• First Submitted: August 28, 2013
• First Submitted That Met QC Criteria: August 28, 2013
• First Posted (ESTIMATE): August 30, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): February 4, 2014
• Last Update Submitted That Met QC Criteria: February 3, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: Skin cancer, Melanoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Albumin-Bound Paclitaxel
• Other Study ID Numbers: CC-486-MEL-001