Phase I study to determine the safety, tolerability and immunostimulatory activity of thalidomide analogue CC-5013 in patients with metastatic malignant melanoma and other advanced cancers

J B Bartlett, A Michael, I A Clarke, K Dredge, S Nicholson, H Kristeleit, A Polychronis, H Pandha, G W Muller, D I Stirling, J Zeldis, A G Dalgleish

    Research output: Contribution to journalArticle

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    Abstract

    We assessed the safety, tolerability and efficacy of the immunomodulatory drug, CC-5013 (REVIMID trade mark ), in the treatment of patients with metastatic malignant melanoma and other advanced cancers. A total of 20 heavily pretreated patients received a dose-escalating regimen of oral CC-5013. Maximal tolerated dose, toxicity and clinical responses were evaluated and analysis of peripheral T-cell surface markers and serum for cytokines and proangiogenic factors were performed. CC-5013 was well tolerated. In all, 87% of adverse effects were classified as grade 1 or grade 2 according to Common Toxicity Criteria and there were no serious adverse events attributable to CC-5013 treatment. Six patients failed to complete the study, three because of disease progression, two withdrew consent and one was entered inappropriately and withdrawn from the study. The remaining 14 patients completed treatment without dose reduction, with one patient achieving partial remission. Evidence of T-cell activation was indicated by significantly increased serum levels of sIL-2 receptor, granulocyte-macrophage colony-stimulating factor, interleukin-12 (IL-12), tumour necrosis factor-alpha and IL-8 in nine patients from whom serum was available. However, levels of proangiogenic factors vascular endothelial growth factor and basic foetal growth factor were not consistently affected. This study demonstrates the safety, tolerability and suggests the clinical activity of CC-5013 in the treatment of refractory malignant melanoma. Furthermore, this is the first report demonstrating T-cell stimulatory activity of this class of compound in patients with advanced cancer.
    Original languageEnglish
    Pages (from-to)955-61
    Number of pages7
    JournalBritish Journal of Cancer
    Volume90
    Issue number5
    DOIs
    Publication statusPublished - 2004

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    Thalidomide
    Melanoma
    Safety
    Neoplasms
    T-Lymphocytes
    Granulocyte-Macrophage Colony-Stimulating Factor Receptors
    Maximum Tolerated Dose
    Therapeutics
    Interleukin-12
    Fetal Development
    lenalidomide
    Serum
    Interleukin-8
    Vascular Endothelial Growth Factor A
    Disease Progression
    Intercellular Signaling Peptides and Proteins
    Tumor Necrosis Factor-alpha
    Biomarkers
    Cytokines
    Pharmaceutical Preparations

    Cite this

    Phase I study to determine the safety, tolerability and immunostimulatory activity of thalidomide analogue CC-5013 in patients with metastatic malignant melanoma and other advanced cancers. / Bartlett, J B; Michael, A; Clarke, I A; Dredge, K; Nicholson, S; Kristeleit, H; Polychronis, A; Pandha, H; Muller, G W; Stirling, D I; Zeldis, J; Dalgleish, A G.

    In: British Journal of Cancer, Vol. 90, No. 5, 2004, p. 955-61.

    Research output: Contribution to journalArticle

    Bartlett, JB, Michael, A, Clarke, IA, Dredge, K, Nicholson, S, Kristeleit, H, Polychronis, A, Pandha, H, Muller, GW, Stirling, DI, Zeldis, J & Dalgleish, AG 2004, 'Phase I study to determine the safety, tolerability and immunostimulatory activity of thalidomide analogue CC-5013 in patients with metastatic malignant melanoma and other advanced cancers', British Journal of Cancer, vol. 90, no. 5, pp. 955-61. https://doi.org/10.1038/sj.bjc.6601579
    Bartlett, J B ; Michael, A ; Clarke, I A ; Dredge, K ; Nicholson, S ; Kristeleit, H ; Polychronis, A ; Pandha, H ; Muller, G W ; Stirling, D I ; Zeldis, J ; Dalgleish, A G. / Phase I study to determine the safety, tolerability and immunostimulatory activity of thalidomide analogue CC-5013 in patients with metastatic malignant melanoma and other advanced cancers. In: British Journal of Cancer. 2004 ; Vol. 90, No. 5. pp. 955-61.
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    AU - Dredge, K

    AU - Nicholson, S

    AU - Kristeleit, H

    AU - Polychronis, A

    AU - Pandha, H

    AU - Muller, G W

    AU - Stirling, D I

    AU - Zeldis, J

    AU - Dalgleish, A G

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