Phase Ib/II study of elisidepsin in metastatic or advanced gastroesophageal cancer (IMAGE trial)

Russell Petty, Alan Anthoney, Jean-Philippe Metges, Maria Alsina, Anthony Gonçalves, Jennifer R. Brown, Clara Montagut, Katharina Gunzer, Gianluca Laus, Jorge Luis Iglesias Dios, Bernardo Miguel-Lillo, Patrick Bohan, Ramón Salazar (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    9 Citations (Scopus)

    Abstract

    Purpose: To determine the recommended dose and antitumor activity of single-agent elisidepsin as a 24-h intravenous (i.v.) infusion fortnightly [biweekly, d1 and 15 every 4 weeks (q4wk); Arm A, dose-intensity strategy] or as a 3-h i.v. infusion weekly (d1, 8, 15 and 22 q4wk; Arm B, dose-density strategy) in adult patients with unresectable, locally advanced or metastatic pretreated esophageal, gastroesophageal junction and gastric cancer.

    Methods: Patients were randomized to one of two elisidepsin dosing schedules. Phase Ib starting doses were 8.0 mg flat dose (FD) in Arm A and 3.0 mg FD in Arm B. Phase II subsequently explored antitumor activity of both dosing schedules at the respective recommended doses.

    Results: Forty-four patients received elisidepsin: 12 in stage Ib and 32 in stage II. The recommended doses were defined as 10 mg FD (Arm A) and 3.75 mg FD (Arm B). Both schedules were well tolerated. Most adverse events were mild or moderate, reversible and predictable with no meaningful differences between schedules. The pharmacokinetic profiles of both schedules were similar to those reported previously in patients with solid tumors treated with a comparable dose. An interim analysis found tumor control in one patient receiving elisidepsin fortnightly, and in none given elisidepsin weekly; patient accrual was therefore discontinued due to lack of efficacy.

    Conclusions: Both schedules at the recommended doses presented an acceptable safety profile, but lack of response means that we do not recommend further evaluation of single-agent elisidepsin as chemotherapy for unresectable, locally advanced or metastatic gastroesophageal cancer.

    Original languageEnglish
    Pages (from-to)819-27
    Number of pages9
    JournalCancer Chemotherapy and Pharmacology
    Volume77
    Issue number4
    Early online date10 Mar 2016
    DOIs
    Publication statusPublished - Apr 2016

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    Appointments and Schedules
    Neoplasms
    Intravenous Infusions
    Tumors
    Esophagogastric Junction
    Pharmacokinetics
    Chemotherapy
    Stomach Neoplasms
    elisidepsin
    Safety
    Drug Therapy

    Keywords

    • Elisidepsin
    • PM02734
    • Esophageal cancer
    • Esophagogastric junction cancer
    • Gastric cancer
    • Gastroesophageal cancer

    Cite this

    Petty, Russell ; Anthoney, Alan ; Metges, Jean-Philippe ; Alsina, Maria ; Gonçalves, Anthony ; Brown, Jennifer R. ; Montagut, Clara ; Gunzer, Katharina ; Laus, Gianluca ; Iglesias Dios, Jorge Luis ; Miguel-Lillo, Bernardo ; Bohan, Patrick ; Salazar, Ramón. / Phase Ib/II study of elisidepsin in metastatic or advanced gastroesophageal cancer (IMAGE trial). In: Cancer Chemotherapy and Pharmacology. 2016 ; Vol. 77, No. 4. pp. 819-27.
    @article{162e34e9f8a5468b86d4cb7087ab00d6,
    title = "Phase Ib/II study of elisidepsin in metastatic or advanced gastroesophageal cancer (IMAGE trial)",
    abstract = "Purpose: To determine the recommended dose and antitumor activity of single-agent elisidepsin as a 24-h intravenous (i.v.) infusion fortnightly [biweekly, d1 and 15 every 4 weeks (q4wk); Arm A, dose-intensity strategy] or as a 3-h i.v. infusion weekly (d1, 8, 15 and 22 q4wk; Arm B, dose-density strategy) in adult patients with unresectable, locally advanced or metastatic pretreated esophageal, gastroesophageal junction and gastric cancer.Methods: Patients were randomized to one of two elisidepsin dosing schedules. Phase Ib starting doses were 8.0 mg flat dose (FD) in Arm A and 3.0 mg FD in Arm B. Phase II subsequently explored antitumor activity of both dosing schedules at the respective recommended doses.Results: Forty-four patients received elisidepsin: 12 in stage Ib and 32 in stage II. The recommended doses were defined as 10 mg FD (Arm A) and 3.75 mg FD (Arm B). Both schedules were well tolerated. Most adverse events were mild or moderate, reversible and predictable with no meaningful differences between schedules. The pharmacokinetic profiles of both schedules were similar to those reported previously in patients with solid tumors treated with a comparable dose. An interim analysis found tumor control in one patient receiving elisidepsin fortnightly, and in none given elisidepsin weekly; patient accrual was therefore discontinued due to lack of efficacy.Conclusions: Both schedules at the recommended doses presented an acceptable safety profile, but lack of response means that we do not recommend further evaluation of single-agent elisidepsin as chemotherapy for unresectable, locally advanced or metastatic gastroesophageal cancer.",
    keywords = "Elisidepsin, PM02734, Esophageal cancer, Esophagogastric junction cancer, Gastric cancer, Gastroesophageal cancer",
    author = "Russell Petty and Alan Anthoney and Jean-Philippe Metges and Maria Alsina and Anthony Gon{\cc}alves and Brown, {Jennifer R.} and Clara Montagut and Katharina Gunzer and Gianluca Laus and {Iglesias Dios}, {Jorge Luis} and Bernardo Miguel-Lillo and Patrick Bohan and Ram{\'o}n Salazar",
    note = "{\circledC} Springer-Verlag Berlin Heidelberg 2016",
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    Petty, R, Anthoney, A, Metges, J-P, Alsina, M, Gonçalves, A, Brown, JR, Montagut, C, Gunzer, K, Laus, G, Iglesias Dios, JL, Miguel-Lillo, B, Bohan, P & Salazar, R 2016, 'Phase Ib/II study of elisidepsin in metastatic or advanced gastroesophageal cancer (IMAGE trial)', Cancer Chemotherapy and Pharmacology, vol. 77, no. 4, pp. 819-27. https://doi.org/10.1007/s00280-016-2991-0

    Phase Ib/II study of elisidepsin in metastatic or advanced gastroesophageal cancer (IMAGE trial). / Petty, Russell; Anthoney, Alan; Metges, Jean-Philippe; Alsina, Maria; Gonçalves, Anthony; Brown, Jennifer R.; Montagut, Clara; Gunzer, Katharina; Laus, Gianluca; Iglesias Dios, Jorge Luis; Miguel-Lillo, Bernardo; Bohan, Patrick; Salazar, Ramón (Lead / Corresponding author).

    In: Cancer Chemotherapy and Pharmacology, Vol. 77, No. 4, 04.2016, p. 819-27.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Phase Ib/II study of elisidepsin in metastatic or advanced gastroesophageal cancer (IMAGE trial)

    AU - Petty, Russell

    AU - Anthoney, Alan

    AU - Metges, Jean-Philippe

    AU - Alsina, Maria

    AU - Gonçalves, Anthony

    AU - Brown, Jennifer R.

    AU - Montagut, Clara

    AU - Gunzer, Katharina

    AU - Laus, Gianluca

    AU - Iglesias Dios, Jorge Luis

    AU - Miguel-Lillo, Bernardo

    AU - Bohan, Patrick

    AU - Salazar, Ramón

    N1 - © Springer-Verlag Berlin Heidelberg 2016

    PY - 2016/4

    Y1 - 2016/4

    N2 - Purpose: To determine the recommended dose and antitumor activity of single-agent elisidepsin as a 24-h intravenous (i.v.) infusion fortnightly [biweekly, d1 and 15 every 4 weeks (q4wk); Arm A, dose-intensity strategy] or as a 3-h i.v. infusion weekly (d1, 8, 15 and 22 q4wk; Arm B, dose-density strategy) in adult patients with unresectable, locally advanced or metastatic pretreated esophageal, gastroesophageal junction and gastric cancer.Methods: Patients were randomized to one of two elisidepsin dosing schedules. Phase Ib starting doses were 8.0 mg flat dose (FD) in Arm A and 3.0 mg FD in Arm B. Phase II subsequently explored antitumor activity of both dosing schedules at the respective recommended doses.Results: Forty-four patients received elisidepsin: 12 in stage Ib and 32 in stage II. The recommended doses were defined as 10 mg FD (Arm A) and 3.75 mg FD (Arm B). Both schedules were well tolerated. Most adverse events were mild or moderate, reversible and predictable with no meaningful differences between schedules. The pharmacokinetic profiles of both schedules were similar to those reported previously in patients with solid tumors treated with a comparable dose. An interim analysis found tumor control in one patient receiving elisidepsin fortnightly, and in none given elisidepsin weekly; patient accrual was therefore discontinued due to lack of efficacy.Conclusions: Both schedules at the recommended doses presented an acceptable safety profile, but lack of response means that we do not recommend further evaluation of single-agent elisidepsin as chemotherapy for unresectable, locally advanced or metastatic gastroesophageal cancer.

    AB - Purpose: To determine the recommended dose and antitumor activity of single-agent elisidepsin as a 24-h intravenous (i.v.) infusion fortnightly [biweekly, d1 and 15 every 4 weeks (q4wk); Arm A, dose-intensity strategy] or as a 3-h i.v. infusion weekly (d1, 8, 15 and 22 q4wk; Arm B, dose-density strategy) in adult patients with unresectable, locally advanced or metastatic pretreated esophageal, gastroesophageal junction and gastric cancer.Methods: Patients were randomized to one of two elisidepsin dosing schedules. Phase Ib starting doses were 8.0 mg flat dose (FD) in Arm A and 3.0 mg FD in Arm B. Phase II subsequently explored antitumor activity of both dosing schedules at the respective recommended doses.Results: Forty-four patients received elisidepsin: 12 in stage Ib and 32 in stage II. The recommended doses were defined as 10 mg FD (Arm A) and 3.75 mg FD (Arm B). Both schedules were well tolerated. Most adverse events were mild or moderate, reversible and predictable with no meaningful differences between schedules. The pharmacokinetic profiles of both schedules were similar to those reported previously in patients with solid tumors treated with a comparable dose. An interim analysis found tumor control in one patient receiving elisidepsin fortnightly, and in none given elisidepsin weekly; patient accrual was therefore discontinued due to lack of efficacy.Conclusions: Both schedules at the recommended doses presented an acceptable safety profile, but lack of response means that we do not recommend further evaluation of single-agent elisidepsin as chemotherapy for unresectable, locally advanced or metastatic gastroesophageal cancer.

    KW - Elisidepsin

    KW - PM02734

    KW - Esophageal cancer

    KW - Esophagogastric junction cancer

    KW - Gastric cancer

    KW - Gastroesophageal cancer

    U2 - 10.1007/s00280-016-2991-0

    DO - 10.1007/s00280-016-2991-0

    M3 - Article

    VL - 77

    SP - 819

    EP - 827

    JO - Cancer Chemotherapy and Pharmacology

    JF - Cancer Chemotherapy and Pharmacology

    SN - 0344-5704

    IS - 4

    ER -