GEICO1601-ROLANDO: a multicentric single arm Phase II clinical trial to evaluate the combination of olaparib and pegylated liposomal doxorubicin for platinum-resistant ovarian cancer

J Alejandro Perez-Fidalgo, Maria Iglesias, Uriel Bohn, Elisa Calvo, Yolanda Garcia, Eva Guerra, Luis Manso, Ana Santaballa, Antonio Gonzalez-Martin, J Alejandro Perez-Fidalgo, Maria Iglesias, Uriel Bohn, Elisa Calvo, Yolanda Garcia, Eva Guerra, Luis Manso, Ana Santaballa, Antonio Gonzalez-Martin

Abstract

Response to polyadenosine diphosphate ribose polymerase (PARP) inhibitors in platinum-resistant ovarian cancer and in the absence of BRCA mutations is very low. Combining PARP inhibitors with other agents might overcome this lack of activity. Here we describe the rationale and design of GEICO1601-ROLANDO (resistant ovarian cancer treated with olaparib and pegylated liposomal doxorubin; NCT03161132). ROLANDO is a Phase II single-arm multicenter trial in which patients are treated with a combination of olaparib and pegylated liposomal doxorubicin (PLD) in platinum-resistant epithelial ovarian, primary peritoneal, or Fallopian tube cancer regardless of the BRCA mutation status. The primary end point is progression-free survival at 6 months. Other secondary end points are response rate, disease control rate, quality of life and overall survival.

Keywords: maintenance; olaparib; ovarian cancer; pegylated liposomal doxorubicin; platinum-resistant.

Conflict of interest statement

Financial & competing interests disclosure This trial received financial support from AstraZeneca. JA Perez-Fidalgo discloses lectures, advisories or traveling support from AstraZeneca, Roche, Pharmamar, Clovis and Pfizer. E Guerra discloses a role as advisory board for AstraZeneca. L Manso discloses lectures, advisories/consultant role and research funding from Tesaro, AstraZeneca, Roche, Novartis and Celgene. A Gonzalez-Martin discloses lectures, advisories or traveling support from AstraZeneca, Roche, Tesaro, Clovis, Pfizer-Merck and Pharmamar. The rest of the authors have no disclosures to declare. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Figures

Figure 1. . Treatment schedule of the…
Figure 1.. Treatment schedule of the GEICO1601-ROLANDO trial.
b.i.d.: Twice daily.

References

    1. Jayson GC, Kohn E, Kitchener HC, Ledermann JA. Ovarian cancer. Lancet. 2014;384(9951):1376–1388.
    1. Reid BM, Permuth JB, Seller TA. Epidemiology of ovarian cancer: a review. Cancer Biol. Med. 2017;14(1):9–32.
    1. Colombo PE, Fabbro M, Theillet C, Bibeau F, Rouanet P, Ray-Coquard I. Sensitivity and resistance to treatment in the primary management of epithelial ovarian cancer. Crit. Rev. Oncol. Hematol. 2014;89(2):207–216.
    1. Desai A, Xu J, Aysola K, et al. Epithelial ovarian cancer: an overview. World J. Transl. Med. 2014;3(1):1–8.
    1. Markman M, Bookman MA. Second-line treatment of ovarian cancer. Oncologist. 2000;5(1):25–35.
    1. Fong PC, Boss DS, Yap TA, et al. Inhibition of poly (ADP-ribose) polymerase in tumors from BRCA-carriers. N. Eng. J. Med. 2009;361:123–134.
    1. Fong PC, Yap TA, Boss DS, et al. Poly (ADP-ribose) polymerase inhibition: frequent durable responses in BRCA carrier ovarian cancer correlating with platinum-free interval. J. Clin. Oncol. 2010;28:2512–2519.
    1. Audeh MH, Carmichael J, Penson RT, et al. Oral poly-ADP ribose polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations in recurrent ovarian cancer: a proof-of-concept trial. Lancet Oncol. 2010;376:245–251.
    1. Kaufman B, Shapira-Frommer R, Schmutzler RK, et al. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J. Clin. Oncol. 2015;33(3):244–250.
    1. Gelmon KA, Tischkowitz M, Mackay H, et al. Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a Phase II, multicentre, open-label, non-randomised study. Lancet Oncol. 2011;12(9):852–861.
    1. Kaye SB, Lubinsky J, Matulonis U, et al. Phase II open-label, randomized multicenter study comparing the efficacy and safety of olaparib, a poly (ADP-ribose) polymerase inhibitor and pegylated liposomal doxorubicin in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer. J. Clin. Oncol. 2011;30:372–379.
    1. Oza AM, Cibula D, Oaknin A, et al. Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: a randomized Phase II trial. Lancet Oncol. 2015;16:87–97.
    1. Del Conte G, Sessa C, Von Moos R, et al. Phase I study of olaparib in combination with liposomoal doxorubicin in patients with advanced solid tumors. B. J. Cancer. 2014;111:651–659.
    1. Eetezadi S, Evans JC, Shen Y-T, De Souza R, Piquette-Miller M, Allen C. Ratio-dependent synergism of doxorubicin and olaparib combination in 2D and spheroid models of ovarian cancer. Mol. Pharm. 2018;15:472–485.

Source: PubMed

Sponsorzy i współpracownicy

Warunki medyczne

Interwencje lekowe

3
Subskrybuj