Dose-finding Study of CAELYXTM and RAD001 in Patients With Advanced Solid Tumors

Summary

This is a dose finding, open-label, uncontrolled, dose-escalation trial to determine the Maximum Tolerated Dose (MTD) and the Recommended Dose (RD) of the combination RAD001 (escalating daily dose) and CaelyxTM (fixed dose) to patients with advanced solid tumors. Other purposes of the study are: 1. define the safety profile of the combination after repeated administrations 2. define hints of antitumor activity, to be confirmed in subsequent disease-oriented expansion phases at the RD. 3. define the pharmacokinetic profile of the combination

Timeline

Start

2007-10

Primary completion

2011-03

Completion

2011-12

Publications

• Background Guba M, von Breitenbuch P, Steinbauer M, Koehl G, Flegel S, Hornung M, Bruns CJ, Zuelke C, Farkas S, Anthuber M, Jauch KW, Geissler EK. Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor. Nat Med. 2002 Feb;8(2):128-35. doi: 10.1038/nm0202-128.
• Background Pollock Rea: Cell shrinkage, cell cycle arrest and anti-angiogenesis underlie the anti-tumor activity of the m-TOR inhibitor AP23573, AACR-NCI-EORTC International Conference, 2003, pp Abstr. B160
• Background Tan C, Cruet-Hennequart S, Troussard A, Fazli L, Costello P, Sutton K, Wheeler J, Gleave M, Sanghera J, Dedhar S. Regulation of tumor angiogenesis by integrin-linked kinase (ILK). Cancer Cell. 2004 Jan;5(1):79-90. doi: 10.1016/s1535-6108(03)00281-2.
• Background Brown NS, Bicknell R. Thymidine phosphorylase, 2-deoxy-D-ribose and angiogenesis. Biochem J. 1998 Aug 15;334 ( Pt 1)(Pt 1):1-8. doi: 10.1042/bj3340001.
• Background Parmar MK, Ledermann JA, Colombo N, du Bois A, Delaloye JF, Kristensen GB, Wheeler S, Swart AM, Qian W, Torri V, Floriani I, Jayson G, Lamont A, Trope C; ICON and AGO Collaborators. Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet. 2003 Jun 21;361(9375):2099-106. doi: 10.1016/s0140-6736(03)13718-x.
• Background Stewart, C. F. and Ratain, M. J. Topoisomerase interactive agents. In: V. T. DeVita, Jr., S. Hellman, and S. A. Rosenberg (eds.), Cancer: Principles and practice of oncology, pp. 452-467. Philadelphia: Lippincott-Raven Publishers, 1997.
• Background Riggs, C. E. J. Antitumor antibiotics and related compounds. In: M. C. Perry (ed.) The chemotherapy source book, 2nd edition, pp. 345-386. Baltimore: Williams and Wilkins, 1997.
• Background Lyass O, Uziely B, Ben-Yosef R, Tzemach D, Heshing NI, Lotem M, Brufman G, Gabizon A. Correlation of toxicity with pharmacokinetics of pegylated liposomal doxorubicin (Doxil) in metastatic breast carcinoma. Cancer. 2000 Sep 1;89(5):1037-47. doi: 10.1002/1097-0142(20000901)89:53.0.co;2-z.
• Background Ranson MR, Carmichael J, O'Byrne K, Stewart S, Smith D, Howell A. Treatment of advanced breast cancer with sterically stabilized liposomal doxorubicin: results of a multicenter phase II trial. J Clin Oncol. 1997 Oct;15(10):3185-91. doi: 10.1200/JCO.1997.15.10.3185.

Drugs

Indications