Phase I/II trial of nano-camptothecin CRLX101 with capecitabine and radiotherapy as neoadjuvant treatment for locally advanced rectal cancer

Hanna K. Sanoff, Dominic H. Moon, Dominic T. Moore, Jeremiah Boles, Courtney Bui, William Blackstock, Bert H. O'Neil, Somasundaram Subramaniam, Autumn J. McRee, Cheryl Carlson, Michael S. Lee, Joel E. Tepper, Andrew Z. Wang

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

CRLX101 is a nanoparticle-drug conjugate with a camptothecin payload. We assessed the toxicity and pathologic complete response (pCR) rate of CRLX101 with standard neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer. A single-arm study was conducted with a 3 + 3 dose escalation phase Ib followed by phase II at the maximum tolerated dose (MTD). Thirty-two patients were enrolled with 29 (91%) patients having T3/4 and 26 (81%) N1/2 disease. In phase Ib, no patient experienced a dose limiting toxicity (DLT) with every other week dosing, while 1/9 patients experienced a DLT with weekly dosing. The weekly MTD was identified as 15 mg/m 2 . The most common grade 3–4 toxicity was lymphopenia, with only 1 grade 4 event. pCR was achieved in 6/32 (19%) patients overall and 2/6 (33%) patients at the weekly MTD. CRLX101 at 15 mg/m 2 weekly with neoadjuvant CRT is a feasible combination strategy with an excellent toxicity profile. Clinicaltrials.gov registration NCT02010567

Original languageEnglish (US)
Pages (from-to)189-195
Number of pages7
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume18
DOIs
StatePublished - Jun 2019
Externally publishedYes

Keywords

  • Camptothecin
  • Maximum tolerated dose
  • Nanoparticle
  • Neoadjuvant
  • Pathologic complete response
  • Rectal cancer

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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  • Cite this

    Sanoff, H. K., Moon, D. H., Moore, D. T., Boles, J., Bui, C., Blackstock, W., O'Neil, B. H., Subramaniam, S., McRee, A. J., Carlson, C., Lee, M. S., Tepper, J. E., & Wang, A. Z. (2019). Phase I/II trial of nano-camptothecin CRLX101 with capecitabine and radiotherapy as neoadjuvant treatment for locally advanced rectal cancer. Nanomedicine: Nanotechnology, Biology, and Medicine, 18, 189-195. https://doi.org/10.1016/j.nano.2019.02.021