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

doi:10.1016/j.nano.2019.02.021

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 journal › Article › peer-review

22 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

Original language	English (US)
Pages (from-to)	189-195
Number of pages	7
Journal	Nanomedicine: Nanotechnology, Biology, and Medicine
Volume	18
DOIs	https://doi.org/10.1016/j.nano.2019.02.021
State	Published - Jun 2019
Externally published	Yes

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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10.1016/j.nano.2019.02.021

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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

Sanoff, HK, Moon, DH, Moore, DT, Boles, J, Bui, C, Blackstock, W, O'Neil, BH, Subramaniam, S, McRee, AJ, Carlson, C, Lee, MS, Tepper, JE & Wang, AZ 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, vol. 18, pp. 189-195. https://doi.org/10.1016/j.nano.2019.02.021

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

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",

keywords = "Camptothecin, Maximum tolerated dose, Nanoparticle, Neoadjuvant, Pathologic complete response, Rectal cancer",

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

note = "Funding Information: This research was supported by Cerulean Pharma Inc. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",

year = "2019",

month = jun,

doi = "10.1016/j.nano.2019.02.021",

language = "English (US)",

volume = "18",

pages = "189--195",

journal = "Nanomedicine: Nanotechnology, Biology, and Medicine",

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T1 - Phase I/II trial of nano-camptothecin CRLX101 with capecitabine and radiotherapy as neoadjuvant treatment for locally advanced rectal cancer

AU - Sanoff, Hanna K.

AU - Moon, Dominic H.

AU - Moore, Dominic T.

AU - Boles, Jeremiah

AU - Bui, Courtney

AU - Blackstock, William

AU - O'Neil, Bert H.

AU - Subramaniam, Somasundaram

AU - McRee, Autumn J.

AU - Carlson, Cheryl

AU - Lee, Michael S.

AU - Tepper, Joel E.

AU - Wang, Andrew Z.

PY - 2019/6

Y1 - 2019/6

N2 - 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

AB - 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

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KW - Maximum tolerated dose

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KW - Neoadjuvant

KW - Pathologic complete response

KW - Rectal cancer

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

Abstract

Keywords

ASJC Scopus subject areas

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