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

Nanomedicine. 2019 Jun;18:189-195. doi: 10.1016/j.nano.2019.02.021. Epub 2019 Mar 8.


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/m2. 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/m2 weekly with neoadjuvant CRT is a feasible combination strategy with an excellent toxicity profile. registration NCT02010567.

Keywords: Camptothecin; Maximum tolerated dose; Nanoparticle; Neoadjuvant; Pathologic complete response; Rectal cancer.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / adverse effects
  • Camptothecin / therapeutic use*
  • Capecitabine / adverse effects
  • Capecitabine / therapeutic use*
  • Cohort Studies
  • Cyclodextrins / adverse effects
  • Cyclodextrins / therapeutic use*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nanoparticles / chemistry*
  • Neoadjuvant Therapy*
  • Neoplasm Staging
  • Rectal Neoplasms / drug therapy*
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / radiotherapy*


  • Cyclodextrins
  • IT-101
  • Capecitabine
  • Camptothecin

Associated data