Pilot trial of CRLX101 in patients with advanced, chemotherapyrefractory gastroesophageal cancer

Joseph Chao, James Lin, Paul Frankel, Andrew J. Clark, Devin T. Wiley, Edward Garmey, Marwan Fakih, Dean Lim, Vincent Chung, Eloise Luevanos, Scott Eliasof, Mark E. Davis, Yun Yen

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: CRLX101 is an investigational nanoparticle-drug conjugate with a camptothecin payload. Preclinical evidence indicated preferential uptake in tumors, and tumor xenograft models demonstrate superiority of CRLX101 over irinotecan. A pilot trial was conducted at recommended phase 2 dosing (RP2D) using the bimonthly schedule to assess preferential uptake of CRLX101 in tumor vs. adjacent normal tissue in endoscopically accessible tumors in chemotherapy-refractory gastroesophageal cancer. Results from the biopsies were previously reported and herein we present the clinical outcomes. Methods: Patients initiated CRLX101 dosed at RP2D (15 mg/m2) on days 1 and 15 of a 28-day cycle. Detection of preferential CRLX101 tumor uptake was the primary endpoint and objective response rate (ORR) was a secondary endpoint. With a sample size of ten patients, the study had 90% power to detect ≥1 responder if the true response rate is ≥21%. Results: Between Dec. 2012 and Dec. 2014, ten patients with chemotherapy-refractory (median 2 prior lines of therapy, range 1-4) gastric adenocarcinoma were enrolled. The median time-to-progression was 1.7 months. Best response was seen in one patient with stable disease (SD) for 8 cycles. Only ≥ grade 3 drugrelated toxicity occurred in one patient with grade 3 cardiac chest pain who was able to resume therapy after CRLX101 was reduced to 12 mg/m2. Conclusions: Bimonthly CRLX101 demonstrated minimal activity with SD as best response in this heavily pretreated population. Future efforts with CRLX101 in gastric cancer should focus on combination and more dose-intensive strategies given its favorable toxicity profile and evidence of preferential tumor uptake.

Original languageEnglish
Pages (from-to)962-969
Number of pages8
JournalJournal of Gastrointestinal Oncology
Volume8
Issue number6
DOIs
Publication statusPublished - Dec 1 2017

Fingerprint

Neoplasms
irinotecan
Investigational Drugs
Drug Therapy
Camptothecin
IT-101
Chest Pain
Heterografts
Sample Size
Nanoparticles
Stomach Neoplasms
Stomach
Appointments and Schedules
Adenocarcinoma
Biopsy
Therapeutics
Population

Keywords

  • Clinical trial
  • CRLX101
  • Esophageal cancer
  • Gastric cancer

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology

Cite this

Pilot trial of CRLX101 in patients with advanced, chemotherapyrefractory gastroesophageal cancer. / Chao, Joseph; Lin, James; Frankel, Paul; Clark, Andrew J.; Wiley, Devin T.; Garmey, Edward; Fakih, Marwan; Lim, Dean; Chung, Vincent; Luevanos, Eloise; Eliasof, Scott; Davis, Mark E.; Yen, Yun.

In: Journal of Gastrointestinal Oncology, Vol. 8, No. 6, 01.12.2017, p. 962-969.

Research output: Contribution to journalArticle

Chao, J, Lin, J, Frankel, P, Clark, AJ, Wiley, DT, Garmey, E, Fakih, M, Lim, D, Chung, V, Luevanos, E, Eliasof, S, Davis, ME & Yen, Y 2017, 'Pilot trial of CRLX101 in patients with advanced, chemotherapyrefractory gastroesophageal cancer', Journal of Gastrointestinal Oncology, vol. 8, no. 6, pp. 962-969. https://doi.org/10.21037/jgo.2017.08.10
Chao, Joseph ; Lin, James ; Frankel, Paul ; Clark, Andrew J. ; Wiley, Devin T. ; Garmey, Edward ; Fakih, Marwan ; Lim, Dean ; Chung, Vincent ; Luevanos, Eloise ; Eliasof, Scott ; Davis, Mark E. ; Yen, Yun. / Pilot trial of CRLX101 in patients with advanced, chemotherapyrefractory gastroesophageal cancer. In: Journal of Gastrointestinal Oncology. 2017 ; Vol. 8, No. 6. pp. 962-969.
@article{605af8330c2f4fbbb73bc1107167631b,
title = "Pilot trial of CRLX101 in patients with advanced, chemotherapyrefractory gastroesophageal cancer",
abstract = "Background: CRLX101 is an investigational nanoparticle-drug conjugate with a camptothecin payload. Preclinical evidence indicated preferential uptake in tumors, and tumor xenograft models demonstrate superiority of CRLX101 over irinotecan. A pilot trial was conducted at recommended phase 2 dosing (RP2D) using the bimonthly schedule to assess preferential uptake of CRLX101 in tumor vs. adjacent normal tissue in endoscopically accessible tumors in chemotherapy-refractory gastroesophageal cancer. Results from the biopsies were previously reported and herein we present the clinical outcomes. Methods: Patients initiated CRLX101 dosed at RP2D (15 mg/m2) on days 1 and 15 of a 28-day cycle. Detection of preferential CRLX101 tumor uptake was the primary endpoint and objective response rate (ORR) was a secondary endpoint. With a sample size of ten patients, the study had 90{\%} power to detect ≥1 responder if the true response rate is ≥21{\%}. Results: Between Dec. 2012 and Dec. 2014, ten patients with chemotherapy-refractory (median 2 prior lines of therapy, range 1-4) gastric adenocarcinoma were enrolled. The median time-to-progression was 1.7 months. Best response was seen in one patient with stable disease (SD) for 8 cycles. Only ≥ grade 3 drugrelated toxicity occurred in one patient with grade 3 cardiac chest pain who was able to resume therapy after CRLX101 was reduced to 12 mg/m2. Conclusions: Bimonthly CRLX101 demonstrated minimal activity with SD as best response in this heavily pretreated population. Future efforts with CRLX101 in gastric cancer should focus on combination and more dose-intensive strategies given its favorable toxicity profile and evidence of preferential tumor uptake.",
keywords = "Clinical trial, CRLX101, Esophageal cancer, Gastric cancer",
author = "Joseph Chao and James Lin and Paul Frankel and Clark, {Andrew J.} and Wiley, {Devin T.} and Edward Garmey and Marwan Fakih and Dean Lim and Vincent Chung and Eloise Luevanos and Scott Eliasof and Davis, {Mark E.} and Yun Yen",
year = "2017",
month = "12",
day = "1",
doi = "10.21037/jgo.2017.08.10",
language = "English",
volume = "8",
pages = "962--969",
journal = "Journal of Gastrointestinal Oncology",
issn = "2078-6891",
publisher = "Pioneer Bioscience Publishing Company (PBPC)",
number = "6",

}

TY - JOUR

T1 - Pilot trial of CRLX101 in patients with advanced, chemotherapyrefractory gastroesophageal cancer

AU - Chao, Joseph

AU - Lin, James

AU - Frankel, Paul

AU - Clark, Andrew J.

AU - Wiley, Devin T.

AU - Garmey, Edward

AU - Fakih, Marwan

AU - Lim, Dean

AU - Chung, Vincent

AU - Luevanos, Eloise

AU - Eliasof, Scott

AU - Davis, Mark E.

AU - Yen, Yun

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Background: CRLX101 is an investigational nanoparticle-drug conjugate with a camptothecin payload. Preclinical evidence indicated preferential uptake in tumors, and tumor xenograft models demonstrate superiority of CRLX101 over irinotecan. A pilot trial was conducted at recommended phase 2 dosing (RP2D) using the bimonthly schedule to assess preferential uptake of CRLX101 in tumor vs. adjacent normal tissue in endoscopically accessible tumors in chemotherapy-refractory gastroesophageal cancer. Results from the biopsies were previously reported and herein we present the clinical outcomes. Methods: Patients initiated CRLX101 dosed at RP2D (15 mg/m2) on days 1 and 15 of a 28-day cycle. Detection of preferential CRLX101 tumor uptake was the primary endpoint and objective response rate (ORR) was a secondary endpoint. With a sample size of ten patients, the study had 90% power to detect ≥1 responder if the true response rate is ≥21%. Results: Between Dec. 2012 and Dec. 2014, ten patients with chemotherapy-refractory (median 2 prior lines of therapy, range 1-4) gastric adenocarcinoma were enrolled. The median time-to-progression was 1.7 months. Best response was seen in one patient with stable disease (SD) for 8 cycles. Only ≥ grade 3 drugrelated toxicity occurred in one patient with grade 3 cardiac chest pain who was able to resume therapy after CRLX101 was reduced to 12 mg/m2. Conclusions: Bimonthly CRLX101 demonstrated minimal activity with SD as best response in this heavily pretreated population. Future efforts with CRLX101 in gastric cancer should focus on combination and more dose-intensive strategies given its favorable toxicity profile and evidence of preferential tumor uptake.

AB - Background: CRLX101 is an investigational nanoparticle-drug conjugate with a camptothecin payload. Preclinical evidence indicated preferential uptake in tumors, and tumor xenograft models demonstrate superiority of CRLX101 over irinotecan. A pilot trial was conducted at recommended phase 2 dosing (RP2D) using the bimonthly schedule to assess preferential uptake of CRLX101 in tumor vs. adjacent normal tissue in endoscopically accessible tumors in chemotherapy-refractory gastroesophageal cancer. Results from the biopsies were previously reported and herein we present the clinical outcomes. Methods: Patients initiated CRLX101 dosed at RP2D (15 mg/m2) on days 1 and 15 of a 28-day cycle. Detection of preferential CRLX101 tumor uptake was the primary endpoint and objective response rate (ORR) was a secondary endpoint. With a sample size of ten patients, the study had 90% power to detect ≥1 responder if the true response rate is ≥21%. Results: Between Dec. 2012 and Dec. 2014, ten patients with chemotherapy-refractory (median 2 prior lines of therapy, range 1-4) gastric adenocarcinoma were enrolled. The median time-to-progression was 1.7 months. Best response was seen in one patient with stable disease (SD) for 8 cycles. Only ≥ grade 3 drugrelated toxicity occurred in one patient with grade 3 cardiac chest pain who was able to resume therapy after CRLX101 was reduced to 12 mg/m2. Conclusions: Bimonthly CRLX101 demonstrated minimal activity with SD as best response in this heavily pretreated population. Future efforts with CRLX101 in gastric cancer should focus on combination and more dose-intensive strategies given its favorable toxicity profile and evidence of preferential tumor uptake.

KW - Clinical trial

KW - CRLX101

KW - Esophageal cancer

KW - Gastric cancer

UR - http://www.scopus.com/inward/record.url?scp=85036585139&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85036585139&partnerID=8YFLogxK

U2 - 10.21037/jgo.2017.08.10

DO - 10.21037/jgo.2017.08.10

M3 - Article

VL - 8

SP - 962

EP - 969

JO - Journal of Gastrointestinal Oncology

JF - Journal of Gastrointestinal Oncology

SN - 2078-6891

IS - 6

ER -