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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 7/2017

01-07-2017 | Colorectal Cancer

Novel Treatment with Intraperitoneal MOC31PE Immunotoxin in Colorectal Peritoneal Metastasis: Results From the ImmunoPeCa Phase 1 Trial

Authors: Ida S. Frøysnes, MD, Yvonne Andersson, PhD, Stein G. Larsen, MD, PhD, Ben Davidson, MD, PhD, Janne-Merete Torset Øien, MSc, Kari Hauge Olsen, BSc, Karl-Erik Giercksky, MD, PhD, Lars Julsrud, MD, Øystein Fodstad, MD, PhD, Svein Dueland, MD, PhD, Kjersti Flatmark, MD, PhD

Published in: Annals of Surgical Oncology | Issue 7/2017

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Abstract

Background

MOC31PE immunotoxin was developed to rapidly kill cells expressing the tumor-associated epithelial cell adhesion molecule, which is highly expressed in colorectal cancer. Although cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may offer long-term survival to patients with peritoneal metastasis from colorectal cancer (PM-CRC), most patients experience disease relapse and novel therapeutic options are needed. On this basis, MOC31PE is being developed as a novel therapeutic principle to target PM-CRC.

Methods

This was a dose-escalating phase I trial to evaluate the safety and toxicity (primary endpoint), pharmacokinetic profile, and neutralizing antibody response (secondary endpoints) upon intraperitoneal administration of MOC31PE in patients with PM-CRC undergoing CRS-HIPEC with Mitomycin C. Fifteen patients received the study drug at four dose levels (3+3+3+6), administered intraperitoneally as a single dose the day after CRS-HIPEC.

Results

No dose-limiting toxicity was observed, and the maximum tolerated dose was not reached. There was negligible systemic absorption of the study drug. Drug concentrations in peritoneal fluid samples were in the cytotoxic range and increased in a dose-dependent manner. MOC31PE recovered from peritoneal cavity retained its cytotoxic activity in cell-based assays. All patients developed neutralizing antibodies.

Conclusions

Intraperitoneal administration of MOC31PE was safe and well tolerated, and combined with low systemic uptake, MOC31PE seems ideal for local intraperitoneal treatment. The drug will be further evaluated in an ongoing phase II expansion cohort.
Appendix
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Literature
1.
van Gestel YR, Thomassen I, Lemmens VE, et al. Metachronous peritoneal carcinomatosis after curative treatment of colorectal cancer. Eur J Surg Oncol. 2014;40:963–9.CrossRefPubMed
2.
Jayne DG, Fook S, Loi C, Seow-Choen F. Peritoneal carcinomatosis from colorectal cancer. Br J Surg. 2002;89:1545–50.CrossRefPubMed
3.
Sadeghi B, Arvieux C, Glehen O, et al. Peritoneal carcinomatosis from non-gynecologic malignancies: results of the EVOCAPE 1 multicentric prospective study. Cancer. 2000;88:358–63.CrossRefPubMed
4.
Sugarbaker PH. Peritoneum as the first-line of defense in carcinomatosis. J Surg Oncol. 2007;95:93–6.CrossRefPubMed
5.
Dedrick RL, Myers CE, Bungay PM, DeVita VT Jr. Pharmacokinetic rationale for peritoneal drug administration in the treatment of ovarian cancer. Cancer Treat Rep. 1978;62:1–11.PubMed
6.
Sugarbaker PH, Van der Speeten K, Stuart OA. Pharmacologic rationale for treatments of peritoneal surface malignancy from colorectal cancer. World J Gastrointest Oncol. 2010;2:19–30.CrossRefPubMedPubMedCentral
7.
Verwaal VJ, Bruin S, Boot H, van Slooten G, van Tinteren H. 8-Year follow-up of randomized trial: cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy in patients with peritoneal carcinomatosis of colorectal cancer. Ann Surg Oncol. 2008;15:2426–32.CrossRefPubMed
8.
Mahteme H, Hansson J, Berglund A, et al. Improved survival in patients with peritoneal metastases from colorectal cancer: a preliminary study. Br J Cancer. 2004;90:403–7.CrossRefPubMedPubMedCentral
9.
Elias D, Lefevre JH, Chevalier J, et al. Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. J Clin Oncol. 2009;27:681–5.CrossRefPubMed
10.
Franko J, Ibrahim Z, Gusani NJ, Holtzman MP, Bartlett DL, Zeh HJ III. Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion versus systemic chemotherapy alone for colorectal peritoneal carcinomatosis. Cancer. 2010;116:3756–62.CrossRefPubMed
11.
Mirnezami R, Moran BJ, Harvey K, et al. Cytoreductive surgery and intraperitoneal chemotherapy for colorectal peritoneal metastases. World J Gastroenterol. 2014;20:14018–32.CrossRefPubMedPubMedCentral
12.
Froysnes IS, Larsen SG, Spasojevic M, Dueland S, Flatmark K. Complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastasis in Norway: prognostic factors and oncologic outcome in a national patient cohort. J Surg Oncol. 2016;14(1):222-7.CrossRef
13.
Andersson Y, Engebraaten O, Fodstad O. Synergistic anti-cancer effects of immunotoxin and cyclosporin in vitro and in vivo. Br J Cancer. 2009;101:1307–15.CrossRefPubMedPubMedCentral
14.
Andersson Y, Juell S, Fodstad O. Downregulation of the antiapoptotic MCL-1 protein and apoptosis in MA-11 breast cancer cells induced by an anti-epidermal growth factor receptor-Pseudomonas exotoxin a immunotoxin. Int J Cancer. 2004;112:475–83.CrossRefPubMed
15.
Went P, Vasei M, Bubendorf L, et al. Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate, and lung cancers. Br J Cancer. 2006;94:128–35.CrossRefPubMedPubMedCentral
16.
Went PT, Lugli A, Meier S, et al. Frequent EpCam protein expression in human carcinomas. Hum Pathol. 2004;35:122–8.CrossRefPubMed
17.
Heiss MM, Murawa P, Koralewski P, et al. The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: results of a prospective randomized phase II/III trial. Int J Cancer. 2010;127:2209–21.CrossRefPubMedPubMedCentral
18.
Punt CJ, Nagy A, Douillard JY, et al. Edrecolomab alone or in combination with fluorouracil and folinic acid in the adjuvant treatment of stage III colon cancer: a randomised study. Lancet. 2002;360:671–7.CrossRefPubMed
19.
Flatmark K, Guldvik IJ, Svensson H, et al. Immunotoxin targeting EpCAM effectively inhibits peritoneal tumor growth in experimental models of mucinous peritoneal surface malignancies. Int J Cancer. 2013;133:1497–506.CrossRefPubMed
20.
Wiiger MT, Bideli H, Fodstad O, Flatmark K, Andersson Y. The MOC31PE immunotoxin reduces cell migration and induces gene expression and cell death in ovarian cancer cells. J Ovarian Res. 2014;7:23.CrossRefPubMedPubMedCentral
21.
Andersson Y, Engebraaten O, Juell S, et al. Phase I trial of EpCAM-targeting immunotoxin MOC31PE, alone and in combination with cyclosporin. Br J Cancer. 2015;113:1548–55.CrossRefPubMedPubMedCentral
22.
Sorensen O, Flatmark K, Reed W, et al. Evaluation of complete cytoreductive surgery and two intraperitoneal chemotherapy techniques in pseudomyxoma peritonei. EJSO Eur J Surg Oncol. 2012;38:969–76.CrossRefPubMed
23.
Strasberg SM, Linehan DC, Hawkins WG. The accordion severity grading system of surgical complications. Ann Surg. 2009;250:177–86.CrossRefPubMed
24.
Engebraaten O, Sivam G, Juell S, Fodstad O. Systemic immunotoxin treatment inhibits formation of human breast cancer metastasis and tumor growth in nude rats. Int J Cancer. 2000;88:970–6.CrossRefPubMed
25.
Sivendran S, Latif A, McBride RB, et al. Adverse event reporting in cancer clinical trial publications. J Clin Oncol. 2014;32:83–9.CrossRefPubMed
26.
Flessner MF. The transport barrier in intraperitoneal therapy. Am J Physiol Renal Physiol. 2005;288:F433–F442.CrossRefPubMed
27.
Ruf P, Kluge M, Jager M, et al. Pharmacokinetics, immunogenicity, and bioactivity of the therapeutic antibody catumaxomab intraperitoneally administered to cancer patients. Br J Clin Pharmacol. 2010;69:617–25.CrossRefPubMedPubMedCentral
28.
Pai LH, Bookman MA, Ozols RF, et al. Clinical evaluation of intraperitoneal Pseudomonas exotoxin immunoconjugate OVB3-PE in patients with ovarian cancer. J Clin Oncol. 1991;9:2095–103.CrossRefPubMed
29.
Krediet RT, Struijk DG, Koomen GC, Hoek FJ, Arisz L. The disappearance of macromolecules from the peritoneal cavity during continuous ambulatory peritoneal dialysis (CAPD) is not dependent on molecular size. Perit Dial Int. 1990;10:147–52.PubMed
Metadata
Title
Novel Treatment with Intraperitoneal MOC31PE Immunotoxin in Colorectal Peritoneal Metastasis: Results From the ImmunoPeCa Phase 1 Trial
Authors
Ida S. Frøysnes, MD
Yvonne Andersson, PhD
Stein G. Larsen, MD, PhD
Ben Davidson, MD, PhD
Janne-Merete Torset Øien, MSc
Kari Hauge Olsen, BSc
Karl-Erik Giercksky, MD, PhD
Lars Julsrud, MD
Øystein Fodstad, MD, PhD
Svein Dueland, MD, PhD
Kjersti Flatmark, MD, PhD
Publication date
01-07-2017
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 7/2017
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-017-5814-6

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