Trial of Intraperitoneal (IP) Oxaliplatin in Combination With Intravenous FOLFIRI

Phase I Trial of Intraperitoneal Oxaliplatin in Combination With Intravenous FOLFIRI (5-fluorouracil, Leucovorin and Irinotecan) for Peritoneal Carcinomatosis From Colorectal and Appendiceal Cancer

This is a Phase I dose escalation study to determine how much chemotherapy can be safely administered into the abdomen while experiencing the fewest possible side effects.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Peritoneal Carcinomatosis; Appendix Cancer
• Intervention / Treatment: Drug: Oxaliplatin

Detailed Description

There are two common combinations of chemotherapy drugs used to treat cancer of the colon, rectum, or appendix that has spread to the abdomen. One uses 5-fluorouracil (also called 5-FU), leucovorin and oxaliplatin, and is called FOLFOX. The other uses 5-FU, leucovorin, and irinotecan, and is called FOLFIRI. The Food and Drug Administration (FDA) has approved each of these combinations as treatment for colon or rectal cancer. Each is given through the veins.

FOLFOX and FOLFIRI do not work well for tumors growing in the abdominal cavity. The investigators are trying to determine if giving chemotherapy called oxaliplatin directly into the abdominal cavity will have a greater effect on the cancer.

The FDA has approved oxaliplatin to be given to people through their veins to treat advanced colorectal cancer. Giving oxaliplatin directly into the abdomen in this study is experimental and is not approved by the FDA. This study will give the standard chemotherapy FOLFIRI through the veins and oxaliplatin directly into the abdomen. This is the first time intraperitoneal oxaliplatin is being given in combination with FOLFIRI.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • UMass Memorial Medical Center - University Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Must be 18 years of age or older and capable of providing informed consent indicating awareness of the investigational nature of this trial, in keeping with institutional policy
• Must consent to participate in the trial and have signed an approved informed consent form conforming to institutional policy
• Must have histopathologically or cytologically confirmed colon, rectal or appendiceal adenocarcinoma with synchronous or metachronous peritoneal dissemination of disease.(Stage IV peritoneal based disease only)
• Must have active measurable disease by either abdominal computerized axial tomography (CT)/ Magnetic resonance imaging (MRI) or laparoscopy.

Adequate laboratory values

• Absolute neutrophil count (ANC) > 1200/10*3/uL
• Platelet count > 140,000/10*3/uL
• Total serum bilirubin ≤ 1.5 mg/dl (patients with total bilirubin >1.5 mg/dL are eligible only with Gilbert's syndrome)
• Alkaline phosphatase < 2.5 times the upper limit of normal (ULN) (alkaline phosphatase and AST cannot both exceed the ULN)
• Aspartate aminotransferase (AST) < 1.5 times the ULN (alkaline phosphatase and AST cannot both exceed the ULN)
• Serum renal function parameters (BUN and creatinine) are within normal limits (eGFR) >50)
• Satisfactory cardiopulmonary function (as determined by Physician)
• Patients can have received prior systemic chemotherapy, radiation or surgery
• Patients must be able to undergo placement of an intraperitoneal (IP) catheter and a Port-A Cath, if not already present
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
• Women of reproductive age and men who are sexually active must be willing to practice effective contraception
• Patients will be allowed to have secondary malignancies as long as they do not require active concomitant treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Dose Escalation; Single arm dose finding for intraperitoneal Oxaliplatin. All patients will receive experimental treatment. The first cohort of 3 patients will receive dose level 1. The second cohort of 3 patients will receive dose level 2. The Third cohort of 3 patients will receive dose level 3. The fourth cohort of 3 patients will receive dose level 2.

Drug: Oxaliplatin; Intraperitoneal oxaliplatin will be given along with standard chemotherapy FOLFIRI. Level 1: Oxaliplatin 25mg/m2 IP every 2 weeks on day #1 of chemotherapy . Level 2: Oxaliplatin 55mg/m2 IP every 2 weeks on day #1 of chemotherapy Level 3: Oxaliplatin 85mg/m2 IP every 2 weeks on day #1 of chemotherapy Level 4: Oxaliplatin 55 mg/m2 IP every 2 weeks on day #1 of chemotherapy (due to DLTs found)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Define the maximum tolerated dose (MTD) of intraperitoneal (IP) oxaliplatin given with systemic FOLFIRI in patients with peritoneal carcinomatosis (PC) of colorectal or appendiceal origin	8 weeks

Collaborators and Investigators

• Sponsor: University of Massachusetts, Worcester
• Investigators: Principal Investigator: Bradley Switzer, MD, University of Massachusetts, Worcester

Publications and helpful links

General Publications

• Armstrong DK, Bundy B, Wenzel L, Huang HQ, Baergen R, Lele S, Copeland LJ, Walker JL, Burger RA; Gynecologic Oncology Group. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006 Jan 5;354(1):34-43. doi: 10.1056/NEJMoa052985.
• Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
• Falcone A, Ricci S, Brunetti I, Pfanner E, Allegrini G, Barbara C, Crino L, Benedetti G, Evangelista W, Fanchini L, Cortesi E, Picone V, Vitello S, Chiara S, Granetto C, Porcile G, Fioretto L, Orlandini C, Andreuccetti M, Masi G; Gruppo Oncologico Nord Ovest. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol. 2007 May 1;25(13):1670-6. doi: 10.1200/JCO.2006.09.0928.
• Loupakis F, Cremolini C, Masi G, Lonardi S, Zagonel V, Salvatore L, Cortesi E, Tomasello G, Ronzoni M, Spadi R, Zaniboni A, Tonini G, Buonadonna A, Amoroso D, Chiara S, Carlomagno C, Boni C, Allegrini G, Boni L, Falcone A. Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N Engl J Med. 2014 Oct 23;371(17):1609-18. doi: 10.1056/NEJMoa1403108.
• Franko J, Shi Q, Goldman CD, Pockaj BA, Nelson GD, Goldberg RM, Pitot HC, Grothey A, Alberts SR, Sargent DJ. Treatment of colorectal peritoneal carcinomatosis with systemic chemotherapy: a pooled analysis of north central cancer treatment group phase III trials N9741 and N9841. J Clin Oncol. 2012 Jan 20;30(3):263-7. doi: 10.1200/JCO.2011.37.1039. Epub 2011 Dec 12.
• Elias D, Lefevre JH, Chevalier J, Brouquet A, Marchal F, Classe JM, Ferron G, Guilloit JM, Meeus P, Goere D, Bonastre J. Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. J Clin Oncol. 2009 Feb 10;27(5):681-5. doi: 10.1200/JCO.2008.19.7160. Epub 2008 Dec 22.
• Sadeghi B, Arvieux C, Glehen O, Beaujard AC, Rivoire M, Baulieux J, Fontaumard E, Brachet A, Caillot JL, Faure JL, Porcheron J, Peix JL, Francois Y, Vignal J, Gilly FN. Peritoneal carcinomatosis from non-gynecologic malignancies: results of the EVOCAPE 1 multicentric prospective study. Cancer. 2000 Jan 15;88(2):358-63. doi: 10.1002/(sici)1097-0142(20000115)88:23.0.co;2-o.
• Fajardo AD, Tan B, Reddy R, Fleshman J. Delayed repeated intraperitoneal chemotherapy after cytoreductive surgery for colorectal and appendiceal carcinomatosis. Dis Colon Rectum. 2012 Oct;55(10):1044-52. doi: 10.1097/DCR.0b013e318265ad42.
• Elias D, Bonnay M, Puizillou JM, Antoun S, Demirdjian S, El OA, Pignon JP, Drouard-Troalen L, Ouellet JF, Ducreux M. Heated intra-operative intraperitoneal oxaliplatin after complete resection of peritoneal carcinomatosis: pharmacokinetics and tissue distribution. Ann Oncol. 2002 Feb;13(2):267-72. doi: 10.1093/annonc/mdf019.
• Elias D, Matsuhisa T, Sideris L, Liberale G, Drouard-Troalen L, Raynard B, Pocard M, Puizillou JM, Billard V, Bourget P, Ducreux M. Heated intra-operative intraperitoneal oxaliplatin plus irinotecan after complete resection of peritoneal carcinomatosis: pharmacokinetics, tissue distribution and tolerance. Ann Oncol. 2004 Oct;15(10):1558-65. doi: 10.1093/annonc/mdh398.
• Gervais MK, Dube P, McConnell Y, Drolet P, Mitchell A, Sideris L. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy with oxaliplatin for peritoneal carcinomatosis arising from colorectal cancer. J Surg Oncol. 2013 Dec;108(7):438-43. doi: 10.1002/jso.23431. Epub 2013 Sep 9.
• Ceelen W, De Somer F, Van Nieuwenhove Y, Vande Putte D, Pattyn P. Effect of perfusion temperature on glucose and electrolyte transport during hyperthermic intraperitoneal chemoperfusion (HIPEC) with oxaliplatin. Eur J Surg Oncol. 2013 Jul;39(7):754-9. doi: 10.1016/j.ejso.2012.07.120. Epub 2012 Aug 9.
• Mehta AM, Van den Hoven JM, Rosing H, Hillebrand MJ, Nuijen B, Huitema AD, Beijnen JH, Verwaal VJ. Stability of oxaliplatin in chloride-containing carrier solutions used in hyperthermic intraperitoneal chemotherapy. Int J Pharm. 2015 Feb 1;479(1):23-7. doi: 10.1016/j.ijpharm.2014.12.025. Epub 2014 Dec 20.
• Fuchs CS, Marshall J, Mitchell E, Wierzbicki R, Ganju V, Jeffery M, Schulz J, Richards D, Soufi-Mahjoubi R, Wang B, Barrueco J. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C Study. J Clin Oncol. 2007 Oct 20;25(30):4779-86. doi: 10.1200/JCO.2007.11.3357.
• Teefey P, Bou Zgheib N, Apte SM, Gonzalez-Bosquet J, Judson PL, Roberts WS, Lancaster JM, Wenham RM. Factors associated with improved toxicity and tolerability of intraperitoneal chemotherapy in advanced-stage epithelial ovarian cancers. Am J Obstet Gynecol. 2013 Jun;208(6):501.e1-7. doi: 10.1016/j.ajog.2013.03.012. Epub 2013 Mar 15.

Helpful Links

• Colon Cancer 2014
• Cancer Facts and Figures 2015

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (ACTUAL): February 1, 2022
• Study Completion (ACTUAL): February 1, 2022

Study Registration Dates

• First Submitted: July 12, 2016
• First Submitted That Met QC Criteria: July 13, 2016
• First Posted (ESTIMATE): July 14, 2016

Study Record Updates

• Last Update Posted (ACTUAL): May 31, 2022
• Last Update Submitted That Met QC Criteria: May 27, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Peritoneal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Abdominal Neoplasms; Cecal Diseases; Cecal Neoplasms; Carcinoma; Peritoneal Neoplasms; Appendiceal Neoplasms; Antineoplastic Agents; Oxaliplatin
• Other Study ID Numbers: H00008477

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes