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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02833753
• Other study ID #: H00008477
• Status: Completed
• Phase: Phase 1
• Start date: July 2016
• Est. completion date: February 2022

Study information

• Verified date: May 2022
• Source: University of Massachusetts, Worcester
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: February 2022
• Est. primary completion date: February 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Appendiceal Neoplasms
• Appendix Cancer
• Carcinoma
• Colorectal Cancer
• Peritoneal Carcinomatosis
• Peritoneal Neoplasms

Intervention

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)

Locations

Country	Name	City	State
United States	UMass Memorial Medical Center - University Campus	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
University of Massachusetts, Worcester

Country where clinical trial is conducted

United States, 

References & Publications (15)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Elias D, Lefevre JH, Chevalier J, Brouquet A, Marchal F, Classe JM, Ferron G, Guilloit JM, Meeus P, Goéré 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. — View Citation

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. — View Citation

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. — View Citation

Falcone A, Ricci S, Brunetti I, Pfanner E, Allegrini G, Barbara C, Crinò 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. — View Citation

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. — View Citation

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. — View Citation

Gervais MK, Dubé 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. — View Citation

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. — View Citation

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. — View Citation

Sadeghi B, Arvieux C, Glehen O, Beaujard AC, Rivoire M, Baulieux J, Fontaumard E, Brachet A, Caillot JL, Faure JL, Porcheron J, Peix JL, François 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. — View Citation

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. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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

External Links

•   Cancer Facts and Figures 2015
•   Colon Cancer 2014