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

NCT02833753 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: H00008477
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Colorectal Cancer; Appendix Cancer; Peritoneal Carcinomatosis

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

Dose Escalation

EXPERIMENTAL

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

Interventions

Oxaliplatin DRUG

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)

Dose Escalation

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

Sponsors & Collaborators

• University of Massachusetts, Worcester: lead

Study Sites (1)

UMass Memorial Medical Center - University Campus

Worcester, Massachusetts, 01655, United States

Location

Related Publications (15)

• 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.

  PMID: 17470860 BACKGROUND

• 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.

  PMID: 25337750 BACKGROUND

• 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.

  PMID: 22162570 BACKGROUND

• 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.

  PMID: 19103728 BACKGROUND

• 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.

  PMID: 10640968 BACKGROUND

• 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.

  PMID: 16394300 BACKGROUND

• 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.

  PMID: 22965403 BACKGROUND

• 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.

  PMID: 11886004 BACKGROUND

• 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.

  PMID: 15367418 BACKGROUND

• 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.

  PMID: 24018983 BACKGROUND

• 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.

  PMID: 22878060 BACKGROUND

• 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.

  PMID: 25535649 BACKGROUND

• 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.

  PMID: 17947725 BACKGROUND

• 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.

  PMID: 23507546 BACKGROUND

• 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.

  PMID: 19097774 BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms; Appendiceal Neoplasms; Peritoneal Neoplasms

Interventions

Oxaliplatin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Cecal Neoplasms; Cecal Diseases; Abdominal Neoplasms; Peritoneal Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Study Officials

• Bradley Switzer, MD

  University of Massachusetts, Worcester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Model Details: There are three cohorts of patients: Group #1 is at 25mg/m2 of IP oxaliplatin and has been completed. Group #2 is at 55mg/m2 of IP oxaliplatin is completed. Group #3 is at 85mg/m2 of IP oxaliplatin is currently enrolling. If DLTs found additional 3 subjects will be dosed at the lower dose level cohort. 2 DLTs were found in the 85 mg/m2 cohort therefore 3 additional subjects (Group # 4) will be enrolled to the 55 mg/m2 cohort.

Study Record Dates

• First Submitted: July 12, 2016
• First Posted: July 14, 2016
• Study Start: July 1, 2016
• Primary Completion: February 1, 2022
• Study Completion: February 1, 2022
• Last Updated: May 31, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)