Trial of Intraperitoneal (IP) Oxaliplatin in Combination With Intravenous FOLFIRI
Primary Purpose
Colorectal Cancer, Appendix Cancer, Peritoneal Carcinomatosis
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Oxaliplatin
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer
Eligibility Criteria
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
Sites / Locations
- UMass Memorial Medical Center - University Campus
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Dose Escalation
Arm Description
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.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Full Information
NCT ID
NCT02833753
First Posted
July 12, 2016
Last Updated
May 27, 2022
Sponsor
University of Massachusetts, Worcester
1. Study Identification
Unique Protocol Identification Number
NCT02833753
Brief Title
Trial of Intraperitoneal (IP) Oxaliplatin in Combination With Intravenous FOLFIRI
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
July 2016 (undefined)
Primary Completion Date
February 2022 (Actual)
Study Completion Date
February 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Massachusetts, Worcester
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer, Appendix Cancer, Peritoneal Carcinomatosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
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.
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dose Escalation
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Intervention Description
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)
Primary Outcome Measure Information:
Title
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
Time Frame
8 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bradley Switzer, MD
Organizational Affiliation
University of Massachusetts, Worcester
Official's Role
Principal Investigator
Facility Information:
Facility Name
UMass Memorial Medical Center - University Campus
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
17470860
Citation
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.
Results Reference
background
PubMed Identifier
25337750
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.
Results Reference
background
PubMed Identifier
22162570
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.
Results Reference
background
PubMed Identifier
19103728
Citation
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.
Results Reference
background
PubMed Identifier
10640968
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, 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.
Results Reference
background
PubMed Identifier
16394300
Citation
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.
Results Reference
background
PubMed Identifier
22965403
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.
Results Reference
background
PubMed Identifier
11886004
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. doi: 10.1093/annonc/mdf019.
Results Reference
background
PubMed Identifier
15367418
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. doi: 10.1093/annonc/mdh398.
Results Reference
background
PubMed Identifier
24018983
Citation
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.
Results Reference
background
PubMed Identifier
22878060
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.
Results Reference
background
PubMed Identifier
25535649
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.
Results Reference
background
PubMed Identifier
17947725
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. doi: 10.1200/JCO.2007.11.3357.
Results Reference
background
PubMed Identifier
23507546
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.
Results Reference
background
PubMed Identifier
19097774
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.
Results Reference
background
Learn more about this trial
Trial of Intraperitoneal (IP) Oxaliplatin in Combination With Intravenous FOLFIRI
We'll reach out to this number within 24 hrs