A Pilot Study, Evaluating the Efficacy of Regulatory T-cell Suppression by Ontak in Metastatic Pancreatic Cancer

NCT00726037 | Terminated Phase 2 Results DMC

• 1 other identifier: 200732
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to determine the duration of T reg suppression in patients with metastatic pancreatic cancer receiving Ontak. The goal is to define the optimal time for future dendritic cell vaccine administration.

Conditions

Metastatic Pancreatic Cancer

Keywords

Denileukin diftitox; Metastatic Pancreatic Cancer; Ontak; Regulatory T-cell

Outcome Measures

Primary Outcomes (1)

• T-reg Suppression From a Fractionated Dose of Ontak in Patients With Metastatic Pancreatic Cancer

  The duration of T reg suppression from a fractionated dose of Ontak in patients will be measured in patients with metastatic pancreatic cancer.

  days 8, 12 ,19,26 and 33 post administration

Secondary Outcomes (1)

• Optimal Time for Future Dendritic Cell Vaccine Administration

  33 Days

Study Arms (1)

1

EXPERIMENTAL

Three doses of Ontak 9 mcg/Kg IV over 30 minutes every other day for 1 week

Drug: Ontak

Interventions

Ontak DRUG

One dose of Ontak 9 mcg/Kg IV over 30 minutes times 3 doses. 1 dose every other day

Also known as: Denileukin diftitox

1

Eligibility Criteria

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

You may qualify if:

• Male patients and nonpregnant, nonlactating female patient \> 18 years old
• Histologic diagnosis of pancreatic cancer with distant disease seen on CT or MRI with no prior chemotherapy or radiotherapy for a least 4 weeks
• Karnofsky performance status equal to or greater than 70%
• Life expectancy of at least 3 months.
• No uncontrolled pain
• No symptoms of bowel obstruction
• Women with child bearing potential must agree to use adequate contraceptives. If she should become pregnant she needs to inform the treating physician
• Ability to give informed consent

You may not qualify if:

• Positive serologic testing for HIV, AIDS, human T-cell lymphotrophic virus type 1, hepatitis B, or hepatitis C.
• Hemoglobin \<9g/dL; hematocrit \<27%; platelets \<100,000/ U/L without transfusion support
• Creatinine \> 1.8 mg/dL
• Serum albumin \< 2.0 mg/dL
• AST \> 3X ULN; ALT \> 3X ULN
• Bilirubin \> 1.8
• Uncontrolled angina, arrhythmias, bronchospasm, hypertension, or hypercalcemia.
• Corticosteroid use within 28 days
• Chemotherapy or radiation within 28 days
• Bacteremia or other signs of active systemic infection
• History of autoimmune disease

Sponsors & Collaborators

• Loyola University: lead
• Riveria Country Club Organization: collaborator
• Eisai Inc.: collaborator

Study Sites (1)

Loyola Univeristy Medical Center, Cardinal Bernardin Cancer Center

Maywood, Illinois, 60153, United States

Location

Related Publications (15)

• Conlon KC, Klimstra DS, Brennan MF. Long-term survival after curative resection for pancreatic ductal adenocarcinoma. Clinicopathologic analysis of 5-year survivors. Ann Surg. 1996 Mar;223(3):273-9. doi: 10.1097/00000658-199603000-00007.

  PMID: 8604907 BACKGROUND

• Sperti C, Pasquali C, Piccoli A, Pedrazzoli S. Survival after resection for ductal adenocarcinoma of the pancreas. Br J Surg. 1996 May;83(5):625-31. doi: 10.1002/bjs.1800830512.

  PMID: 8689203 BACKGROUND

• Warshaw AL, Fernandez-del Castillo C. Pancreatic carcinoma. N Engl J Med. 1992 Feb 13;326(7):455-65. doi: 10.1056/NEJM199202133260706. No abstract available.

  PMID: 1732772 BACKGROUND

• Zwar TD, van Driel IR, Gleeson PA. Guarding the immune system: suppression of autoimmunity by CD4+CD25+ immunoregulatory T cells. Immunol Cell Biol. 2006 Dec;84(6):487-501. doi: 10.1111/j.1440-1711.2006.01471.x. Epub 2006 Sep 5.

  PMID: 16956386 BACKGROUND

• Knutson KL, Disis ML, Salazar LG. CD4 regulatory T cells in human cancer pathogenesis. Cancer Immunol Immunother. 2007 Mar;56(3):271-85. doi: 10.1007/s00262-006-0194-y. Epub 2006 Jul 4.

  PMID: 16819631 BACKGROUND

• Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M, Zhu Y, Wei S, Kryczek I, Daniel B, Gordon A, Myers L, Lackner A, Disis ML, Knutson KL, Chen L, Zou W. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med. 2004 Sep;10(9):942-9. doi: 10.1038/nm1093. Epub 2004 Aug 22.

  PMID: 15322536 BACKGROUND

• Woo EY, Yeh H, Chu CS, Schlienger K, Carroll RG, Riley JL, Kaiser LR, June CH. Cutting edge: Regulatory T cells from lung cancer patients directly inhibit autologous T cell proliferation. J Immunol. 2002 May 1;168(9):4272-6. doi: 10.4049/jimmunol.168.9.4272.

  PMID: 11970966 BACKGROUND

• Griffiths RW, Elkord E, Gilham DE, Ramani V, Clarke N, Stern PL, Hawkins RE. Frequency of regulatory T cells in renal cell carcinoma patients and investigation of correlation with survival. Cancer Immunol Immunother. 2007 Nov;56(11):1743-53. doi: 10.1007/s00262-007-0318-z. Epub 2007 May 9.

  PMID: 17487490 BACKGROUND

• Dietl J, Engel JB, Wischhusen J. The role of regulatory T cells in ovarian cancer. Int J Gynecol Cancer. 2007 Jul-Aug;17(4):764-70. doi: 10.1111/j.1525-1438.2006.00861.x. Epub 2007 Feb 16.

  PMID: 17309663 BACKGROUND

• Linehan DC, Goedegebuure PS. CD25+ CD4+ regulatory T-cells in cancer. Immunol Res. 2005;32(1-3):155-68. doi: 10.1385/IR:32:1-3:155.

  PMID: 16106066 BACKGROUND

• Viehl CT, Moore TT, Liyanage UK, Frey DM, Ehlers JP, Eberlein TJ, Goedegebuure PS, Linehan DC. Depletion of CD4+CD25+ regulatory T cells promotes a tumor-specific immune response in pancreas cancer-bearing mice. Ann Surg Oncol. 2006 Sep;13(9):1252-8. doi: 10.1245/s10434-006-9015-y. Epub 2006 Sep 3.

  PMID: 16952047 BACKGROUND

• Ikemoto T, Yamaguchi T, Morine Y, Imura S, Soejima Y, Fujii M, Maekawa Y, Yasutomo K, Shimada M. Clinical roles of increased populations of Foxp3+CD4+ T cells in peripheral blood from advanced pancreatic cancer patients. Pancreas. 2006 Nov;33(4):386-90. doi: 10.1097/01.mpa.0000240275.68279.13.

  PMID: 17079944 BACKGROUND

• Hiraoka N, Onozato K, Kosuge T, Hirohashi S. Prevalence of FOXP3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions. Clin Cancer Res. 2006 Sep 15;12(18):5423-34. doi: 10.1158/1078-0432.CCR-06-0369.

  PMID: 17000676 BACKGROUND

• Figgitt DP, Lamb HM, Goa KL. Denileukin diftitox. Am J Clin Dermatol. 2000 Jan-Feb;1(1):67-72; discussion 73. doi: 10.2165/00128071-200001010-00008.

  PMID: 11702307 BACKGROUND

• Dannull J, Su Z, Rizzieri D, Yang BK, Coleman D, Yancey D, Zhang A, Dahm P, Chao N, Gilboa E, Vieweg J. Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells. J Clin Invest. 2005 Dec;115(12):3623-33. doi: 10.1172/JCI25947. Epub 2005 Nov 23.

  PMID: 16308572 BACKGROUND

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

denileukin diftitox

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Limitations and Caveats

This study was prematurely terminated, because the study drug Ontak is no longer supplied by the manufacturer for this study. Data is not analyzed for any outcome measures.

Results Point of Contact

• Title: Margret Shoup
• Organization: Northwestern Medicine Regional Medical Group

MSHOUP@lumc.edu

630-352-5450

Study Officials

• Margo Shoup, MD

  Loyola University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2008
• First Posted: July 31, 2008
• Study Start: October 1, 2008
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: September 29, 2016
• Results First Posted: August 24, 2016

Record last verified: 2016-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)