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

NCT ID: NCT00726037

Last Updated: 2016-09-29

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

7 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-10-31

Study Completion Date

2012-01-31

Brief Summary

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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.

Detailed Description

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Despite improved insight into the epidemiology and biology, pancreatic cancer remains a significant health problem as evidenced by the disappointing survival rates associated with advanced disease. Because of its aggressive growth and early metastatic dissemination, only 20% of patients can be treated by surgery at the time of diagnosis. Furthermore, the overall 5-year survival rate of stage IV disease is \< 5% \[1-3\] despite chemotherapy. With such a dismal outlook, it is obvious that novel treatment strategies are required.

There is limited experience in the literature with the use of Ontak in the treatment of metastatic pancreatic cancer. Viehl, et al, demonstrated in a murine model of pancreatic cancer, that ontak combined with whole tumor vaccine led to a significantly increased T cell-dependent antitumor immune response, as well as an improved survival compared to controls. Our group has an active trial at Loyola evaluating the role of dendritic cell vaccine in patients with unresectable, not metastatic, pancreatic cancer. Preliminary data suggests a correlation with time to progression and restoration of Tregs following an initial decrease after the DC injection. The goal of the current proposal is to determine the time point at which the Tregs reach the nadir within four weeks of ontak injection. When this is determined, we will eventually propose administering ontak followed by DC vaccine at the nadir Treg time point for patients with unresectable pancreatic cancer

Conditions

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Metastatic Pancreatic Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1

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

Group Type EXPERIMENTAL

Ontak

Intervention Type DRUG

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

Interventions

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Ontak

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

Intervention Type DRUG

Other Intervention Names

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Denileukin diftitox

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Riveria Country Club Organization

UNKNOWN

Sponsor Role collaborator

Eisai Inc.

INDUSTRY

Sponsor Role collaborator

Loyola University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Margo Shoup, MD

Role: PRINCIPAL_INVESTIGATOR

Loyola University

Locations

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Loyola Univeristy Medical Center, Cardinal Bernardin Cancer Center

Maywood, Illinois, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 8604907 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8689203 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 1732772 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16956386 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16819631 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15322536 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11970966 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17487490 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17309663 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16106066 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16952047 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17079944 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17000676 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11702307 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16308572 (View on PubMed)

Other Identifiers

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200732

Identifier Type: -

Identifier Source: org_study_id

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