Metastatic Pancreatic CancerPhase 2NCT00726037
A Pilot Study, Evaluating the Efficacy of Regulatory T-cell Suppression by Ontak in Metastatic Pancreatic Cancer
A Phase 2 study testing Ontak in people with Metastatic Pancreatic Cancer, run by Loyola University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Pancreatic Cancer
- What is being tested?
- Ontak
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2008to Jan 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Loyola Univeristy Medical Center, Cardinal Bernardin Cancer Center
Maywood, Illinois, 60153
About this study
Official title: A Pilot Study Evaluating the Efficacy of Regulatory T-cell (T-reg) Suppression by Denileukin Diftitox (Ontak) in Metastatic Pancreatic Cancer
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.
Read the detailed description
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
- Metastatic Pancreatic Cancer
- Being tested
- Ontak
- Keywords
- Denileukin diftitox, Metastatic Pancreatic Cancer, Ontak, Regulatory T-cell
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OntakDrug
Also called Denileukin diftitox
One dose of Ontak 9 mcg/Kg IV over 30 minutes times 3 doses. 1 dose every other day
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Three doses of Ontak 9 mcg/Kg IV over 30 minutes every other day for 1 week Receives: Drug: Ontak |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: days 8, 12 ,19,26 and 33 post administration
Secondary outcomes (1)
Optimal Time for Future Dendritic Cell Vaccine Administration
The goal is to define the optimal time with 95% sensitivity and 95% specificity for future dendritic cell vaccine administration
Measured: 33 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2008 (estimated)
- Study startOct 2008
- Primary completionJan 2012
- Study completionJan 2012
Why it stopped: Collaborator withdrew support due to a drug supply interruption.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Metastatic Pancreatic CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Loyola University
- Sponsor type
- University, hospital or other
- Collaborators
- Riveria Country Club Organization, Eisai Inc.
- Responsible party
- Sponsor
- Investigators
- Margo Shoup, MD, Principal investigator, Loyola University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00726037
- Sponsor's protocol ID
- 200732
- Status last verified
- Aug 2016
- First submitted
- 29 Jul 2008
- Last updated
- 29 Sep 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 8604907Sperti 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.
PubMed 8689203Warshaw 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.
PubMed 1732772Zwar 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.
PubMed 16956386Knutson 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.
PubMed 16819631Curiel 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.
PubMed 15322536Woo 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.
PubMed 11970966Griffiths 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.
PubMed 17487490Dietl 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.
PubMed 17309663Linehan 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.
PubMed 16106066Viehl 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.
PubMed 16952047Ikemoto 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.
PubMed 17079944Hiraoka 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.
PubMed 17000676Figgitt 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.
PubMed 11702307Dannull 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.
PubMed 16308572
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study Evaluating the Efficacy of Regulatory T-cell (T-reg) Suppression by Denileukin Diftitox (Ontak) in Metastatic Pancreatic Cancer
- ClinicalTrials.gov ID
- NCT00726037
- Acronym / sponsor ID
- 200732
- Conditions
- Metastatic Pancreatic Cancer
- Keywords
- Denileukin diftitox, Metastatic Pancreatic Cancer, Ontak, Regulatory T-cell
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Collaborator withdrew support due to a drug supply interruption.
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Loyola UniversityUniversity, hospital or other
- Collaborators
- Riveria Country Club Organization, Eisai Inc.
- Study start
- Oct 2008
- Primary completion
- Jan 2012 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 31 Jul 2008 (estimated)
- Results
- Posted 24 Aug 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: OntakThree doses of Ontak 9 mcg/Kg IV over 30 minutes every other day for 1 week |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OntakAlso: Denileukin diftitoxOne dose of Ontak 9 mcg/Kg IV over 30 minutes times 3 doses. 1 dose every other day | Drug | 1 |
Primary outcome
T-reg Suppression From a Fractionated Dose of Ontak in Patients With Metastatic Pancreatic Cancer
Time frame: days 8, 12 ,19,26 and 33 post administration
The duration of T reg suppression from a fractionated dose of Ontak in patients will be measured in patients with metastatic pancreatic cancer.
1 secondary outcome
Optimal Time for Future Dendritic Cell Vaccine Administration
Time frame: 33 Days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 8604907Conlon 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.
- Background: PubMed 8689203Sperti 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.
- Background: PubMed 1732772Warshaw 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.
- Background: PubMed 16956386Zwar 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.
- Background: PubMed 16819631Knutson 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.
- Background: PubMed 15322536Curiel 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.
- Background: PubMed 11970966Woo 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.
- Background: PubMed 17487490Griffiths 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.
- Background: PubMed 17309663Dietl 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.
- Background: PubMed 16106066Linehan 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.
- Background: PubMed 16952047Viehl 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.
- Background: PubMed 17079944Ikemoto 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Margo Shoup, MD principal investigator
Loyola University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ontak in people with Metastatic Pancreatic Cancer, run by Loyola University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 29 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Aug 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
T-reg Suppression From a Fractionated Dose of Ontak in Patients With Metastatic Pancreatic Cancer (time frame: days 8, 12 ,19,26 and 33 post administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00726037, which also lists 15 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2016.