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

Metastatic Pancreatic Cancer Clinical Trial

Official title:

A Pilot Study Evaluating the Efficacy of Regulatory T-cell (T-reg) Suppression by Denileukin Diftitox (Ontak) in Metastatic Pancreatic Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00726037
• Other study ID #: 200732
• Status: Terminated
• Phase: Phase 2
• First received: July 29, 2008
• Last updated: October 29, 2012
• Start date: October 2008
• Est. completion date: January 2012

Study information

• Verified date: October 2012
• Source: Loyola University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study is designed to determine the following:

1. 1. The degree and 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

2. 2. To determine the safety of anti-CD4/CD25 monoclonal antibody (Ontak) in patients with metastatic pancreatic cancer

3. 3. To follow patients treated with Ontak for a clinical response as determined by Ca 19-9 and CT scans

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Metastatic Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

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

Locations

Country	Name	City	State
United States	Loyola Univeristy Medical Center, Cardinal Bernardin Cancer Center	Maywood	Illinois

Sponsors (3)

Lead Sponsor	Collaborator
Loyola University	Eisai Inc., Riveria Country Club Organization

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1. To determine the degree and duration of T reg suppression from a fractionated dose of Ontak in patients with metastatic pancreatic cancer, with the goal to define the optimal time for future dendritic cell vaccine administration		days 8, 12 ,19,26 and 33 post administration	No
Secondary	To determine the safety of a single dose of anti-CD4/CD25 monoclonal antibody Ontak) in patients with metastatic pancreatic cancer		lifetime	Yes