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Phase I Intratumoral Dendritic Cell Immunotherapy in Thermally Ablated Liver Metastases

Primary Purpose

Liver Cancer

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Intratumoral Dendritic Cell Immunotherapy
autologous dendritic cells
Sponsored by
Stanford University
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Liver Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:- Patients must have a histologically confirmed colorectal or neuroendocrine cancer with two or more hepatic metastatic lesions. Patients must have unresectable liver metastasis by virtue of: Bi-lobar disease. Extra-hepatic disease. Patients for whom there are medical contraindications to surgery. Anatomic sites within the liver that in the opinion of our surgeon would likely be left with positive margin. Patient must have a minimum of 2 RFA-eligible lesion in the liver. Such as hepatic lesions that are 5 cm or smaller and that are accessible to RF ablation, which in general excludes sites contiguous with critical structures such as bowel or central bile duct and also those that are not amenable to radiographic localization such as small lesions in the dome of the liver. Extra-hepatic disease will be allowed provided that the liver lesions represent the most life-threatening site for that patient. Examples include sub centimeter asymptomatic lung metastases or asymptomatic retroperitoneal lymph nodes or peritoneal metastases Evaluable disease by CT scan or MRI in addition to the lesions to be treated with RFA. More than 4 weeks must have elapsed from the time of major surgery or completion of the last dose of chemotherapy, radiation therapy, investigational therapy and patients must adequately recover from these effects. Life expectancy of >3 months. Karnofsky performance status >70%. Patients must have normal organ and marrow functions as defined below: absolute neutrophil count >1,500/mm^3 platelets >70,000/mm^3 total bilirubin <1.5 mg/dL AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal creatinine within normal institutional limits OR creatinine clearance >60mL/min/1.73 m^2 for patients with creatinine levels above institutional normal. albumin > 2.8 mg/dL Patients must have adequate clotting function (platelet > 70k; INR<1.4; PTT<60). Age >18 years. The effects of DCs on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. No history of autoimmune diseases. Ability to understand the willingness to sign a written informed consent document. Exclusion Criteria:- Patients may not be receiving anticoagulation therapy. Patients may not be receiving any other investigational agents. Patients with known brain metastases will be excluded because of their poor prognosis and because they often develop progressive neurological dysfunction that would confound the evaluation of neurological and other adverse effects. Uncontrolled concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements. Patients with a history of portal hypertension, cirrhosis/hepatitis, or with radiographic evidence of cirrhosis and/or varices are at high risk for developing a complication when undergoing a liver biopsy and may be excluded at the investigators' discretion from participation in this protocol. Patients who test positive for Hepatitis B virus, Hepatitis C virus or HIV.

Sites / Locations

  • Stanford University School of Medicine

Outcomes

Primary Outcome Measures

To determine the feasibility of harvesting autologous dendritic cells (DC) for CT-guided intratumoral DC injection
To establish the maximally tolerated dose (MTD) and dose limiting toxicity (DLT) of intratumoral autologous dendritic cell vaccination in combination with radiofrequency ablation (RFA) of liver metastases.
To determine the toxicity of this regimen

Secondary Outcome Measures

To determine the activity of this regimen as determined by tumor marker response, pathologic response and radiographic response of treated lesions.
To evaluate the immune response of patients treated with RFA + DC based on the presence and characterization of tumor infiltrating white blood cells

Full Information

First Posted
September 12, 2005
Last Updated
January 11, 2010
Sponsor
Stanford University
Collaborators
National Institutes of Health (NIH)
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1. Study Identification

Unique Protocol Identification Number
NCT00185874
Brief Title
Phase I Intratumoral Dendritic Cell Immunotherapy in Thermally Ablated Liver Metastases
Official Title
A Phase I Trial of Intratumoral Dendritic Cell Immunotherapy in Thermally Ablated Liver Metastases
Study Type
Interventional

2. Study Status

Record Verification Date
January 2010
Overall Recruitment Status
Terminated
Why Stopped
Study closed due to lack of funding
Study Start Date
January 2004 (undefined)
Primary Completion Date
October 2007 (Actual)
Study Completion Date
October 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Stanford University
Collaborators
National Institutes of Health (NIH)

4. Oversight

5. Study Description

Brief Summary
Up to twenty-two patients will be enrolled in this study to receive autologous dendritic cells (DCs) administered intratumorally into liver metastases following radiofrequency thermal ablation of those lesions. Patients will receive two vaccinations of DCs at monthly intervals. A dose escalation study of DCs will be included in this study in an attempt to define the maximum tolerated dose of administered DCs.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
22 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
Intratumoral Dendritic Cell Immunotherapy
Intervention Type
Biological
Intervention Name(s)
autologous dendritic cells
Primary Outcome Measure Information:
Title
To determine the feasibility of harvesting autologous dendritic cells (DC) for CT-guided intratumoral DC injection
Time Frame
NA- study terminated
Title
To establish the maximally tolerated dose (MTD) and dose limiting toxicity (DLT) of intratumoral autologous dendritic cell vaccination in combination with radiofrequency ablation (RFA) of liver metastases.
Time Frame
NA- study terminated
Title
To determine the toxicity of this regimen
Time Frame
NA- study terminated
Secondary Outcome Measure Information:
Title
To determine the activity of this regimen as determined by tumor marker response, pathologic response and radiographic response of treated lesions.
Time Frame
NA- study terminated
Title
To evaluate the immune response of patients treated with RFA + DC based on the presence and characterization of tumor infiltrating white blood cells
Time Frame
NA- study terminated

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:- Patients must have a histologically confirmed colorectal or neuroendocrine cancer with two or more hepatic metastatic lesions. Patients must have unresectable liver metastasis by virtue of: Bi-lobar disease. Extra-hepatic disease. Patients for whom there are medical contraindications to surgery. Anatomic sites within the liver that in the opinion of our surgeon would likely be left with positive margin. Patient must have a minimum of 2 RFA-eligible lesion in the liver. Such as hepatic lesions that are 5 cm or smaller and that are accessible to RF ablation, which in general excludes sites contiguous with critical structures such as bowel or central bile duct and also those that are not amenable to radiographic localization such as small lesions in the dome of the liver. Extra-hepatic disease will be allowed provided that the liver lesions represent the most life-threatening site for that patient. Examples include sub centimeter asymptomatic lung metastases or asymptomatic retroperitoneal lymph nodes or peritoneal metastases Evaluable disease by CT scan or MRI in addition to the lesions to be treated with RFA. More than 4 weeks must have elapsed from the time of major surgery or completion of the last dose of chemotherapy, radiation therapy, investigational therapy and patients must adequately recover from these effects. Life expectancy of >3 months. Karnofsky performance status >70%. Patients must have normal organ and marrow functions as defined below: absolute neutrophil count >1,500/mm^3 platelets >70,000/mm^3 total bilirubin <1.5 mg/dL AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal creatinine within normal institutional limits OR creatinine clearance >60mL/min/1.73 m^2 for patients with creatinine levels above institutional normal. albumin > 2.8 mg/dL Patients must have adequate clotting function (platelet > 70k; INR<1.4; PTT<60). Age >18 years. The effects of DCs on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. No history of autoimmune diseases. Ability to understand the willingness to sign a written informed consent document. Exclusion Criteria:- Patients may not be receiving anticoagulation therapy. Patients may not be receiving any other investigational agents. Patients with known brain metastases will be excluded because of their poor prognosis and because they often develop progressive neurological dysfunction that would confound the evaluation of neurological and other adverse effects. Uncontrolled concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements. Patients with a history of portal hypertension, cirrhosis/hepatitis, or with radiographic evidence of cirrhosis and/or varices are at high risk for developing a complication when undergoing a liver biopsy and may be excluded at the investigators' discretion from participation in this protocol. Patients who test positive for Hepatitis B virus, Hepatitis C virus or HIV.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Edgar G Engleman
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University School of Medicine
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States

12. IPD Sharing Statement

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Phase I Intratumoral Dendritic Cell Immunotherapy in Thermally Ablated Liver Metastases

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