Phase I Intratumoral Dendritic Cell Immunotherapy in Thermally Ablated Liver Metastases

Liver Cancer Clinical Trial

Official title:

A Phase I Trial of Intratumoral Dendritic Cell Immunotherapy in Thermally Ablated Liver Metastases

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00185874
• Other study ID #: HEP0002
• Secondary ID: HEP0002NIH 16766
• Status: Terminated
• Phase: Phase 1
• First received: September 12, 2005
• Last updated: January 11, 2010
• Start date: January 2004
• Est. completion date: October 2007

Study information

• Verified date: January 2010
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 22
• Est. completion date: October 2007
• Est. primary completion date: October 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Liver Cancer

Intervention

Biological:
• Intratumoral Dendritic Cell Immunotherapy

• autologous dendritic cells

Locations

Country	Name	City	State
United States	Stanford University School of Medicine	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Stanford University	National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the feasibility of harvesting autologous dendritic cells (DC) for CT-guided intratumoral DC injection		NA- study terminated	No
Primary	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.		NA- study terminated	No
Primary	To determine the toxicity of this regimen		NA- study terminated	Yes
Secondary	To determine the activity of this regimen as determined by tumor marker response, pathologic response and radiographic response of treated lesions.		NA- study terminated	No
Secondary	To evaluate the immune response of patients treated with RFA + DC based on the presence and characterization of tumor infiltrating white blood cells		NA- study terminated	No