Alpha-type-1 Dendritic Cell-based Vaccines in Patients With Metastatic Colorectal Cancer
March 31, 2016 updated by: Pawel Kalinski
Phase I Evaluation of Semi-continuous Alpha-type-1 Dendritic Cell-based Vaccines in Patients With Metastatic Colorectal Cancer
The purpose of this study is to evaluate the administration, safety and immunologic effectiveness of an experimental vaccine for colorectal cancer patients.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
Dendritic cell (DC)-based vaccination, usually administered by a traditional intradermal route, is a new treatment option for cancer patients. While the previous DC-based vaccination trials have shown the safety of this approach and its ability to induce objective clinical responses, the overall efficacy of DC-based vaccines is still disappointing (Rosenberg et al., 2004). We hypothesize that the two likely causes of such limited clinical activity are: A) suboptimal type of DCs used as a vaccine and B) suboptimal modes of use of such vaccines that do not allow the vaccinated patients to fully benefit from DC biology.
We will conduct a pilot evaluation of the therapeutic vaccination with DC1s loaded with autologous tumor material, in patients with metastatic colorectal cancer that have been resected to no or minimal evidence of disease.The proposed evaluation of the novel intralymphatic route of DC-based vaccination will allow us to administer the vaccine in a way that is more physiologic with respect to the kinetics of antigen appearance to the lymph nodes and is feasible to be performed in repetitive fashion, without damaging local lymph nodes.
Study Type
Interventional
Enrollment (Actual)
15
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15232
- University of Cancer Institute
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
14 years to 76 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Histologically or cytologically confirmed metastatic colorectal cancer with minimal evidence of disease or resectable metastases (to include extra-hepatic metastases).
- Availability of metastatic tumor material, from hepatic metastasis and additional sites, that can be resected under sterile conditions for autologous vaccine preparation (not all tumors harvested will be of sufficient quantity or quality to make vaccine, therefore some subjects may not receive vaccine).
- No chemotherapy, radiotherapy, major surgery, or biologic therapy for their malignancy in the 4 weeks prior to the vaccine administration and must have recovered from all side effects.
- An ECOG performance standard of 0, 1 or 2.
- Adequate hepatic function as evidenced by bilirubin < 2.0 mg/dL and a PT < 2 seconds of the upper limit of normal.
- Age equal to 18 years or older and greater than 30 kg.
- Platelet counts greater than 100,000, a hematocrit > 27.0, a white blood count > 3000/µl, and a creatinine less than or equal to 1.5 mg/dL or a creatinine clearance of > 60 mL/min.
- Aware of the neoplastic nature of his/her illness, the experimental nature of the therapy, alternative treatments, potential benefits and risks, and willing to sign an informed consent.
- Patients must be able to understand and be willing to sign a written informed consent document.
Exclusion Criteria:
- Subjects currently treated with systemic immunosuppressive agents, including steroids, are ineligible until 4 weeks after removal from immunosuppressive treatment. Subjects on maintenance steroids because of adrenal insufficiency are eligible.
- Subjects with severely abnormal liver function tests [AST (SGOT), ALT (SGPT), GGT, Alk.Phos, LDH, and total bilirubin greater than 2 X ULN]
- Subjects with uncontrolled pain.
- Subjects with active autoimmune disease, positive serology for HIV, HBV, or HCV (testing will be performed with FDA licensed blood donor tests).
- Subjects with concurrent additional malignancy (with exception of non-melanoma skin cancers and carcinoma in situ of the cervix).
- Subjects who are allergic to or develop an allergy to heparin.
- Subjects who are pregnant.
- Subjects who have sensitivity to drugs that provide local anesthesia.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Active Comparator: Intradermal administration
|
Each patient will receive four courses of vaccination with 2 million tumor-loaded DCs at week 0, 4, 8, and 12.
A course consists of 4 intradermal injections once a day for 4 days.
Each patient will receive four courses of vaccination with 2 million tumor-loaded DCs at week 0, 4, 8, and 12.
A course consists of 1 intranodal injection.
Each patient will receive four courses of vaccination with 2 million tumor-loaded DCs at week 0, 4, 8, and 12.
A course consists of a 4-day intralymphatic infusion.
|
|
Active Comparator: Intranodal administration
|
Each patient will receive four courses of vaccination with 2 million tumor-loaded DCs at week 0, 4, 8, and 12.
A course consists of 4 intradermal injections once a day for 4 days.
Each patient will receive four courses of vaccination with 2 million tumor-loaded DCs at week 0, 4, 8, and 12.
A course consists of 1 intranodal injection.
Each patient will receive four courses of vaccination with 2 million tumor-loaded DCs at week 0, 4, 8, and 12.
A course consists of a 4-day intralymphatic infusion.
|
|
Active Comparator: Intralymphatic infusion
|
Each patient will receive four courses of vaccination with 2 million tumor-loaded DCs at week 0, 4, 8, and 12.
A course consists of 4 intradermal injections once a day for 4 days.
Each patient will receive four courses of vaccination with 2 million tumor-loaded DCs at week 0, 4, 8, and 12.
A course consists of 1 intranodal injection.
Each patient will receive four courses of vaccination with 2 million tumor-loaded DCs at week 0, 4, 8, and 12.
A course consists of a 4-day intralymphatic infusion.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
The primary endpoint of this study is to evaluate the feasibility and safety of semi-continuous intralymphatic vaccination dendritic cells.
Time Frame: 4 to 14 weeks
|
4 to 14 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
The secondary objective of this study is to evaluate the immunity results from either single injections or semi-continuous infusion, intradermal or intranodal, administered immunization with the DC vaccine for colorectal cancer (CRC) patients.
Time Frame: 4 to 14 weeks
|
4 to 14 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: David L. Bartlett, MD, University of Pittsburgh
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
January 1, 2008
Primary Completion (Actual)
December 1, 2011
Study Completion (Actual)
April 1, 2014
Study Registration Dates
First Submitted
November 13, 2007
First Submitted That Met QC Criteria
November 13, 2007
First Posted (Estimate)
November 14, 2007
Study Record Updates
Last Update Posted (Estimate)
April 1, 2016
Last Update Submitted That Met QC Criteria
March 31, 2016
Last Verified
March 1, 2016
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 05-063
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