Alpha-type-1 Dendritic Cell-based Vaccines in Patients With Metastatic Colorectal Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Pawel Kalinski, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00558051
First received: November 13, 2007
Last updated: October 14, 2013
Last verified: October 2013
  Purpose

The purpose of this study is to evaluate the administration, safety and immunologic effectiveness of an experimental vaccine for colorectal cancer patients.


Condition Intervention Phase
Metastatic Colorectal Cancer
Biological: DC-based vaccine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Phase I Evaluation of Semi-continuous Alpha-type-1 Dendritic Cell-based Vaccines in Patients With Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 9
Study Start Date: January 2008
Estimated Study Completion Date: July 2014
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Intradermal administration
Intradermal administration
Biological: DC-based vaccine
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.
Active Comparator: Intranodal administration
Intranodal administration
Biological: DC-based vaccine
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.
Active Comparator: Intralymphatic infusion
Intralymphatic infusion
Biological: DC-based vaccine
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00558051

Locations
United States, Pennsylvania
University of Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
Pawel Kalinski
Investigators
Principal Investigator: David L. Bartlett, MD University of Pittsburgh
  More Information

No publications provided

Responsible Party: Pawel Kalinski, Professor of Surgery, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00558051     History of Changes
Other Study ID Numbers: 05-063
Study First Received: November 13, 2007
Last Updated: October 14, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Pittsburgh:
colorectal
cancer
vaccine
isolated hepatic metastases

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases

ClinicalTrials.gov processed this record on August 27, 2014