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

Metastatic Colorectal Cancer Clinical Trial

Official title:

Phase I Evaluation of Semi-continuous Alpha-type-1 Dendritic Cell-based Vaccines in Patients With Metastatic Colorectal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00558051
• Other study ID #: 05-063
• Status: Completed
• Phase: Phase 1
• First received: November 13, 2007
• Last updated: March 31, 2016
• Start date: January 2008
• Est. completion date: April 2014

Study information

• Verified date: March 2016
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Data and Safety Monitoring BoardUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: April 2014
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	University of Cancer Institute	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Pawel Kalinski

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary endpoint of this study is to evaluate the feasibility and safety of semi-continuous intralymphatic vaccination dendritic cells.		4 to 14 weeks	Yes
Secondary	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.		4 to 14 weeks	No