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

NCT ID: NCT00558051

Last Updated: 2016-04-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2014-04-30

Brief Summary

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

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.

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Intradermal administration

Intradermal administration

Group Type: ACTIVE_COMPARATOR

DC-based vaccine

Intervention Type: BIOLOGICAL

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.

Intranodal administration

Intranodal administration

Group Type: ACTIVE_COMPARATOR

DC-based vaccine

Intervention Type: BIOLOGICAL

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.

Intralymphatic infusion

Intralymphatic infusion

Group Type: ACTIVE_COMPARATOR

DC-based vaccine

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: BIOLOGICAL

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pawel Kalinski

OTHER

Sponsor Role: lead

Responsible Party

Pawel Kalinski

Professor of Surgery

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

David L. Bartlett, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

University of Cancer Institute

Pittsburgh, Pennsylvania, United States

Countries

United States

References

Radomski M, Zeh HJ, Edington HD, Pingpank JF, Butterfield LH, Whiteside TL, Wieckowski E, Bartlett DL, Kalinski P. Prolonged intralymphatic delivery of dendritic cells through implantable lymphatic ports in patients with advanced cancer. J Immunother Cancer. 2016 Apr 19;4:24. doi: 10.1186/s40425-016-0128-y. eCollection 2016.

Reference Type: DERIVED

PMID: 27096100 (View on PubMed)

Other Identifiers

05-063

Identifier Type: -

Identifier Source: org_study_id