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

Primary Purpose

Metastatic Colorectal Cancer

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

DC-based vaccine

About this trial

This is an interventional basic science trial for Metastatic Colorectal Cancer focused on measuring Colorectal Cancer, Colorectal Carcinoma, Colorectal Tumors, Neoplasms, Colorectal

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University of Cancer Institute

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Arm Label

Intradermal administration

Intranodal administration

Intralymphatic infusion

Arm Description

Intradermal administration

Intranodal administration

Intralymphatic infusion

Outcomes

Primary Outcome Measures

The primary endpoint of this study is to evaluate the feasibility and safety of semi-continuous intralymphatic vaccination dendritic cells.

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.

Full Information

NCT ID

NCT00558051

First Posted

November 13, 2007

Last Updated

March 31, 2016

Sponsor

Pawel Kalinski

1. Study Identification

Unique Protocol Identification Number

NCT00558051

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2016

Overall Recruitment Status

Completed

Study Start Date

January 2008 (undefined)

Primary Completion Date

December 2011 (Actual)

Study Completion Date

April 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Pawel Kalinski

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastatic Colorectal Cancer

Keywords

Colorectal Cancer, Colorectal Carcinoma, Colorectal Tumors, Neoplasms, Colorectal

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

15 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Intradermal administration

Arm Type

Active Comparator

Arm Description

Intradermal administration

Arm Title

Intranodal administration

Arm Type

Active Comparator

Arm Description

Intranodal administration

Arm Title

Intralymphatic infusion

Arm Type

Active Comparator

Arm Description

Intralymphatic infusion

Intervention Type

Biological

Intervention Name(s)

DC-based vaccine

Intervention Description

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

Intervention Name(s)

DC-based vaccine

Intervention Description

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

Intervention Name(s)

DC-based vaccine

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Secondary Outcome Measure Information:

Title

Time Frame

4 to 14 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David L. Bartlett, MD

Organizational Affiliation

University of Pittsburgh

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Cancer Institute

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15232

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

27096100

Citation

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.

Results Reference

derived

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

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