Dendritic Cell Vaccination for Patients with Solid Tumors

Phase 1

Completed

• Conditions: Renal Cell Carcinoma; Malignant Mesothelioma; Sarcomas; Breast Cancers; Glioblastoma; Colorectal Tumors

• Registration Number: NCT01291420
• Lead Sponsor: University Hospital, Antwerp

Brief Summary

The aim of this study is to evaluate the immunogenicity and clinical efficacy of intradermal vaccination with autologous RNA-modified dendritic cells (DCs) - engineered to express the WT1 protein - in patients with limited spread metastatic solid tumors, i.e. breast cancers, glioblastoma grade IV, sarcomas, malignant mesothelioma and colorectal tumors. Based on the results of our previously performed phase I study with autologous WT1 mRNA-transfected DC, the investigators hypothesize that the vaccination with DC will be well-tolerated and will result in an increase in WT1-specific CD8+ T cell responses.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-05-03
• Study First Submitted: 2011-02-07
• Study First Submitted QC: 2011-02-07
• Study First Posted: 2011-02-08
• Primary Completion: 2016-04-25
• Study Completion: 2017-11-02
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-04
• Last Update Posted: 2024-12-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

1. Tumor type:

   Metastatic or Locally Advanced Breast Cancer; Malignant Mesothelioma; Glioblastoma Multiforme (Grade IV); Sarcoma's; Colorectal tumors or rare tumors (less than 500 patients a year)

2. Extent of disease:

   • Metastatic Breast Cancer or High Risk Locally Advanced Breast Cancer

     • Partial or Complete response after first line chemotherapy for both metastatic or locally advanced breast cancer. Minimal metastatic disease under hormonal treatment

     • High risk Locally Advanced breast cancer defined as (and/or):

       • Age < 60 years old
       • ER, PR and Her-2 Neu negative tumors
       • > 4 lymphnodes at initial presentation
       • Mastitis Carcinomatosis
       • Pregnancy associated Breast Cancer

   • Malignant Mesothelioma:

     • Partial or Complete response after first line chemotherapy not amendable for surgery
     • Adjuvant after debulking surgery

   • Glioblastoma Multiforme

     • In Recurrent Disease after optimal treatment according to Stupp regimen
     • In primary disease after debulking surgery, Temodal/radiotherapy and Temodal chemotherapy for 6 months

   • Sarcoma's

     • After adjuvant chemotherapy for uterine sarcoma's
     • After Optimal or Debulking Surgery for liposarcoma's, synovial cell sarcoma's
     • Recurrent sarcoma's with limited disease

   • Colorectal tumors

     • K-ras wild-type tumors with inoperable lymphnode metastasis after standard chemotherapy (FOLFOX, FOLFIRI)

3. Patient Characteristics

   • Prior treatments: Patients must have received at least one prior chemotherapeutic regimen and must be more than 1 month past the last treatment.
   • Age: ≥ 18 years old
   • Performance status: WHO PS grade 0-1 (Appendix B)
   • Objectively assessable parameters of life expectancy: more than 3 months
   • Prior and concomitant associated diseases allowed with the exception of underlying autoimmune disease and positive serology for HIV/HBV/HCV
   • No concomitant use of immunosuppressive drugs, hormonal treatment for breast cancer is allowed in case of stable disease
   • Adequate renal and liver function, i.e. creatinin and bilirubin = 1.2 times the upper limit of normal
   • Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
   • Women of child-bearing potential should use adequate contraception prior to study entry and for the duration of study participation

Exclusion Criteria

1. Subjects with concurrent additional malignancy (with exception of non-melanoma skin cancers and carcinoma in situ of the cervix)
2. Subjects who are pregnant
3. Subjects who have sensitivity to drugs that provide local anesthesia
4. Subjects needing corticosteroids 1 mg/kg during vaccination; corticosteroids are allowed as part of their treatment when taken ≥ 30 days before the start of vaccination.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Immunogenicity of intradermal DC vaccination	up to 2 months	Immunogenicity of intradermal DC vaccination (cellular + humoral immunity against WT1 antigen) as measured by: 1. In vivo cytokine response (serum concentration of cytokines); 2. In vivo anti-WT1 antibody responses; 3. In vitro T cell reactivity towards MHC class I and II-restricted WT1 epitopes by multiplex-cytokine assay using peripheral blood and DTH-infiltrating T cells; 4. Delayed type hypersensitivity (DTH) responses; 5. Quantitative and qualitative FACS analysis of WT1-specific-positive CD8+ T cells using HLA-A2 WT1 multimers

Trial Locations

Locations (1)

Antwerp University Hospital, Center for Cellular Therapy and Regenerative Medicine; 🇧🇪 Edegem, Antwerp, Belgium