Dendritic Cell Vaccination for Patients with Solid Tumors

Therapeutic Efficacy of Wilms' Tumor Gene (WT1) MRNA-electroporated Autologous Dendritic Cell Vaccination in Patients with Solid Tumors: a Phase I/feasibility Study

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.

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.