dendritic cell vaccination for patients with solid tumors

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

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.


Eligibility criteria:
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.