E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Therapeutic vaccination with dendritic cells loaded with Wilms' tumor 1 protein in patients with solid tumors |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065252 |
E.1.2 | Term | Solid tumor |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10046859 |
E.1.2 | Term | Vaccination |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective 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. glioblastoma grade IV, renal cell carcinoma, sarcomas, breast cancers. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objective of this study is to evaluate if the level of WT1 RNA in the peripheral blood (Cilloni 2002; Cilloni 2008), could also serve as an informative marker to evaluate the effect of a WT1-targeted cancer vaccine. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion 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:
a. Metastatic Breast Cancer or High Risk Locally Advanced Breast Cancer
i. Partial or Complete response after first line chemotherapy for both metastatic or locally advanced breast cancer. Minimal metastatic disease under hormonal treatment
ii. High risk Locally Advanced breast cancer defined as (and/or):
1. Age < 60 years
2. ER, PR and Her-2 Neu negative tumors
3. > 4 lymphnodes at initial presentation
4. Mastitis Carcinomatosis
5. Pregnancy associated Breast Cancer
b. Malignant Mesothelioma:
i. Partial or Complete response after first line chemotherapy not amendable for surgery
ii. Adjuvant after debulking surgery
c. Glioblastoma Multiforme
i. In Recurrent Disease after optimal treatment according to Stupp regimen
ii. In primary disease after debulking surgery, Temodal/radiotherapy and Temodal chemotherapy for 6 months
d. Sarcoma’s
i. After adjuvant chemotherapy for uterine sarcoma’s
ii. After Optimal or Debulking Surgery for liposarcoma’s, synovialcell sarcoma’s
iii. Recurrent sarcoma’s with limited disease
e. Colorectal tumors
i. K-ras wild-type tumors with inoperable lymphnode metastasis after standard chemotherapy (FOLFOX, FOLFIRI)
3. Patient Characteristics
a. Prior treatments: Patients must have received at least one prior chemotherapeutic regimen and must be more than 1 month past the last treatment.
b. Age: ≥ 18 years
c. Performance status: WHO PS grade 0-1 (Appendix B)
d. Objectively assessable parameters of life expectancy: more than 3 months
e. Prior and concomitant associated diseases allowed with the exception of underlying autoimmune disease and positive serology for HIV/HBV/HCV
f. No concomitant use of immunosuppressive drugs, hormonal treatment for breast cancer is allowed in case of stable disease
g. Adequate renal and liver function, i.e. creatinin and bilirubin = 1.2 times the upper limit of normal
h. 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
i. Women of child-bearing potential should use adequate contraception prior to study entry and for the duration of study participation
|
|
E.4 | Principal exclusion criteria |
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.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Safety and feasibility
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. For more details on the immune-monitoring analysis, see section 7.
4. Delayed type hypersensitivity (DTH) responses to intradermally injected DC alone; DC + sig-WT1-DClamp mRNA + KLH (= vaccine); DC+ sig-WT1-DClamp mRNA; KLH (positive control) and PBS (negative control)
5. Quantitative and qualitative FACS analysis of WT1-specific-positive CD8+ T cells using HLA-A2 WT1 multimers (only for HLA-A2+ patients).
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
|
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
last visit of last subject |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |