Clinical trial NCT01983748: Dendritic Cells Plus Autologous Tumor RNA in Uveal Melanoma
Official title: A NON-COMMERCIAL, MULTICENTER, RANDOMIZED, TWO-ARMED, OPEN-LABEL PHASE III STUDY TO EVALUATE THE ADJUVANT VACCINATION WITH TUMOR RNA-LOADED AUTOLOGOUS DENDRITIC CELLS VERSUS OBSERVATION OF PATIENTS WITH RESECTED MONOSOMY 3 UVEAL MELANOMA
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Uveal Melanoma
Keywords: Uveal Melanoma, Monosomy 3
Lead sponsor: University Hospital Erlangen
Sponsor class: OTHER
Collaborators: name: University Hospital Lübeck
name: University Hospital Munich
name: Universitätsklinikum Hamburg-Eppendorf
name: University Hospital Homburg/Saar
name: Universitätsklinikum Köln
name: University Hospital Tuebingen
name: University Hospital, Essen
name: Wuerzburg University Hospital
First posted: 2013-11-14
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Patients suffering from uveal melanoma (typed positive for monosomy 3 and without evidence for metastases) will be vaccinated over a period of 2 years with Dendritic Cell loaded with autologous Tumor RNA.

200 patients will be included. The Trial is an open multicenter Phase III Trial.

Detailed description: Trial arm A (DCaT-RNA) = Experimental intervention: Patients in arm A receive 8 vaccinations over a period of 2 years consisting of autologous, mature, monocyte-derived Dendritic Cells loaded with autologous tumor RNA (20 mio DC per vaccination); cells are given via intravenous infusions; vaccinations are followed by a 1 year observation (staging every 3 months)

Trial arm B (Observation) = Control: Patients in arm B receive standard care (observation only with staging every 3 months)

Eligibility criteria: Inclusion Criteria:

* Patients must suffer from melanoma of the uvea (stage T2, T3 and T4 \[AJCC TNM grading 2009\]).
* Uveal melanoma must be resected and display a monosomy for chromosome 3 (will be determined by a validated qualitative analysis of loss of heterozygosity). Tumor material has to be stored appropriately in RNAlater solution for RNA preparation.
* The patient has to be free of detectable tumor at the time point of study enrollment (adjuvant setting), as assessed by clinical inspection, abdominal sonography, chest X-ray and evaluation of the tumor-marker S-100..
* Patients must have a WHO performance status of 0, 1 or 2 and must be in stable medical condition.
* Patients must be between 18 and 75 years old and must be able and willing to give informed consent.
* Women of child-bearing age must have a negative pregnancy test, and must oblige to use effective contraception until at least 4 weeks after the last vaccination.
* Patients must be willing to get hospitalized for at least 4 hours following vaccination(s), and to cooperate for the whole period of the trial.
* Patients must have fully recovered from surgery.
* Signed informed consent

Exclusion Criteria:

* Any other major serious illness \[e.g. active systemic infections, immunodeficiency disease, clinically significant heart disease, respiratory disease, bleeding disorders, cancer etc.\] or a contraindication to leukapheresis.
* Evidence for HIV-1, HIV -2, HTLV-1, HBV, or HCV infection.
* Active autoimmune disease (such as but not limited to Lupus erythematosus, autoimmune thyroiditis or uveitis, multiple sclerosis, inflammatory bowel disease). Vitiligo and pathological laboratory results (autoantibodies) without clinical symptoms are, however, not an exclusion criterion.
* Previous splenectomy or radiation therapy to the spleen.
* Patients with organ allografts.
* Concomitant treatment with chemotherapy, immunotherapy, any investigational drug and paramedical substances. Patients may receive concomitant medications to control symptoms such as analgetics, antihypertensive medication, etc.
* History of other active malignant neoplasm within the preceding 5 years (excluding non-melanoma skin cancer or carcinoma in situ of the cervix).
* Organic brain syndrome or significant psychiatric abnormality which would impede informed consent and / or AND preclude participation in the full protocol and follow up.
* Positive pregnancy test / Pregnancy or lactation. If pregnancy occurs during the course of the trial to female patients in arm A or B, the patient has to be excluded.
* Detection of metastases. If uveal melanoma metastases appear during the course of the trial, the patient has to be excluded.
* Lack of compliance of the patient.

Primary outcomes:
measure: Prolongation of Overall survival
timeFrame: Assessment every 3 months
Secondary outcomes:
measure: Prolongation of disease free survival
timeFrame: Assessment every 3 months
Other outcomes:
measure: Assessment for induction of immune responses
timeFrame: The induction of immune responses will be researched in selected patients (in a minimum of 15 survivors per trial arm) 2 years after randomization.
Locations:
city: Erlangen
country: Germany
facility: Dept. of Dermatology, University Hospital
state: Bayern
city: Erlangen
country: Germany
facility: University Hospital Department of Ophtalmology
state: Bayern
city: Würzburg
country: Germany
facility: University Hospital Department of Ophtalmology
state: Bayern
city: Dessau
country: Germany
facility: Städtisches Klinikum
city: Essen
country: Germany
facility: University Hospital Department of Ophtalmology
city: Homburg/Saar
country: Germany
facility: University Hospital Department of Ophtalmology
city: Lübeck
country: Germany
facility: University Hospital Department of Ophtalmology
city: Tübingen
country: Germany
facility: University Hospital Department of Ophtalmology
Study officials:
affiliation: University Hospital Erlangen
name: Beatrice Schuler-Thurner, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schuler-Thurner B, Bartz-Schmidt KU, Bornfeld N, Cursiefen C, Fuisting B, Grisanti S, Heindl LM, Holbach L, Keseru M, Knorr H, Koch K, Kruse F, Meiller R, Metz C, Meyer-ter-Vehn T, Much M, Reinsberg M, Schliep S, Seitz B, Schuler G, Susskind D, Viestenz A, Wagenfeld L, Zeschnigk M. [Immunotherapy of uveal melanoma: vaccination against cancer. Multicenter adjuvant phase 3 vaccination study using dendritic cells laden with tumor RNA for large newly diagnosed uveal melanoma]. Ophthalmologe. 2015 Dec;112(12):1017-21. doi: 10.1007/s00347-015-0162-z. German.