Dendritic Cells Plus Autologous Tumor RNA in Uveal Melanoma

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Uveal Melanoma
• Intervention / Treatment: Biological: Autologous Dendritic Cells loaded with autologous Tumor RNA

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)

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Dessau, Germany, 06847
    • Städtisches Klinikum
  • Essen, Germany, 45122
    • University Hospital Department of Ophtalmology
  • Homburg/Saar, Germany, 66421
    • University Hospital Department of Ophtalmology
  • Lübeck, Germany, 23538
    • University Hospital Department of Ophtalmology
  • Tübingen, Germany, 72076
    • University Hospital Department of Ophtalmology
  • Bayern
    • Erlangen, Bayern, Germany, 90154
      • Dept. of Dermatology, University Hospital
    • Erlangen, Bayern, Germany, 91054
      • University Hospital Department of Ophtalmology
    • Würzburg, Bayern, Germany, 97080
      • University Hospital Department of Ophtalmology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; Biological/Vaccine; Autologous Dendritic Cells loaded with autologous Tumor RNA	Biological: Autologous Dendritic Cells loaded with autologous Tumor RNA
No Intervention: B; Control, Standard of care, which is clinical control every 3 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prolongation of Overall survival	Clinical staging every 3 months from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months, followed by telephone interviews.	Assessment every 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prolongation of disease free survival	Skin, lymph node and ophtalmological inspection , medical history, laboratory, and abdominal sonography will be performed every 3 months, chest x ray will be performed every 6 months	Assessment every 3 months

Other Outcome Measures

Outcome Measure	Time Frame
Assessment for induction of immune responses	The induction of immune responses will be researched in selected patients (in a minimum of 15 survivors per trial arm) 2 years after randomization.

Collaborators and Investigators

• Sponsor: University Hospital Erlangen
• Collaborators: University Hospital, Essen; University Hospital Tuebingen; Universitätsklinikum Hamburg-Eppendorf; Wuerzburg University Hospital; University Hospital Munich; Universitätsklinikum Köln; University Hospital Lübeck; University Hospital Homburg/Saar
• Investigators: Principal Investigator: Beatrice Schuler-Thurner, MD, University Hospital Erlangen

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: September 17, 2013
• First Submitted That Met QC Criteria: November 7, 2013
• First Posted (Estimate): November 14, 2013

Study Record Updates

• Last Update Posted (Actual): December 2, 2022
• Last Update Submitted That Met QC Criteria: November 29, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Uveal Melanoma, Monosomy 3
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Eye Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Uveal Diseases; Neuroendocrine Tumors; Nevi and Melanomas; Eye Neoplasms; Melanoma; Uveal Neoplasms
• Other Study ID Numbers: DERMA-ER-DC 08