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Randomized Controlled Phase II Clinical Trial on mRNA Electroporated Autologous Dendritic Cells for Stage III/IV Melanoma Patients Who Are Disease-free Following the Local Treatment of Macrometastases


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Malignant Melanoma Stage III, Malignant Melanoma Stage IV

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Trial Information

Randomized Controlled Phase II Clinical Trial on mRNA Electroporated Autologous Dendritic Cells for Stage III/IV Melanoma Patients Who Are Disease-free Following the Local Treatment of Macrometastases


This is an open label, 2-arm, 1-stage, randomized controlled phase II study in patients with
AJCC stage IIIB/C & -IV melanoma. At baseline tumor assessment (using total body
FDG-PET/CT), patients should be free from measurable tumor lesions (according to RECISTv1.1
definitions) following prior local therapy (e.g. following surgical resection, isolated limb
perfusion, radiofrequency ablation, cryotherapy, radiotherapy, electrochemotherapy, …).
Patients should not have symptomatic non-measurable tumor lesions (e.g. bone metastasis, or
pleural effusion), and lesions treated by prior local therapy should be free from
progression. Patients should not have received any prior systemic therapy (non-experimental
or experimental).

- Patients will be randomized between two treatment arms (Arm-A and -B). In study Arm-A,
patients will receive DC-administrations during one year following randomization.
Salvage treatment by local therapies will be allowed during the study treatment in
Arm-A. In study Arm-B, patients will initiate DC-administrations only after documented
recurrence of the melanoma that cannot be salvaged by local therapy.

- The primary endpoint of this clinical trial is to determine the rate (%) of patients
who are free from macrometastases (: measurable tumor lesions and symptomatic
non-measurable tumor lesions) at 1-year (= 52 weeks) after randomization.

Patients treated on Arm-B will serve as a contemporary control-arm to help interpreting the
outcome of patients treated in Arm-A. By design (phase II) this trial will not be powered to
statistically prove a predefined difference between the two study arms (this would require a
phase III design). Patients treated in Arm-B will be able to initiate immunotherapy with
autologous DC at the time of recurrence that can not be salvaged by local therapy.
Documentation of the anti-tumor activity and survival following DC-treatment at recurrence
in Arm-B patients will be a secondary objective of this clinical trial.


Inclusion Criteria:



1. Able and willing to give written informed consent

2. Histological documentation of AJCC stage III or stage IV melanoma

3. melanoma (melanoma originating in the choroid, iris or ciliar body are not eligible)

4. baseline tumor assessment by whole-body FDG-PET/CT, patients should be free from
measurable tumor lesions (RECIST (v1.1)), and free from symptomatic non-measurable
tumor lesions

5. Prior local treatment of primary and metastatic tumor lesions is allowed . Treated
tumor lesions should be free from progression at baseline assessment

6. Normal organ function and normal hematological parameters;laboratory parameters
should be within normal range, except following laboratory parameters:HEMOGLOBIN ≥ 10
G/DL; GRANULOCYTES ≥ 1,500/µL; LYMPHOCYTES ≥ 1000/µL; PLATELETS ≥ 100,000/µL; SERUM
CREATININ ≤ 2.0 MG/DL; SERUM BILIRUBIN ≤ 2.0 MG/DL; AST AND ALT ≤ 2 X THE NORMAL
UPPER LIMITS; LDH ≤ 1,5X NORMAL UPPER LIMIT; CRP ≤ 1,5X NORMAL UPPER LIMIT;
PROTHROMBIN TIME (PT) INTERNATIONAL NORMALIZED RATIO (INR) AND PARTIAL THROMBOPLASTIN
TIME (PTT) WITHIN NORMAL LIMITS

7. Negative serology for HCV, and HIV; absence of active infection with HBV, and
Syphilis; If positive results for HepB or Syphilis indicate immunity and are not
indicative of active infection, the patient can enter the study.

8. Adequate venous access(to undergo leukapheresis)

9. No prior systemic therapy for melanoma

10. Full recovery from all prior therapies. A period of 4 weeks following major surgery,
radiation therapy, or ILP, or any other major invasive procedure is required

11. Baseline WHO performance status of 0 or 1

12. Male and female patients ≥ 18 years

13. No need for uninterrupted therapeutic anticoagulation

14. No prior history of a serious autoimmune disorder

15. No concomitant medication with immune suppressive drugs

16. Women of childbearing potential must be using an adequate method of contraception to
avoid pregnancy throughout the study and for up to 8 weeks after the study in such a
manner that the risk of pregnancy is minimized.

Exclusion Criteria:

1. Evidence of immunodeficiency or autoimmune disease requiring medical treatment (e.g.
corticosteroids or other immunosuppressive drugs).Vitiligo is not an exclusion
criterion

2. Any serious acute or chronic illnesses (e.g. heart disease NYHA Class III or
IV,renal-,liver- or pulmonary insufficiency) or other conditions requiring concurrent
medications not allowed during this study (e.g. active chronic infections requiring
antibiotics)

3. History of malignancy. Curatively treated cervical carcinoma in situ,or squamous-,or
basal cell carcinoma of the skin, or subjects who have been treated and
recurrence-free of other malignancies for more than 5 years following the diagnosis
are eligible

4. Inability to undergo FDG-PET/CT, or MRI examination

5. Mental impairment that may compromise the ability to give informed consent and comply
with the requirements of the study

6. Participation in any other clinical trial involving another investigational agent
within 4 weeks prior to enrollment

7. Subject is pregnant (positive serum beta-HCG test at screening) or is currently
breast-feeding, anticipates becoming pregnant/impregnating their partner during the
study or within 6 months after study participation, or subject does not agree to
follow acceptable methods of birth control, to avoid conception during the study and
for at least 6 months after receiving the last dose of study treatment

8. Current alcohol dependence or drug abuse

9. Known hypersensitivity to the study treatment

10. Legal incapacity or limited legal capacity

11. Presence of any psychological, familial, sociological, or geographical condition
potentially hampering compliance with the study protocol and follow-up schedule.

12. Signs and symptoms suggestive of transmissible spongiform encephalopathy,or family
members who suffer(ed) from such.

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

1-year disease free survival percentage

Outcome Description:

Patients will be evaluated 52 weeks following randomization for their melanoma disease status (= macro-metastases present or absent)

Outcome Time Frame:

1-year following recruitment date

Safety Issue:

No

Principal Investigator

Bart Neyns, Phd Md

Investigator Role:

Principal Investigator

Investigator Affiliation:

UZ Brussel

Authority:

Belgium: Federal Agency for Medicinal Products and Health Products

Study ID:

DC-MEL

NCT ID:

NCT01676779

Start Date:

October 2012

Completion Date:

September 2016

Related Keywords:

  • Malignant Melanoma Stage III
  • Malignant Melanoma Stage IV
  • melanoma
  • no evidence of disease
  • resection
  • macro-metastases
  • Melanoma

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