Randomized phase II clinical trial on mRNA electroporated autologous dendritic cells for stage III/IV melanoma in patients who are free from measurable tumor lesions following the local treatment of macro metastases

Phase 1

• Conditions: stage III/IV melanoma in patients who are free from measurable tumor lesions following the local treatment of macro metastases; MedDRA version: 13.1Level: PTClassification code 10025671Term: Malignant melanoma stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 13.1Level: PTClassification code 10025670Term: Malignant melanoma stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-001410-33-BE
• Lead Sponsor: Z BRUSSE

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-05-09
• Last Update Posted: 21 July 2016

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 88

Inclusion Criteria

1.Able and willing to give valid written informed consent before undergoing any study-related activities; patients must be willing to cooperate for the whole period of the study, and accept to be treated according to the study protocol regardless of the study arm the patient is allocated to following the randomization step;
2.Histological documentation of AJCC stage III (Tx, N1b,-2b,-2c or -3, M0), or stage IV melanoma;
3.Primary melanoma of the skin, unknown primary; patients with primary mucosal, or uveal melanoma (melanoma originating in the choroid, iris or ciliar body) are not eligible;
4.At baseline tumor assessment by whole-body FDG-PET/CT, patients should be free from measurable tumor lesions (measurability is defined according to RECIST (v1.1)), and free from symptomatic non-measurable tumor lesions (e.g. bone metastasis, or pleural effusion);
5.Prior local treatment of primary and metastatic tumor lesions is allowed (e.g. surgical resection, isolated limb perfusion, radiofrequency ablation, radiotherapy, cryotherapy, …). Treated tumor lesions should be free from progression at baseline assessment;
6.Normal organ function and normal hematological parameters (as reflected by blood values); baseline laboratory parameters should be within normal range, except for the following laboratory parameters, which must be within the ranges specified:
BLOOD PARAMETERRANGE
HEMOGLOBIN= 10 G/DL
GRANULOCYTES= 1,500/µL
LYMPHOCYTES= 500/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 that allows to undergo leukapheresis;
9.No prior systemic therapy for melanoma;
10.Full recovery from all prior therapies. A minimal 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 (see Appendix D);
12.Male and female patients = 18 years of age;
13.No need for uninterrupted therapeutic anticoagulation (e.g. for recent thrombo-embolism, or cardiac valve prosthesis)
14.No prior history of a serious autoimmune disorder
15.No concomitant medication with immune suppressive drugs (e.g. oral corticosteroids).
16.Women of childbearing potential (WOCBP) 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. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal [defined as amenorrhea = 12 consecutive months; or women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level > 35mIU/mL]. Even women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where pa

Exclusion Criteria

1.Evidence of immunodeficiency. Autoimmune disease requiring medical treatment (e.g. corticosteroids or other immunosuppressive drugs). Vitiligo (skin depigmentation) 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. Subjects with 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 ? 5 years following the diagnosis are eligible for this study;
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 human chorionic gonadotropin [?-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, such as hormonal contraception, intra-uterine pessar, condoms or sterilization, 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified