Treatment of patients suffering from advanced or metastatic melanoma (stages III, IV) MedDRA version: 14.1 Level: PT Classification code 10025671 Term: Malignant melanoma stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 14.1 Level: PT Classification code 10027480 Term: Metastatic malignant melanoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 14.1 Le
Conditions
Interventions
Product Name: Plasmid AMEP
Product Code: BA015
Pharmaceutical Form: Lyophilisate for solution for injection
Current Sponsor code: BA015
Other descriptive name: Plasmid AMEP
Concentration unit: mg mill
Sponsors
BioAlliance Pharma
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged over 18 years 2. Patient with histologically or cytologically confirmed melanoma 3. Patient with unresectable advanced or metastatic (stage III or IV) melanoma 4. Patient with progressive melanoma not responding or intolerant to previous treatments; including patients with asymptomatic and not rapidly progressive brain metastases 5. Patient with a minimum of one measurable lesion according to RECIST guideline 1.1 6. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 7. Patient having given a written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 6
Exclusion criteria
Exclusion criteria: 1.Patient eligible for curative treatments and/or any palliative treatments with demonstrated efficacy, including current treatments for brain metastasis if applicable 2.Patient with history of any other cancer within five years before enrollment (except cured basal cell carcinoma or cervical cancer in situ) 3.Patient with inadequate organ function 4.Not medically controlled coagulation disorder 5.Patient with electronic pacemakers, defibrillators, or any implanted electronic device 6.Any cardiac dysrhythmia (> grade 2) 7.Recent (less than 6 months) acute vascular diseases 8.Arterial vascular disorders = grade 2 9.Serious, non-healed wound, ulcer or bone fracture 10.Significant traumatic injury within 28 days prior to study treatment start or anticipation of the need for major surgery during study treatment 11.Evidence of ongoing or active viral or bacterial infection 12.Patient with life expectancy less than 3 months 13.Prior systemic therapy or any other antineoplastic treatments within the last 4 weeks, including radiotherapy or surgery 14.Patients who had participated in another clinical trial in the last 30 days prior to enrolment in the present clinical trial 15.Man and woman of child-bearing age without effective contraception method during the study and for 3 months after the last administration of Plasmid AMEP
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1: Phase I Patients with advanced or metastatic melanoma will receive intramuscularly increasing doses of plasmid AMEP Primary objective: - To determine the dose limiting toxicity (DLT), maximal tolerated dose (MTD) and recommended phase 2 dose (RP2D) of intramuscular electrotransferred Plasmid AMEP in patients with advanced or metastatic melanoma. Part 2: Extension Phase I/II Patients with advanced or metastatic melanoma will receive intramuscularly the recommended dose of plasmid AMEP either alone or in combination with dacarbazine Primary objective: - To confirm the safety and tolerability of intramuscular electrotransferred Plasmid AMEP at the established recommended dose, alone or in combination. ;Secondary Objective: - To determine the local and general safety of intramuscular electrotransferred Plasmid AMEP - To evaluate the efficacy of intramuscular electrotransferred Plasmid AMEP alone and in combination with dacarbazine - To determine the pharmacokinetic parameters of Plasmid AMEP and dacarbazine and to evaluate the systemic exposure to AMEP protein alone and in combination with dacarbazine - To identify pharmacodynamic parameters and predictive factors of safety and/or efficacy of Plasmid AMEP alone or with combination with dacarbazine ;Primary end point(s): Phase I Primary endpoint: Dose Limiting Toxicity (DLT) defined as any grade 4 clinical or biological event related to the study treatment and occurring during the first and second course (8 weeks) Safety parameters will be assessed according to the NCI-CTCAE v4.0 classification. Phase II Primary endpoint: Overall tolerability: incidence, nature and severity of AEs and SAEs at each visit at the Plasmid AMEP recommended dose when used alone or in combination with dacarbazine. The safety parameters will be assessed according to the NCI-CTCAE v4.0 classification.;Timepoint(s) of evaluation of this end point: Safety will be evaluated at each visit during study treatment period a | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase I Secondary endpoints: Main secondary endpoints will be safety parameters; the evaluation of efficacy parameters will allow identifying preliminary efficacy of Plasmid AMEP alone and determining the RP2D. Phase II Secondary endpoints: Main secondary endpoints will be efficacy parameters of Plasmid AMEP alone or in combination with dacarbazine and safety parameters of Plasmid AMEP in combination with dacarbazine. The benefit/risk may be preliminary determined. Pharmacokinetics: - Measurements of plasma and urine Plasmid AMEP concentrations - Measurements of plasma AMEP protein concentrations - Measurements of plasma dacarbazine and main metabolites when administered alone and in combination with Plasmid AMEP. Pharmacodynamic parameters and predictive factors of safety and efficacy - Tumor expression of avß3 and a5ß1 integrins on tumor biopsies before treatment - Plasma concentrations of biomarkers including VEGF, cadherines and other relevant biomarkers prior to, during and after treatment - Effects on tumour vascularisation prior to, during and after treatment based on imaging as dynamic contrast enhanced ultrasound (CEUS) and on tumour histopathology - Pharmacogenetic analysis on tumor biopsy and blood: DNA analysis, studying gene amplification, deletion, mutation or polymorphism focused on genes involved in invasion, migration and angiogenesis pathways and directly or indirectly related to the mechanism of action of AMEP ( if appropriate genetic informed consent signed) - Correlation between plasma levels of Plasmid AMEP and AMEP protein and angiogenesis biomarkers, integrin expression, pharmacogenetic analysis and safety and efficacy parameters, if applicable. ;Timepoint(s) of evaluation of this end point: - Safety will be evaluated at each visit during study treatment period and then every 2 weeks for 2 months after last course (+/- 2 days) - Efficacy will be evaluated every 2 months (CT scan) | — |
Countries
Slovenia
Contacts
Public ContactClinical Director
BioAlliance Pharma
Outcome results
None listed