Safety and Efficacy of Intramuscular Electrotransfer of Plasmid AMEP in Patients Suffering From Advanced or Metastatic Melanoma (AIMM)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
BioAlliance Pharma SA
ClinicalTrials.gov Identifier:
NCT01764009
First received: January 7, 2013
Last updated: NA
Last verified: January 2013
History: No changes posted
  Purpose

The objective of the present trial is:

  • 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.
  • to determine the local and general safety of intramuscular electrotransferred Plasmid AMEP
  • to evaluate the efficacy of intramuscular electrotransferred Plasmid AMEP

Condition Intervention Phase
Melanoma
Biological: naked DNA coding for protein AMEP
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Intramuscular Electrotransfer of Plasmid AMEP in Patients Suffering From Advanced or Metastatic Melanoma: an Open-label Phase I/II Clinical Trial - The AIMM Study (AMEP In Metastatic Melanoma)

Resource links provided by NLM:


Further study details as provided by BioAlliance Pharma SA:

Primary Outcome Measures:
  • Safety-Dose Limiting toxicity determination [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
    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


Secondary Outcome Measures:
  • Safety- determination of the repeated dose [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
    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.


Other Outcome Measures:
  • tolerability [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
    • Local tolerability of the intramuscular electrotransfer of Plasmid AMEP
    • Overall tolerability: incidence, nature and severity of adverse events and serious adverse events


Estimated Enrollment: 36
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Plasmid AMEP electrotransfer in muscle Biological: naked DNA coding for protein AMEP
injections 28days interval of 3 increasing doses of plasmid with electrotransfer
Other Names:
  • electrotransfer
  • electroporation

Detailed Description:

In this open-label, multicentre, dose escalation phase I study, successive cohorts of 3 patients suffering from advanced or metastatic melanoma will be electrotransferred increasing doses of Plasmid AMEP into muscle. Treatment will be repeated every 28 days until progression or limiting toxicity.

Consecutive cohorts of 3 to 6 patients will be treated with increasing doses of Plasmid AMEP at three dose levels: 0.25 mg, 1 mg and 4 mg according to an adapted 3+3 design. There will be no intra-patient dose escalation.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Aged over 18 years
  • Patient with histologically or cytologically confirmed melanoma
  • Patient with unresectable advanced or metastatic (stage III or IV) melanoma
  • Patient with progressive melanoma (any BRAF status is permitted) not responding or intolerant to previous treatments, including patients with asymptomatic and not rapidly progressive brain metastases.
  • Patient with a minimum of one measurable lesion according to RECIST guideline 1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
  • Patient having given a written informed consent

Exclusion Criteria:

  • Patient eligible for curative treatments and/or any palliative treatments with demonstrated efficacy, including current treatments for brain metastasis, and including available BRAF inhibitors as indicated for patients carrying B-RAF mutated tumours if applicable.
  • Patient with history of any other cancer within five years before enrollment (except cured basal cell carcinoma or cervical cancer in situ)
  • Patient with inadequate organ function, defined as:
  • Platelet count < 75.103 /L (> grade 2 NCI CTCAE)
  • Absolute neutrophil count < 1.109 /L (> grade 2)
  • Hemoglobin < 9 g/dL
  • INR increased or prolonged activated partial thromboplastin time (aPTT) upper the limit of normal (ULN) (≥ grade 1)
  • Creatinine clearance < 60 mL/min (Cockcroft and Gault formula) (≥ grade 2)
  • Patient with ALT > 3 ULN (≥ grade 2) or patient with symptomatic liver metastasis with ALT > 5 ULN (> grade 2)
  • Serum Total Bilirubin > 1.5 ULN (≥ grade 2); Patient with Gilbert's syndrome could be included if hyperbilirubinemia ≤ 3 ULN
  • Not medically controlled coagulation disorder (i.e hemophilia, protein C or S deficiency…)
  • Patient with electronic pacemakers, defibrillators, or any implanted electronic device
  • Any cardiac dysrhythmia (> grade 2) (i.e significant ventricular arrhythmia as persistent ventricular tachycardia and/or ventricular fibrillation; severe conduction disorders as atrio-ventricular block 2 and 3, sino-atrial block)
  • Recent (less than 6 months) acute vascular diseases (i.e stroke, myocardial infarction)
  • Arterial vascular disorders ≥ grade 2
  • Serious, non-healed wound, ulcer or bone fracture
  • Significant traumatic injury within 28 days prior to study treatment start or anticipation of the need for major surgery during study treatment
  • Evidence of ongoing or active viral or bacterial infection ( i.e bacterial infection requiring IV antibiotics)
  • Patient with life expectancy less than 3 months
  • Prior systemic therapy or any other antineoplastic treatments within the last 4 weeks, including radiotherapy or surgery
  • Patients who had participated in another clinical trial in the last 30 days prior to enrolment in the present clinical trial
  • 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 (i.e oral contraception or intra-uterine device for woman; i.e condom for man)
  • Pregnant or nursing women
  • Any significant disease, including psychiatric and neuromuscular disease, which may affect the proper evaluation of safety or efficacy or may affect ability to give informed consent
  • Patients unwilling or unable to comply with protocol requirements and scheduled visits
  • For contrast enhanced ultrasound (CEUS): known contraindications to SonoVue as described in the summary product characteristics (i.e cardiac or pulmonary history, hypersensitivity to sulphur hexafluoride or to any of the components of SonoVue)
  • For the part II: prophylactic phenytoin in combination with dacarbazine.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01764009

Locations
France
Gustave Roussy Institute,
Kremlin Bicetre, France, 94805
Hôpital Saint Louis. Service de dermatologie
Paris, France, 75010
CHU Nancy Hôpital Brabois
Vandoeuvre Les Nancy, France, 54511
Slovenia
Institute of Oncology Ljubljana
Ljubljana, Slovenia, SI-1000
Sponsors and Collaborators
BioAlliance Pharma SA
Investigators
Study Director: Bérangère VASSEUR, M.D. BioAlliance Pharma
  More Information

No publications provided

Responsible Party: BioAlliance Pharma SA
ClinicalTrials.gov Identifier: NCT01764009     History of Changes
Other Study ID Numbers: BA2011/15/02, 2011-005538-20
Study First Received: January 7, 2013
Last Updated: January 7, 2013
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
Slovenia: Agency for Medicinal Products - Ministry of Health
Italy: The Italian Medicines Agency

Keywords provided by BioAlliance Pharma SA:
Advanced Melanoma
Metastatic Melanoma
Melanoma Stage III and IV

Additional relevant MeSH terms:
Melanoma
Stress, Psychological
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Behavioral Symptoms

ClinicalTrials.gov processed this record on April 17, 2014