Treatment of skin cancer using a different approach than surgery using an electroporation device that makes the tumour absorb more drug while leaving the healthy tissue alone combined with an immune modulator that enhances the anti-tumour immune response.
- Conditions
- Advanced Melanoma CancerTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-004420-22-IE
- Lead Sponsor
- niversity College Cork
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 10
1.Histologically verified melanoma.
2.Patient must have a node/cutaneous lesion which is amenable to ECT.
3.Patient must have at least one measurable lesion on a CT scan as defined by Modified RECIST.
4. Unresectable, locally advanced, or metastatic melanoma with disease progression and no curable options with the standard of care.
5.Men or women aged at least 18 years.
6.Life expectancy of at least 3 months.
7.Performance status (ECOG < or equal to 2).
8.Treatment free interval of at least 2 weeks after previously applied therapy.
9.WBC greater than or equal to 4.4 x 10 ^9/L, ANC great than or equal to 1.4x 10^9/L
10.Platelets greater than or equal to 140 x 10^9/L
11.Hemoglobin greater than or equal to 9g/dL
12.Serum creatinine less than or equal to 1.5 times the upper limit of normal or creatinine clearance greater than or equal to 40 mls/min (using the Cockcroft-Gault Equation)
13.AST and ALT less than or equal to 3 times ULN or less than or equal to 5 times ULN for subjects with liver metastasis
14.Total bilirubin: less than or equal to 3 x ULN, [except subjects with Gilbert’s Syndrome, who must have a total bilirubin less than 3.0 mg/dL]
15.Patients must not have any physical, social or psychological condition that in the opinion of the investigator would impair the patients ability to provide informed consent.
16.a) A female of Non-Childbearing potential (i.e. physiologically incapable of becoming pregnant) is eligible to participate in the study if she:
- has had a hysterectomy
- has had a bilateral oophorectomy (ovariectomy)
- has had a bilateral tubal ligation
- Is post-menopausal:
[Post Menopausal definition: Patients not using hormone replacement therapy (HRT) must have experienced total cessation of menses for = 1 year and be greater than 45 years in age, OR, in questionable cases, have a follicle stimulating hormone (FSH) value >40 mIU/mL and an oestradiol value < 40pg/mL (<140 pmol/L).
Patients using HRT must have experienced total cessation of menses for > or = 1 year and be greater than 45 years of age OR have had documented evidence of menopause based on FSH and oestradiol concentrations prior to initiation of HRT.]
b) A female of Childbearing potential is eligible to participate in the study only if she has had a negative serum or urine pregnancy test within 2 weeks prior to the first dose of study treatment, preferably as close to the first dose as possible.
c) Women of Childbearing potential and Men must agree to use adequate contraception since signing of the informed consent form until at least 6 months after the last study drug administration. The investigator or a designated associate is requested to advise the patient how to achieve an adequate birth control.
18. Subjects with brain metastasis are eligible if these have been treated and there is no MRI (MRI -except where contraindicated in which case CT Scan is acceptable) evidence of progression for at least 8 weeks after treatment is complete and within 28 days prior or the first dose of study drug administration. There must be no requirement for immunosupressive doses of systemic corticosteroids (>10mg/day prednisolone equivalents) for at least 2 weeks prior to study drug administration.
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 8
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2
1.Coagulation disorder
2.Patients with a clinically manifested arrhythmia or with a pacemaker
3.Patients with epilepsy.
4.Pregnancy or lactation/breastfeeding.
5.History of or current active autoimmune diseases, [e.g. including but not limited to inflammatory bowel diseases [IBD], rheumatoid arthritis, autoimmune thyroiditis, autoimmune hepatitis, systemic sclerosis (scleroderma and variants), systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies (such as Guillain-Barre syndrome). Vitiligo and adequately controlled endocrine deficiencies such as hypothyroidism are not exclusionary.]
6.No known active infectious disease including including HIV, HBV and HCV.
7.Patients who have had a history of acute diverticulitis, intra-abdominal abscess, GI obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation.
8.History of or current immunodeficiency disease [e.g. splenectomy or splenic irradiation];
9.Prior allogeneic stem cell transplantation;
10.Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea.
11.Concomitant therapy [e.g.: anti-cancer agent, potent immunosuppressive agents, surgery or radiotherapy or other investigational anti-cancer therapies or chronic use of systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses) with the exception of low dose steroids for AE management as deemed clinically appropriate.
12.Prior therapies with systemic immunosuppressive agents [within prior 2 years (excluding episodic low dose corticosteroids, eg, for treatment of allergic dermatologic conditions); prior therapies with cytotoxic or investigational drugs within 2 weeks of randomization;]
13.Prior immunotherapy within the previous 4 weeks.
14.Treatment with any other investigational products/chemotherapy/RT, etc. within 2 weeks prior to inclusion into this study.
15.Participation in another clinical study.
16.Patients with any other clinical condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with the study requirements.
17.Contraindications for bleomycin use including acute pulmonary infection and severe pulmonary disease.
18.Contraindication for bleomycin use: allergic reactions to bleomycin observed in previous treatment.
19.Contraindication for bleomycin use: if cumulative dose of 250mg BLM/m2 was previously exceeded.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The Primary objective of this study is an assessment of the tolerability and safety of ipilimumab delivered systemically with electrochemotherapy delivered locally to the tumour.;Secondary Objective: The Secondary objectives of this study are to investigate change to the total systemic tumour volume and structure as measured and evaluated radiologically: 12, and 24 weeks post the start of the procedure.<br>;Primary end point(s): Primary end point : Continuous assessment of safety by reviewing adverse events as they arise. The investigation will be put on hold if unacceptable safety issues are outstanding.;Timepoint(s) of evaluation of this end point: Continuous assessment of AEs and SAEs as they occur <br><br>Safety End points: <br>- Evaluation of any adverse events reported.<br>- Evaluation of any severe adverse events reported.<br>- Evaluation of the safety profile of treatment<br>
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Continuous assessment of safety by reviewing adverse events as they arise. The investigation will be put on hold if unacceptable safety issues are outstanding.<br><br>- Evaluation of tumour regression / reduction in volume;Timepoint(s) of evaluation of this end point: Measured via CT or MRI scan at 12, or 24 weeks post the initial procedure.