Melanoma
Conditions
Keywords
melanoma, lipoplexes, plasmid, herpes simplex thymidine kinase, interleukin-2, granulocyte-macrophage colony-stimulating factor, tumor vaccine, suicide gene
Brief summary
Safety evaluation of combined immunogene therapy in patients with advanced melanoma.
Detailed description
This phase I clinical protocol is proposed to evaluate the safety of combined immunotherapy genetics in humans. This treatment combines the high local cytotoxicity of the suicide gene system (HSV thymidine kinase: HSVt k) / prodrug (ganciclovir: GCV) with the immunostimulation of interleukin2 (hIL2) and immunoamplification of granulocyte and macrophage colony stimulating factor (hGMCSF) in the presence of tumor antigens. The proposed scheme consists in the periodic intra / peritumoral application of plasmid DNA complexes: cationic lipid (lipoplexes) containing the HSVtk gene, co-administered with the prodrug GCV, and subcutaneous injections of a vaccine (LGvax) produced with formolized extracts of allogeneic melanoma combined with lipoplexes carrying the hIL2 and hGMCSF genes.
Interventions
BIOLOGICALSuicide plus immunogene therapy
1. Intra and peritumoral infiltrates with multiple injections of 0.1 ml/cm2 or 0.2 ml/cm3 of lipoplexes bearing the HSVtk suicide gene (1: 1; 1 mg/ml, according to tumor size), co-administered with GCV (12.5 mg/ml). Patients start with a minimum of 0.5 ml and at the 3rd week, the maximum dose is scaled according to the tumor size up to 2 ml maximum. 2. Treated simultaneously with a subcutaneous vaccine produced with: * Formolized allogeneic tumor extracts and, * Lipoplexes carrying hIL-2 and hGM-CSF genes (0.5 mg each).
Sponsors
Instituto de Oncología Ángel H. Roffo
National Agency for Scientific and Technological Promotion, Argentina
National Council of Scientific and Technical Research, Argentina
University of Buenos Aires
Hospital Italiano de Buenos Aires
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Suicide plus immunogene therapy
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with histologically and / or cytologically confirmed melanoma. * Patients progressed or are intolerant to conventional systemic treatments. * Patients that are not candidates for surgery under oncologic criteria (complete resection). * Performance status (ECOG) 0 or 1. * Patients with life expectancy greater than 6 months. * Patients with at least one accessible target lesion for gene inoculation (superficial localizations of the primary tumor, satelitosis, subcutaneous or accessible lymph node metastasis). * Patients with measurable disease (according to RECIST 1.1 criteria, irrespective of the target lesion chosen for suicide gene inoculation) * Patients with signed informed consent.
Exclusion criteria
* Patients with uncontrolled cardiovascular disease * Patients with uncontrolled respiratory disease. * Patients with uncontrolled immune disease. * Patients with glucocorticoids or immunosuppressive drugs or agents with immunomodulatory activity (except non-steroidal anti-inflammatory agents) up to 2 weeks before treatment. * Patients performing other experimental therapies. * Patients who are pregnant or breastfeeding. * Patients undergoing concurrent chemotherapy or radiation therapy. * Uncontrolled diabetes. * Patients with active diagnosis of other malignant neoplasms. * HIV-positive patients. * Uncontrolled thyroid abnormality. * Patients with significant medical morbidity. * Patients with a history of allergic reactions to chemicals or similar to those used in this study. * Metastasis in the central nervous system. * Laboratory eligibility criteria excluded: * Hemoglobin: \<8 g / dL, leukocytes: \<3,000 / mm3, platelets: \<100,000 / mm3, neutrophils: \<1000 / mm3, hematocrit: \<25%. bilirubin\> 2.0 mg / dL, GOT or GPT: 2.5 times\> than normal upper institutional limit (ULN), alkaline phosphatase: 2 times\> ULN, creatinine\> 2.0 mg / dL, creatinine clearence : \<60 ml / min / 1.73 m2.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety reported as the number of treatment-related adverse events as assessed by CTCAE v4.03 | 1 year | Number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 (https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE\_4.03\_2010-06-14\_QuickReference\_5x7.pdf). |
Countries
Argentina
Outcome results
None listed