Clinical trial NCT03338777: Suicide Plus Immune Gene Therapy for Advanced Melanoma
Official title: Phase 1 Suicide Plus Immune Gene Therapy for Advanced Melanoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: EARLY_PHASE1
Conditions: Melanoma
Keywords: melanoma
lipoplexes
plasmid
herpes simplex thymidine kinase
interleukin-2
granulocyte-macrophage colony-stimulating factor
tumor vaccine
suicide gene
Lead sponsor: Hospital Italiano de Buenos Aires
Sponsor class: OTHER
Collaborators: name: Instituto de Oncología Ángel H. Roffo
name: National Agency for Scientific and Technological Promotion, Argentina
name: National Council of Scientific and Technical Research, Argentina
name: University of Buenos Aires
First posted: 2017-11-09
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Suicide plus immunogene therapy
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety reported as the number of treatment-related adverse events as assessed by CTCAE v4.03
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Hospital Italiano
state: Buenos Aires
Study officials:
affiliation: Hospital Italiano
name: Ventura Simonovich, MD
role: PRINCIPAL_INVESTIGATOR
References: