Study of a DNA Immunotherapy to Treat Melanoma

A Phase I/II Trial of SCIB1, a DNA Immunotherapy, in the Treatment of Patients With Malignant Melanoma

The study is an investigation of a novel immunotherapy, SCIB1, for the treatment of melanoma. SCIB1 is a solution of plasmid DNA molecules which will express a modified antibody in human cells. The antibody modifications are designed to stimulate the patient's immune T cells to have a strong and specific reaction against melanoma cells which should then be eliminated. SCIB1 is injected into muscle using a device which simultaneously delivers an electrical impulse to enhance the transfer of SCIB1 into muscle cells. The trial will assess the safety and tolerability of SCIB1, the safety and performance of the injection device and the immunological effects of SCIB1. This is the first study of SCIB1 in humans and the trial has two parts, in the first part the dose will be escalated to determine a safe and tolerable level up to a maximum of 8 mg per dose. In the second part patients will receive the dose determined in the first part. Patients will have stage III or IV melanoma, be HLA type A2 and have a life expectancy of at least three months. All patients will receive 5 injections of SCIB1 over 5.5 months. At the discretion of the investigator, patients may continue to receive SCIB1 at 3-6 month intervals for 5 years. The study will be conducted at major cancer centres in the UK only and is expected to last for seven years. Patients will be followed up for five years after they have completed the trial.

Study Overview

• Status: Terminated
• Conditions: Malignant Melanoma
• Intervention / Treatment: Biological: SCIB1

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Leeds, United Kingdom, LS9 7TF
    • St James' Institute of Oncology
  • Manchester, United Kingdom, M20 4BX
    • Christie Hospital
  • Nottingham, United Kingdom, NG5 1PB
    • Department of Clinical Oncology, City Hospital
  • Southampton, United Kingdom, SO16 6YD
    • Department of Medical Oncology, Southampton General Hospital
  • Surrey
    • Guildford, Surrey, United Kingdom, GU2 7XX
      • Department of Medical Oncology, The Royal Surrey County Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Part One and Part Two (8.0 mg dose):

• Histologically confirmed Stage IV or Stage III malignant melanoma, as defined by the American Joint Committee on Cancer (AJCC).
• Must have measurable disease (RECIST 1.0)

Part Two (4.0 mg dose) only:

• Histologically confirmed, resected Stage III or resected Stage IV malignant melanoma, as defined by the AJCC, within 12 months of resection and with no tumour detectable at the time of screening.

Part One and Part Two:

• HLA-A2 positive.
• Positive for HLA-DR4, HLA-DR7, HLA-DR53 or HLA-DQ6.
• Lymphocyte count ≥ 5 x 10e9 cells/mL.
• Serum lactate dehydrogenase (LDH) ≤ upper limit of normal.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Willing and able to give written, informed consent.
• If male or female of childbearing potential, must be willing to use an effective contraceptive during the course of the study and for three months afterwards.

Exclusion Criteria:

• Known brain metastases at screening.
• Life expectancy of less than three months.
• Patients with TNM classification M1c at screening.
• Prior systemic anti-cancer treatment within four weeks of screening.
• Prior treatment with systemic corticosteroids or other immunosuppressants within four weeks of screening.
• Previous (within five years) or current malignancy at other sites with the exception of curatively treated local tumours such as carcinoma-in-situ of the cervix, basal or squamous cell carcinoma of the skin.
• Pregnant or lactating women.
• Presence of any uncontrolled and significant medical or psychiatric condition which would interfere with trial safety assessments. Caution should be used for patients with suspected or diagnosed epilepsy.
• Any electronic stimulation device such as cardiac demand pacemaker, automatic implantable cardiac defibrillator, nerve stimulators or deep brain stimulators.
• Individuals in which a skin-fold measurement of the cutaneous and subcutaneous tissue for all eligible injection sites (deltoid or quadriceps muscles with intact lymph drainage) exceeds 40 mm.
• Individuals with a heart rate of ≤ 50 beats per minute, history of significant cardiac abnormality and/or significant abnormal baseline electrocardiogram (ECG) readout.
• Treatment with any investigational product within the four weeks preceding screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: SCIB1

Biological: SCIB1; Aqueous solution of plasmid DNA administered by intramuscular injection using the TDS-IM electroporation device (Ichor Medical Systems, Inc.) at week 0, 3, 6, 12 and 24. Part 1 of the study will escalate through 0.4, 2.0, 4.0 and 8.0 mg dose level cohorts, each of three patients. In Part 2 of the study the 4.0 and 8.0 mg doses will be administered in the same regimen. At the discretion of the investigator, patients in both parts of the study may continue to receive SCIB1 at 3-6 month intervals for 5 years.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety & Tolerability	Recording and assessment of adverse events to establish safety and tolerability of an investigational immunotherapy, SCIB1, in patients with melanoma whose cancer has spread from the initial tumour (i.e., stage III or stage IV melanoma).	Duration of treatment phase: up to 5.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety, tolerability, biological and clinical effects	(i) Recording and assessment of adverse events and patient recorded experience to establish safety and tolerability of SCIB1 administered intramuscularly to melanoma patients using the TDS IM device. (ii) Cellular immune response by ex vivo assay induced by SCIB1 administered intramuscularly to melanoma patients using the TDS-IM device. (iii) Tumour response by CT scan in patients treated with SCIB1 (Part One only).	Duration of treatment phase: up to 5.5 years

Collaborators and Investigators

• Sponsor: Scancell Ltd
• Investigators: Study Director: Poulam M Patel, MD, Department of Clinical Oncology, City Hospital, Nottingham, UK; Principal Investigator: Paul Lorigan, MD, Department of Medical Oncology, Christie Hospital, Manchester, UK; Principal Investigator: Maria Marples, MD, St James' Institute of Oncology, Leeds, UK; Principal Investigator: Christian Ottensmeier, MD, Department of Medical Oncology, Southampton General Hospital, UK; Principal Investigator: Hardev Pandha, MD, Department of Medical Oncology, Royal Surrey County Hospital, Guildford, UK

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2010
• Primary Completion (Actual): July 7, 2017
• Study Completion (Actual): July 7, 2017

Study Registration Dates

• First Submitted: May 24, 2010
• First Submitted That Met QC Criteria: June 4, 2010
• First Posted (Estimate): June 7, 2010

Study Record Updates

• Last Update Posted (Actual): August 21, 2017
• Last Update Submitted That Met QC Criteria: August 16, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Immunotherapy; Melanoma; Gene therapy; Cancer vaccine; Electroporation; DNA plasmid; CTL response
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: SCIB1-001