REO13 Melanoma With of Without GM-CSF

NCT03282188 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: MO15/121
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Open-label, non-randomised, single centre study which will assess the presence of reovirus (Reolysin®), following intravenous administration with or without Granulocyte-macrophage colony-stimulating factor (GM-CSF) given to patients prior to surgery for metastatic melanoma. All patients will receive an initial low 'immunisation' dose of intravenous reovirus. Patients will be enrolled sequentially in to each of the two cohorts receiving either reovirus alone, or reovirus plus GM-CSF. For this study we anticipate 8-16 evaluable patients, up to 8 for each group. The endpoints of this study will compare the 2 treatment groups for reovirus tumour infiltration and replication. Compare the neutralising antibody development and cell-mediated immune response and identify any adverse events and laboratory toxicities.

Conditions

Melanoma; Cancer of Skin

Outcome Measures

Primary Outcomes (1)

• Comparison between treatment groups of reovirus tumour infiltration by immunohistochemistry (IHC)

  Through study completion, an average of 18 months

Secondary Outcomes (3)

• Comparison between treatment groups of reovirus tumour replication, as assessed by qRT-PCR

  Through study completion, an average of 18 months

• Comparison between treatment groups of neutralising antibody development development and cell-mediated immune response

  Through study completion, an average of 18 months

• Comparison between treatment groups of cell-mediated immune response

  Through study completion, an average of 18 months

Study Arms (2)

GROUP A (Reovirus only)

EXPERIMENTAL

Group A patients will receive an initial low 'immunisation' dose of intravenous reovirus (1x108 TCID50), to ensure that neutralising antibody (NAB) levels have risen by the time a full cycle of reovirus is given. Group A patients will then receive only 1 cycle of treatment which will comprise of reovirus only at 1x1010 TCID50 as a 1-hour IV infusion on 2 consecutive days.

Biological: Reolysin

GROUP B (Reovirus plus GM-CSF)

EXPERIMENTAL

Group B patients will receive an initial low 'immunisation' dose of intravenous reovirus (1x108 TCID50), to ensure that neutralising antibody (NAB) levels have risen by the time a full cycle of reovirus plus GM-CSF is given. Group B patients will be given a subcutaneous injection of GM-CSF (50mcg/day) for 3 days, followed by only 1 cycle of treatment which will comprise of reovirus at 1x1010 TCID50 as a 1-hour IV infusion on 2 consecutive days

Biological: Reolysin; Drug: GM-CSF

Interventions

Reolysin BIOLOGICAL

Reolysin® is a proprietary isolate of Reovirus Type 3 Dearing, a non-enveloped human reovirus with a genome that consists of 10 segments of double-stranded RNA. The human reovirus possesses an innate ability to replicate specifically in transformed cells possessing an activated Ras signalling pathway, a situation often found in malignant cells. Reovirus has been shown to reach and target melanoma cancer cells.

GROUP A (Reovirus only); GROUP B (Reovirus plus GM-CSF)

GM-CSF DRUG

GM-CSF is a recombinant human granulocyte-macrophage colony stimulating factor (rhu GM-CSF) produced by recombinant DNA technology in a yeast (S. cerevisiae) expression system. GM-CSF is a hematopoietic growth factor which stimulates proliferation and differentiation of hematopoietic progenitor cells. GM-CSF is a key cytokine in the differentiation of dendritic cells. It has been used as an immune adjuvant in therapeutic vaccines in pre-clinical and clinical studies, administered as cytokine released from gene-transduced tumour or stromal cells or as recombinant protein. At low doses GM-CSF may enhance migration and differentiation of dendritic cells to local antigen presentation, and is a potent adjuvant to generate specific systemic anti-tumour efficacy.

Also known as: LEUKINE, Sargramostim

GROUP B (Reovirus plus GM-CSF)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be male or female subjects with histologically diagnosed melanoma.
• Be at least 18 years of age.
• Be appropriate for resection of advanced melanoma (Stage 3/4). Patients may or may not have more widespread metastatic disease.
• Have completed any previous systemic chemotherapy, radiotherapy or surgery (except biopsies) at least 28 days before entry into the study.
• Have NO continuing acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedures, i.e., all such effects must have resolved to Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0) Grade ≤1.
• Have an ECOG Performance Score of 0 or 1.
• Have a life expectancy of at least 3 months.
• Have baseline laboratory results at the time of consent as follows:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109 \[SI units 109/L\]
• Platelets ≥ 100 x109 \[SI units 109/L\] (without platelet transfusion)
• Haemoglobin ≥ 9.0 g/dL \[SI units gm/L\] (with or without RBC transfusion)
• Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
• Bilirubin ≤ 1.5 x ULN
• AST/ALT ≤ 2.5 x ULN
• Negative serum pregnancy test for females of childbearing potential.

You may not qualify if:

• Be on concurrent therapy with any other investigational anticancer agent while on study.
• Be on immunosuppressive therapy other than steroids.
• Have known HIV infection or hepatitis B or C.
• Be pregnant or breast feeding. Female patients must agree to use effective contraception, be surgically sterile, or be postmenopausal. Male patients must agree to use effective contraception or be surgically sterile.
• Have clinically significant cardiac disease (New York Heart Association, Class III or IV) including clinically significant arrhythmia, uncontrolled angina pectoris, or myocardial infarction within 1 year prior to study entry.
• Have dementia or altered mental status that would prohibit informed consent.
• Have any other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the Principal

Sponsors & Collaborators

• University of Leeds: lead
• Yorkshire Cancer Research: collaborator

MeSH Terms

Conditions

Melanoma; Skin Neoplasms

Interventions

reolysin; Granulocyte-Macrophage Colony-Stimulating Factor; sargramostim

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor and Medical Oncology Consultant

Model Details: This is a open-label, non-randomised, single centre study.

Study Record Dates

• First Submitted: August 30, 2017
• First Posted: September 13, 2017
• Study Start: October 1, 2017
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2018
• Last Updated: May 4, 2018

Record last verified: 2018-05