REO13 Melanoma With of Without GM-CSF

May 1, 2018 updated by: Christy Ralph, University of Leeds

A Clinical Study to Evaluate the Biological Effects of Intravenous Wild-type Reovirus (Reolysin®), With of Without GM-CSF, in Advanced Melanoma

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is an open-label, non-randomised, single centre study of intravenous reovirus (Reolysin®) with or without Granulocyte-macrophage colony-stimulating factor (GM-CSF) given to patients prior to surgery for metastatic melanoma. Patients will be eligible if undergoing surgery for local control of lymph node involvement (with or without stage 4 metastases) or if planned for resection of cutaneous, subcutaneous, musculoskeletal or visceral metastases for local control, palliation of symptoms or personal choice.

All 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 +/- GM-CSF is given. All patients will receive only 1 cycle of treatment which will comprise: i) For reovirus alone patients (Group A), 1x1010 TCID50 as a 1-hour IV infusion on 2 consecutive days; ii) For reovirus plus GM-CSF patients (Group B), subcutaneous GM-CSF (50mcg/day) for 3 days, followed by 2 days of reovirus. Both doses of reovirus will be at 1x1010 TCID50.

Patients will be enrolled sequentially into each of the two cohorts receiving intravenous reovirus alone, or reovirus plus GM-CSF. The addition of GM-CSF is designed to address effects on the translational objectives/endpoints of this study, rather than primary toxicity, although all patients will be monitored for safety. Clinical assessment will be performed at screening (within 14 days of start of treatment), at day 1 (1st GM-CSF dose/none), day 8 and at the final study visit (40 days (+/- 14 days) post treatment with reovirus). Safety bloods will be taken at screening, at treatment (Day 1), before each dose of reovirus (Day 4 & 5), at Day 8 and at the final study visit (Day 40). Immunological assays, including reovirus antibody levels, will be performed before low-dose reovirus priming (Day -10 to -6), pre-treatment on Day 1, on Day 4 and 5 (pre-reovirus infusion and 60 minutes post-infusion), Day 8, and at the final study visit (Day 40). Patients with accessible skin or subcutaneous metastases will be asked for an optional additional pre-treatment biopsy which will be taken before low-dose reovirus priming.

All procedures will be performed as an outpatient or day case, apart from surgery in melanoma patients requiring admission as part of standard clinical care. Imaging will be as for standard clinical care only. Following surgical resection the tumour will be assessed for viral status and anti-tumour effects by e.g. standard histology, immunohistochemistry, RT-PCR and electron microscopy. Further imaging and follow-up beyond the final study visit (Day 40 +/- 14 days) will be as for standard clinical care only.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Be male or female subjects with histologically diagnosed melanoma.
  2. Be at least 18 years of age.
  3. Be appropriate for resection of advanced melanoma (Stage 3/4). Patients may or may not have more widespread metastatic disease.
  4. Have completed any previous systemic chemotherapy, radiotherapy or surgery (except biopsies) at least 28 days before entry into the study.
  5. 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.
  6. Have an ECOG Performance Score of 0 or 1.
  7. Have a life expectancy of at least 3 months.

  8. Have baseline laboratory results at the time of consent as follows:

    1. Absolute neutrophil count (ANC) ≥ 1.5 x 109 [SI units 109/L]
    2. Platelets ≥ 100 x109 [SI units 109/L] (without platelet transfusion)
    3. Haemoglobin ≥ 9.0 g/dL [SI units gm/L] (with or without RBC transfusion)
    4. Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
    5. Bilirubin ≤ 1.5 x ULN
    6. AST/ALT ≤ 2.5 x ULN
    7. Negative serum pregnancy test for females of childbearing potential.
  9. Have signed informed consent.
  10. Be willing and able to comply with scheduled visits, the treatment plan, and laboratory tests

Exclusion Criteria:

  1. Be on concurrent therapy with any other investigational anticancer agent while on study.
  2. Be on immunosuppressive therapy other than steroids.
  3. Have known HIV infection or hepatitis B or C.
  4. 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.
  5. 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.
  6. Have dementia or altered mental status that would prohibit informed consent.
  7. 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: GROUP A (Reovirus only)
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
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.
Experimental: GROUP B (Reovirus plus GM-CSF)
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
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.
Drug: GM-CSF
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.
Other Names:
  • Sargramostim
  • LEUKINE

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Comparison between treatment groups of reovirus tumour infiltration by immunohistochemistry (IHC)
Time Frame: Through study completion, an average of 18 months
Through study completion, an average of 18 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Comparison between treatment groups of reovirus tumour replication, as assessed by qRT-PCR
Time Frame: Through study completion, an average of 18 months
Through study completion, an average of 18 months
Comparison between treatment groups of neutralising antibody development development and cell-mediated immune response
Time Frame: Through study completion, an average of 18 months
Through study completion, an average of 18 months
Comparison between treatment groups of cell-mediated immune response
Time Frame: Through study completion, an average of 18 months
Through study completion, an average of 18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Leeds

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Yorkshire Cancer Research

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2017

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2018

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 30, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 11, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 13, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 4, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 1, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MO15/121

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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