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RATIO: Rational Approach To Immuno-Oncology (RATIO)

Primary Purpose

Metastatic Melanoma

Status

Unknown status

Phase

Not Applicable

Locations

Canada

Study Type

Interventional

Intervention

Molecular Microscope Diagnostic system

About this trial

This is an interventional basic science trial for Metastatic Melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Men and women, > 18 years of age
Histologically confirmed locally advanced or metastatic melanoma with cutaneous or subcutaneous lesions
Immunotherapy treatment naïve subjects (ie, no prior systemic anticancer therapy for unresectable or metastatic melanoma)
Scheduled to receive ipilimumab, nivolumab, or combination treatment
Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2
Not pregnant or lactating. Women who are of child-bearing potential must agree to use an effective means of birth control (i.e., latex condom, diaphragm, cervical cap, etc) to avoid pregnancy.
Informed consent for microarray analysis of locally advanced lesion or skin metastasis retrieved by standard of care biopsy

Exclusion Criteria:

Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co- stimulation or immune checkpoint pathways
Subjects with active, known, or suspected autoimmune disease
If considered high-risk and tested for hepatitis: Any positive test result for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
Any significant medical condition, laboratory abnormality, or psychiatric illness, that would prevent the subject from participating in the study, places the subject at unacceptable risk if he/she were to participate in the study, or any condition that confounds the ability to interpret data from the study

Sites / Locations

Cross Cancer InstituteRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Cutaneous Biopsy for microarray analysis

Arm Description

To determine whether outcomes improve as a function of anti-tumor immunity which may enable the use of this technique as a predictive biomarker of treatment response.

Outcomes

Primary Outcome Measures

Correlation of the MMDx from pretreatment biopsy with overall response rate (ORR).

Secondary Outcome Measures

Progression Free Survival (PFS)

Overall Survival (OS)

Full Information

NCT ID

NCT02700971

First Posted

February 29, 2016

Last Updated

December 17, 2018

Sponsor

AHS Cancer Control Alberta

Collaborators

Transplant Genomics, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT02700971

Brief Title

RATIO: Rational Approach To Immuno-Oncology

Acronym

RATIO

Official Title

Rational Approach To Immuno-Oncology Microarray Prediction of Response to Nivolumab, Ipilimumab, or Combined Therapy in Subjects With Previously Untreated, Locally Advanced or Metastatic Melanoma

Study Type

Interventional

2. Study Status

Record Verification Date

December 2018

Overall Recruitment Status

Unknown status

Study Start Date

June 23, 2016 (Actual)

Primary Completion Date

December 2021 (Anticipated)

Study Completion Date

December 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AHS Cancer Control Alberta

Collaborators

Transplant Genomics, Inc.

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

This trial will utilize a Molecular MicroscopeTM diagnostic system (MMDxTM) that combines the molecular and histopathological features of biopsies, plus clinical and laboratory parameters, to create the first Integrated Diagnostic System. This MMDxTM will be utilized to phenotype cutaneous melanoma biopsy samples to detect an immune responsive mRNA signature.

Detailed Description

The trial treatment will consist of a pretreatment 18 gauge core biopsy of locally advanced or metastatic cutaneous or subcutaneous lesions. The biopsies will be stabilized on site in RNAlater and shipped to ATAGC by courier at ambient temperature. RNA will be extracted using Trizol-chloroform method and purified using RNAEasy micro kit (Qiagen). RNA samples passing the quality control test (Agilent Bioanalyzer) will be labeled, hybridized to PrimeView Affymetrix microarrays and scanned according to the manufacturer's protocol. Resulting ".CEL" files will be used for the analysis of the global gene expression. Pathogenesis Based Transcript (PBT) sets that represent molecular signatures of inflammation will be assessed in core biopsies from melanoma patients. Each PBT set gets a "score" - a summarized expression of all members of a set. PBT scores allow an estimate of pre and post-treatment immunological activity in each tumor e.g. TCMR activity or macrophage burden. PBT scores will be correlated with clinical outcome to determine the utility of this technology as a prognostic and predictive biomarker. Finally a molecular classifier predicting the response to therapy will be built.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastatic Melanoma

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

35 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Cutaneous Biopsy for microarray analysis

Arm Type

Experimental

Arm Description

To determine whether outcomes improve as a function of anti-tumor immunity which may enable the use of this technique as a predictive biomarker of treatment response.

Intervention Type

Procedure

Intervention Name(s)

Molecular Microscope Diagnostic system

Intervention Description

Consented patients with locally advanced or metastatic melanoma with This trial will utilize a Molecular MicroscopeTM diagnostic system (MMDxTM) that combines the molecular and histopathological features of biopsies, plus clinical and laboratory parameters, to create the first Integrated Diagnostic System. This MMDxTM will be utilized to phenotype cutaneous melanoma biopsy samples to detect an immune responsive mRNA signature.

Primary Outcome Measure Information:

Title

Correlation of the MMDx from pretreatment biopsy with overall response rate (ORR).

Time Frame

24 months

Secondary Outcome Measure Information:

Title

Progression Free Survival (PFS)

Time Frame

24 months

Title

Overall Survival (OS)

Time Frame

24 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Men and women, > 18 years of age Histologically confirmed locally advanced or metastatic melanoma with cutaneous or subcutaneous lesions Immunotherapy treatment naïve subjects (ie, no prior systemic anticancer therapy for unresectable or metastatic melanoma) Scheduled to receive ipilimumab, nivolumab, or combination treatment Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2 Not pregnant or lactating. Women who are of child-bearing potential must agree to use an effective means of birth control (i.e., latex condom, diaphragm, cervical cap, etc) to avoid pregnancy. Informed consent for microarray analysis of locally advanced lesion or skin metastasis retrieved by standard of care biopsy Exclusion Criteria: Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co- stimulation or immune checkpoint pathways Subjects with active, known, or suspected autoimmune disease If considered high-risk and tested for hepatitis: Any positive test result for hepatitis B virus or hepatitis C virus indicating acute or chronic infection Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) Any significant medical condition, laboratory abnormality, or psychiatric illness, that would prevent the subject from participating in the study, places the subject at unacceptable risk if he/she were to participate in the study, or any condition that confounds the ability to interpret data from the study

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Michael Smylie, MB, FRCPC

Phone

780-432-8757

First Name & Middle Initial & Last Name or Official Title & Degree

Alison Schmidt

Phone

780-577-8149

alison.schmidt@ahs.ca

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael Smylie, MB, FRCPC

Organizational Affiliation

Alberta Health services

Official's Role

Principal Investigator

Facility Information:

Facility Name

Cross Cancer Institute

City

Edmonton

State/Province

Alberta

ZIP/Postal Code

T6G 1Z2

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Michael Smylie, M.D.

Phone

780-432-8757

michael.smylie@albertahealthservices.ca

First Name & Middle Initial & Last Name & Degree

Michael Smylie, M.D.

12. IPD Sharing Statement

Plan to Share IPD

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RATIO: Rational Approach To Immuno-Oncology

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