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Microarray Prediction of Response to Nivolumab, Ipilimumab, or Combined Therapy in Subjects With Previously Untreated, Locally Advanced or Metastatic Melanoma (RATIO)

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ClinicalTrials.gov Identifier: NCT02700971
Recruitment Status : Recruiting
First Posted : March 7, 2016
Last Update Posted : August 19, 2016
Sponsor:
Collaborator:
Transplant Genomics, Inc.
Information provided by (Responsible Party):
AHS Cancer Control Alberta

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.

Condition or disease Intervention/treatment Phase
Metastatic Melanoma Procedure: Molecular Microscope Diagnostic system Not Applicable

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
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 Start Date : June 2016
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Biopsy Melanoma
Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: Cutaneous Biopsy for microarray analysis
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.
Procedure: Molecular Microscope Diagnostic system
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 Measures :
  1. Correlation of the MMDx from pretreatment biopsy with overall response rate (ORR). [ Time Frame: 24 months ]

Secondary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: 24 months ]
  2. Overall Survival (OS) [ Time Frame: 24 months ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02700971


Contacts
Contact: Michael Smylie, MB, FRCPC 780-432-8757
Contact: Suzanne Marney 780-577-8149 suzanne.marney@ahs.ca

Locations
Canada, Alberta
Cross Cancer Institute Recruiting
Edmonton, Alberta, Canada, T6G 1Z2
Contact: Michael Smylie, M.D.    780-432-8757    michael.smylie@albertahealthservices.ca   
Principal Investigator: Michael Smylie, M.D.         
Sponsors and Collaborators
AHS Cancer Control Alberta
Transplant Genomics, Inc.
Investigators
Principal Investigator: Michael Smylie, MB, FRCPC Alberta Health Services

Responsible Party: AHS Cancer Control Alberta
ClinicalTrials.gov Identifier: NCT02700971     History of Changes
Other Study ID Numbers: IIT-RATIO-CCI-01
First Posted: March 7, 2016    Key Record Dates
Last Update Posted: August 19, 2016
Last Verified: August 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Nivolumab
Antineoplastic Agents