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Immune Resistance Interrogation Study (IRIS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04243720
Recruitment Status : Recruiting
First Posted : January 28, 2020
Last Update Posted : August 28, 2020
Sponsor:
Information provided by (Responsible Party):
University Health Network, Toronto

Brief Summary:
This is a prospective research study which will include patients who have progressed on immunotherapy as their most recent line of therapy. This study aims to characterize whether patients who fail to respond to immunotherapy versus patients who respond initially but after a period of time progress demonstrate different genomic, transcriptomic, epigenetic, immunophenotyping profiles. Patients will have a one-time fresh tumor biopsy. Serial blood samples (total amount of blood drawn may not exceed the lesser of 50 mL or 3 mL/kg in an 8 week period), archival tissue (if available) and one stool sample will be collected.

Condition or disease
Cancer Solid Tumor Metastatic Cancer Immune Resistance

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Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Immune Resistance Interrogation Study
Estimated Study Start Date : August 2020
Estimated Primary Completion Date : February 2024
Estimated Study Completion Date : February 2024

Group/Cohort
IRIS
Patients with a histological or cytological diagnosis of solid malignancies. Patients must have progressed on immunotherapy as their most recent line of therapy.



Primary Outcome Measures :
  1. Genomic changes associated with primary or acquired resistance to immunotherapy given alone or in combination in patients with advanced solid tumors [ Time Frame: Through study completion, up to 4 years ]
  2. Transcriptomic changes associated with primary or acquired resistance to immunotherapy given alone or in combination in patients with advanced solid tumors [ Time Frame: Through study completion, up to 4 years ]
  3. Immunophenotypic changes associated with primary or acquired resistance to immunotherapy given alone or in combination in patients with advanced solid tumors [ Time Frame: Through study completion, up to 4 years ]
  4. Epigenetic changes associated with primary or acquired resistance to immunotherapy given alone or in combination in patients with advanced solid tumors [ Time Frame: Through study completion, up to 4 years ]

Secondary Outcome Measures :
  1. Genomic changes associated with subsequent anticancer therapies in patients with advanced solid tumors who have progressed on immunotherapy [ Time Frame: Through study completion, up to 4 years ]
  2. Transcriptomic changes associated with subsequent anticancer therapies in patients with advanced solid tumors who have progressed on immunotherapy [ Time Frame: Through study completion, up to 4 years ]
  3. Immunophenotyping changes associated with subsequent anticancer therapies in patients with advanced solid tumors who have progressed on immunotherapy [ Time Frame: Through study completion, up to 4 years ]
  4. Epigenetic changes associated with subsequent anticancer therapies in patients with advanced solid tumors who have progressed on immunotherapy [ Time Frame: Through study completion, up to 4 years ]

Other Outcome Measures:
  1. Radiomic changes associated with primary or acquired resistance to immunotherapy given alone or in combination in patients with advanced solid tumors [ Time Frame: Through study completion, up to 4 years ]
  2. Radiomic changes associated with subsequent anticancer therapies in patients with advanced solid tumors who have progressed on immunotherapy [ Time Frame: Through study completion, up to 4 years ]
  3. Fecal microbiome changes associated with primary or acquired resistance to immunotherapy given alone or in combination in patients with advanced solid tumors [ Time Frame: Through study completion, up to 4 years ]

Biospecimen Retention:   Samples With DNA

Peripheral blood samples collected serially for DNA extraction under the LIBERATE protocol.

Archived tumor sample (if available) collected for DNA extraction. Fresh tumor biopsy sample (if available) collected for DNA extraction. Stool sample (if available) collected for DNA extraction.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients with a diagnosis of solid tumor malignancy who progressed on immunotherapy as their most recent line of therapy.
Criteria

Inclusion Criteria:

  • Patients with a histological or cytological diagnosis of solid malignancies, with at least one tumor lesion amenable to core needle biopsy and consent to such a procedure.
  • Patients must have progressed on immunotherapy (defined as anti-PD1/PD-L1 antibodies given as monotherapy or as part of a combination therapy) as their most recent line of therapy. Patients will be classified into two groups: 1) those who benefitted from immunotherapy with either complete response (CR), partial response (PR) or prolonged stable disease (SD) defined as > 6 months with subsequent progression (i.e. acquired resistance), 2) those whose disease is primary refractory to immunotherapy with disease progression on first on-treatment imaging.
  • Patients must be of good performance status, ECOG 0-1, for subsequent anticancer therapy, with either standard treatment or within the context of a clinical trial.
  • Patients must be ≥ 18 years old.
  • Patients must have provided voluntary written informed consent.

Exclusion Criteria:

  • Any condition that could interfere with a patient's ability to provide informed consent such as dementia or severe cognitive impairment.
  • Any contraindication to undergoing venipuncture.
  • Any condition that, in the opinion of the Investigator, would interfere with patient safety, or evaluation of the collected specimens and interpretation of study results.

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): NCT04243720


Contacts
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Contact: Lillian Siu, MD 416-946-4501 CGP@uhn.ca

Locations
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Canada, Ontario
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G2M9
Sponsors and Collaborators
University Health Network, Toronto
Investigators
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Principal Investigator: Lillian Siu, MD Princess Margaret Cancer Centre
Principal Investigator: Anna Spreafico, MD Princess Margaret Cancer Centre
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Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT04243720    
Other Study ID Numbers: IRIS
CAPCR ID ( Other Identifier: 19-6224 )
First Posted: January 28, 2020    Key Record Dates
Last Update Posted: August 28, 2020
Last Verified: August 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Health Network, Toronto:
Molecular Profiling
Liquid Biopsy
Tumor Biopsy
Circulation Tumor DNA
Epigenetics
Microbiome
Radiomics
Immune Analysis
Immunohistochemistry
Additional relevant MeSH terms:
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Neoplasm Metastasis
Neoplastic Processes
Neoplasms
Pathologic Processes