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Immune Resistance Interrogation Study (IRIS)

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ClinicalTrials.gov Identifier: NCT04243720
Recruitment Status : Recruiting
First Posted : January 28, 2020
Last Update Posted : March 12, 2024
Sponsor:
Information provided by (Responsible Party):
University Health Network, Toronto

Study Description
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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

Detailed Description:
Although there has been some success with the use of immunotherapy treatments specifically antibodies that block the programmed death 1 receptor (PD1/L1), the majority of cancer patients either fail to respond (primary resistance) or respond initially but progress after a period of time (acquired resistance) when treated with immunotherapy agents. The hypothesis being tested is whether patients who have primary versus acquired resistance to immunotherapy demonstrate different genomic, transcriptomic, immunophenotypic and/or epigenetic profiles.
Study Design
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Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Immune Resistance Interrogation Study
Actual Study Start Date : August 26, 2020
Estimated Primary Completion Date : February 2025
Estimated Study Completion Date : February 2025
Groups and Cohorts
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Group/Cohort
Immune Resistance Interrogation Study (IRIS)
Patients with a histological or cytological diagnosis of solid malignancies. Patients must have progressed on immunotherapy as their most recent line of therapy.


Outcome Measures
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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 ]
    The genomic parameters for radiomic imaging analysis will be derived from patients' routine CT scans to study changes in radiomic signatures during treatment.

  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 ]
    The transcriptomic parameters for radiomic imaging analysis will be derived from patients' routine CT scans to study changes in radiomic signatures during treatment.

  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 ]
    The immunophenotypic parameters for radiomic imaging analysis will be derived from patients' routine CT scans to study changes in radiomic signatures during treatment.

  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 ]
    The epigenetic parameters for radiomic imaging analysis will be derived from patients' routine CT scans to study changes in radiomic signatures during treatment.


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 ]
    The genomic parameters for radiomic imaging analysis will be derived from patients' routine CT scans to study changes in radiomic signatures during treatment.

  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 ]
    The transcriptomic parameters for radiomic imaging analysis will be derived from patients' routine CT scans to study changes in radiomic signatures during treatment.

  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 ]
    The immunophenotypic parameters for radiomic imaging analysis will be derived from patients' routine CT scans to study changes in radiomic signatures during treatment.

  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 ]
    The epigenetic parameters for radiomic imaging analysis will be derived from patients' routine CT scans to study changes in radiomic signatures during treatment.


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 ]
    Dynamic changes in radiomic signatures of tumors between commencement of systemic treatment and disease progression will be analysed from serial CT scans (normally performed at base line and approximately every 2-3 months thereafter until disease progression).

  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 ]
    Tumor radiomic signatures will be used to study how phenotypic characteristics of tumors change during systemic therapy and how these signatures correlate with genomic, transcriptomic, immunophenotypic and epigenetic signatures

  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 ]
    DNA extraction will be performed and subjected to Shotgun sequencing. Bioinformatic analysis will be performed to determine microbial taxa composition (operation taxa units - OTU's) and diversity, including abundance plots at class, genus and species levels, alpha diversity (Rarefaction curve, Shannon curve, Rank Abundance curve) and beta diversity ((Un)weighted unifrac distance, PCoA) plots.


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.


Eligibility Criteria
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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) lasting at least 6 months with subsequent progression or who had disease progression after at least 12 weeks from the last dose of immunotherapy in the adjuvant setting (i.e. acquired resistance), 2) those whose disease is primary refractory to immunotherapy with disease progression at their first on-treatment imaging, those who benefitted from immunotherapy with stable disease (SD) but progressed in <6 months or those that had progressive disease earlier than 12 weeks from the last dose of immunotherapy in the adjuvant setting.
  • 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.
Contacts and Locations
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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: Celeste Yu 416-946-4501 ext 5281 celeste.yu@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
More Information
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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: March 12, 2024
Last Verified: March 2024

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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