Immune Resistance Interrogation Study

NCT04243720 | Recruiting

• 2 other identifiers: IRISCAPCR ID
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Cancer; Solid Tumor; Metastatic Cancer; Immune Resistance

Keywords

Molecular Profiling; Liquid Biopsy; Tumor Biopsy; Circulation Tumor DNA; Epigenetics; Microbiome; Radiomics; Immune Analysis; Immunohistochemistry

Outcome Measures

Primary Outcomes (4)

• Genomic changes associated with primary or acquired resistance to immunotherapy given alone or in combination in patients with advanced solid tumors

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

  Through study completion, up to 4 years

• Transcriptomic changes associated with primary or acquired resistance to immunotherapy given alone or in combination in patients with advanced solid tumors

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

  Through study completion, up to 4 years

• Immunophenotypic changes associated with primary or acquired resistance to immunotherapy given alone or in combination in patients with advanced solid tumors

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

  Through study completion, up to 4 years

• Epigenetic changes associated with primary or acquired resistance to immunotherapy given alone or in combination in patients with advanced solid tumors

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

  Through study completion, up to 4 years

Secondary Outcomes (4)

• Genomic changes associated with subsequent anticancer therapies in patients with advanced solid tumors who have progressed on immunotherapy

  Through study completion, up to 4 years

• Transcriptomic changes associated with subsequent anticancer therapies in patients with advanced solid tumors who have progressed on immunotherapy

  Through study completion, up to 4 years

• Immunophenotyping changes associated with subsequent anticancer therapies in patients with advanced solid tumors who have progressed on immunotherapy

  Through study completion, up to 4 years

• Epigenetic changes associated with subsequent anticancer therapies in patients with advanced solid tumors who have progressed on immunotherapy

  Through study completion, up to 4 years

Other Outcomes (3)

• Radiomic changes associated with primary or acquired resistance to immunotherapy given alone or in combination in patients with advanced solid tumors

  Through study completion, up to 4 years

• Radiomic changes associated with subsequent anticancer therapies in patients with advanced solid tumors who have progressed on immunotherapy

  Through study completion, up to 4 years

• Fecal microbiome changes associated with primary or acquired resistance to immunotherapy given alone or in combination in patients with advanced solid tumors

  Through study completion, up to 4 years

Study Arms (1)

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

Princess Margaret Cancer Centre

Toronto, Ontario, M5G2M9, Canada

RECRUITING

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.

MeSH Terms

Conditions

Neoplasms; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Lillian Siu, MD

  Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

• Anna Spreafico, MD

  Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Celeste Yu

CONTACT

416-946-4501; celeste.yu@uhn.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2020
• First Posted: January 28, 2020
• Study Start: August 26, 2020
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: June 10, 2026

Record last verified: 2026-06

Locations

CA (1)