Neoplasms

Symptoms and General Pathology

All Conditions

Neoplasm Metastasis

Neoplastic Processes

All Drugs and Chemicals

Immunomodulating Agents

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

Celeste Yu

Lillian Siu, MD

Anna Spreafico, MD

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.

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.

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.

Immune Resistance Interrogation Study

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).

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

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.

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

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

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

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

University Health Network, Toronto

Digestive System Diseases

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Esophageal Squamous Cell Carcinoma

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Squamous Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Head and Neck Neoplasms

Esophageal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Patients with a histological or cytological confirmed diagnosis of Squamous Cell Cancer of the Head \& Neck, Esophagus or Anal Canal who have radiologically confirmed recurrent or metastatic disease and are commencing on a new treatment or either first-line platinum based chemotherapy or any line immunotherapy.

Elena Elimova, MD

This is prospective research study which will include patients with recurrent or metastatic squamous cell carcinoma of the head and neck, esophagus and anal canal starting on first-line platinum based chemotherapy or any line of immunotherapy treatment.This study aims to characterize the dynamic changes in genomic, epigenetic, immune profiling and imaging data during treatment with systemic therapy. Patients will have archived tumor samples requested as well as blood samples collected at up to four time points to analyze these changes. Imaging data will be derived from patients' routine CT scans before and after treatment.

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

Multi-Omic Assessment of Squamous Cell Cancers Receiving Systemic Therapy

To comprehensively characterize genomic, epigenetic and immune profiling features and changes in longitudinal blood samples that are associated with systemic treatment of recurrent or metastatic squamous cell cancers of the head \& neck, esophagus and anal canal.

To establish a clinically annotated biorepository of archived tumor and longitudinal blood samples, with serial radiomic evaluations in patients with recurrent/metastatic squamous cell cancers commencing on any new systemic treatments.

To correlate genomic, othr-omic, radiomic and immune profiling results with clinical outcome - to identify potential predictive markers of response/resistance to systemic therapy.

To compare HPV-positive and HPV-negative squamous cell histology across three disease sites with multi-omic assessment.

To investigate whether any correlation or relation exists between tumor genomic profiles and radiomic imaging signatures.

To enable data sharing with Queen's University Belfast as a collaborative initiative based on this project

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Immune Resistance Interrogation Study	NCT04243720	Cancer Solid Tumor Metastatic Canc... Immune Resistan...		18 Years -	University Health Network, Toronto
Multi-Omic Assessment of Squamous Cell Cancers Receiving Systemic Therapy	NCT03712566	Cancer Esophagus Squam... Squamous Cell C... Anal Canal Squa... Metastatic Canc...		18 Years -	University Health Network, Toronto

Spots Global Cancer Trial Database for immune analysis