Selection Pressure and Evolution Induced by Immune Checkpoint Inhibitors and Other Immunologic Therapies

NCT02724488 | Active Not Recruiting

• 1 other identifier: SPECIAL-001
• Study Type: observational
• Target: 14
• Locations: 0 countries
• Sites: N/A

Brief Summary

Two part prospective study to:

1. 1.investigate the feasibility of performing ultra-deep sequencing of plasma derived circulating tumor DNA (ctDNA) in individual patients with advanced solid tumors who are currently being treated with immune checkpoint inhibitors (ICIs) and
2. 2.obtain fresh tumor biopsies and serial blood samples to investigate the clonal evolution of tumors under the selection pressure of ICIs.

Conditions

Head and Neck Cancer; Melanoma

Keywords

Advanced cancer; Advanced solid tumors; Phase I clinical trial candidates; Phase II clinical trial candidates; Phase III clinical trial candidates; Head and Neck; Melanoma; Upper Aerodigestive cancer; Oral Cavity; Immune Checkpoint Inhibitors; ICIs; ctDNA; Whole Exome Sequencing; Molecular Profiling

Outcome Measures

Primary Outcomes (2)

• Part 1: The detection of new mutations from circulating tumor DNA (ctDNA) analyses or change in the frequency of mutations found in archival tumor Whole Exome Sequencing (WES) analyses.

  5 years

• Part 2: Concordance between WES analyses of serial tumor biopsies.

  5 years

Secondary Outcomes (5)

• Part 1: Concordance between DNA analyses of archival tumor and ctDNA analyses.

  5 years

• Part 2: Concordance between WES analyses of serial tumor biopsies and ctDNA analyses of serial blood samples.

  5 years

• Part 2: Changes in radiomic signatures of tumors between commencement of immune targeted therapies and disease progression assessed from serial CT scans.

  5 years

• Part 2: Correlation between tumor radiomic signatures from serial CT scans and genomic profiles (WES and gene expression analyses of serial tumor biopsies and ctDNA samples).

  5 years

• Part 2: Changes in levels of immune cells repertoire in peripheral circulation of patients using flow cytometry and related assays.

  5 years

Study Arms (2)

Part 1

Patients with a histological or cytological diagnosis of advanced solid tumors who are currently on immune checkpoint inhibitors will have archival tumor specimens requested and used for whole exome sequencing (WES) of tumor DNA. 3 tubes of blood at a single time point will be collected for ctDNA analysis and germ line DNA analysis (to study normal variants) using next generation sequencing.

Part 2

Patients with a histological or cytological diagnosis of advanced solid tumors who are candidates for a phase I, II, or III clinical trial testing immune checkpoint inhibitors (ICIs) or planning to have treatment with ICIs or other immunological therapy as standard of care will have image-guided fresh tumor core needle biopsy at a maximum of 3 time points: 1) prior to commencement of immune checkpoint inhibitors, 2) when disease response to therapy is confirmed using radiology RECIST 1.1 criteria and/or immune related response criteria, and 3) when radiological disease progression is confirmed by using RECIST 1.1. Blood samples for ctDNA analysis will be collected at the commencement of immunotherapy and every 6-12 weeks thereafter until radiological disease progression is confirmed.

Eligibility Criteria

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

Study Population

PART 1: Patients with a histological or cytological diagnosis of advanced solid tumors who are currently on immune checkpoint inhibitors; fulfill criteria for blood sample collection; and provided written voluntary informed consent. PART 2: Patients with a histological or cytological diagnosis of advanced solid tumors who are candidates for a phase I, II, or III clinical trial testing immune checkpoint inhibitors or planning to have treatment with ICIs or other immunological therapy as standard of care; have at least one biopsiable lesion deemed accessible and safe to biopsy; fulfill our institution's laboratory parameters for tumor biopsy, and provided written voluntary informed consent.

You may qualify if:

• Age \> 18 years.
• Histological or cytological proof of metastatic solid tumors.
• Currently receiving immune checkpoint inhibitors or other immunologic therapies of interest (to be determined by study principal investigators).
• Willingness and ability of patient to provide signed voluntary 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 a venepuncture.
• PART 2:
• Age \> 18 years.
• Histological or cytological proof of metastatic solid tumors.
• At least one biopsiable lesion deemed medically accessible and safe to biopsy.
• Candidate for one or more phase I or II or III clinical trials with immune checkpoint inhibitors at the time of study enrolment. Patients receiving approved immune checkpoint inhibitors or via special access are also eligible. Patients receiving other immunologic therapies of interest may be allowed (to be determined by study principal investigators).
• Fulfills local institution's laboratory parameters for tumor biopsy.
• Willingness and ability of patient to provide signed voluntary informed consent.
• 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 a biopsy procedure.
• Any contraindication to undergoing a venepuncture.

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Princess Margaret Hospital, Canada: collaborator

Biospecimen

Retention: SAMPLES WITH DNA

Part 1: Archival tumor tissue, 3 tubes of whole blood Part 2: Fresh tumor tissue, 5 tubes of whole blood at baseline, serial tubes of whole blood

MeSH Terms

Conditions

Head and Neck Neoplasms; Melanoma

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Lillian Siu, MD

  Princess Margaret Hospital, Canada

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 19, 2015
• First Posted: March 31, 2016
• Study Start: April 1, 2015
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: January 8, 2026

Record last verified: 2026-01