Head and Neck CancerSPECIALNCT02724488
Selection Pressure and Evolution Induced by Immune Checkpoint Inhibitors and Other Immunologic Therapies
An observational study of Head and Neck Cancer and Melanoma, run by University Health Network, Toronto.
Trial summary
Two part prospective study to: 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer, Melanoma
- How many people
- 14 participants
- Where
- No sites listed yet
- Study dates
- Apr 2015to Jan 2026
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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.
- Age > 18 years.
- Histological or cytological proof of metastatic solid tumors.
Show all 10Show fewer
- 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.
Who cannot join
- 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:
- 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.
About this study
Two part prospective study to:
- 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
- obtain fresh tumor biopsies and serial blood samples to investigate the clonal evolution of tumors under the selection pressure of ICIs.
Read the detailed description
This feasibility study will be conducted in two parts.
The first part is mainly designed to 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). Patients' archival tumors will be requested and used for whole exome sequencing (WES) of tumor DNA. Blood samples at a single time point will be collected for ctDNA analysis and germ line DNA analysis (to study normal variants) using next generation sequencing.
The second part is designed as a prospective research study in which patients will have tumor and blood samples collected at serial time points to investigate the clonal evolution of tumors under the selection pressure of ICIs. Patients will have image-guided fresh tumor core needle biopsy at a maximum of 3 time points:
- prior to commencement of ICIs, and
- when disease response to therapy is confirmed by standard radiology RECIST 1.1 criteria and/or immune related response criteria, and
- when radiological disease progression on therapy is confirmed by RECIST 1.1 criteria.
Patients who have disease response to immunotherapy could have up to 3 fresh tumor biopsies (all 3 time points) when those who do not respond to therapy will only have one biopsy (1st time point). For patients who will have a mandatory on treatment biopsy as part of a separate clinical trial (within which they are receiving ICIs) at time points different from this study, investigators will request one extra core tumor material for research use within SPECIAL if it is feasible and safe judged by a staff radiologist. Blood samples for ctDNA analysis will be collected at commencement of treatment and every 6-12 weeks thereafter ideally coinciding with radiological tumor assessments whenever possible until radiological disease progression is confirmed using RECIST 1.1 criteria. Normal genomic DNA derived from peripheral mononuclear cells (PBMC) will be extracted from one tube of whole blood collected at baseline to study normal variants. Blood samples for studying changes in immune cells repertoire and immune related amino acids, peptides, proteins and their metabolites in peripheral circulation will be collected at baseline, 6-12 weeks after starting treatment coinciding with the 1st radiological tumor assessment and at the time of radiological disease progression. Imaging parameters for radiomic imaging analysis will be derived from patients' routine CT scans. Fresh tumor biopsies will be used for genomic profiling to study the tumors' mutation spectrum by WES and level of gene expressions. PBMC DNA will be analysed by WES to study normal variants. Mutation profiling of ctDNA will be performed using next generation DNA sequencing approaches.
Genomic data derived from tumor, ctDNA and PBMC DNA analyses will be used to explore tumor clonal architecture and study clonal selection or tumor evolution under selection pressure induced by ICIs or other immunological therapies.
Changes in radiomic imaging signatures during treatment with immune checkpoint inhibitors and their correlation with genomic signatures will also be examined.
Using blood samples collected at baseline, at the time of 1st radiological tumor assessment and at the time of disease progression, dynamic changes in immune cells repertoire and immune related amino acids, peptides, proteins and their metabolites in the peripheral circulation of patients during treatment with ICIs will also be explored.
- 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
- Medical subject headings
- Head and Neck Neoplasms, Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 5 years
Part 2: Concordance between WES analyses of serial tumor biopsies.
Measured: 5 years
Secondary outcomes (5)
Part 1: Concordance between DNA analyses of archival tumor and ctDNA analyses.
Measured: 5 years
Part 2: Concordance between WES analyses of serial tumor biopsies and ctDNA analyses of serial blood samples.
Measured: 5 years
Part 2: Changes in radiomic signatures of tumors between commencement of immune targeted therapies and disease progression assessed from serial CT scans.
Measured: 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).
Measured: 5 years
Part 2: Changes in levels of immune cells repertoire in peripheral circulation of patients using flow cytometry and related assays.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2016 (estimated)
- Study startApr 2015
- Primary completionJan 2026
- Study completionJan 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Princess Margaret Hospital, Canada
- Responsible party
- Sponsor
- Investigators
- Lillian Siu, MD, Principal investigator, Princess Margaret Hospital, Canada
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02724488
- Sponsor's protocol ID
- SPECIAL-001
- Acronym
- SPECIAL
- Status last verified
- Jul 2026
- First submitted
- 19 Nov 2015
- Last updated
- 14 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Selection Pressure and Evolution Induced by Immune Checkpoint Inhibitors and Other Immunologic Therapies
- ClinicalTrials.gov ID
- NCT02724488
- Acronym / sponsor ID
- SPECIAL / SPECIAL-001
- 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
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- Princess Margaret Hospital, Canada
- Study start
- Apr 2015
- Primary completion
- Jan 2026 (actual)
- Study completion
- Jan 2026 (actual)
- First posted
- 31 Mar 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Two part prospective study to:
- 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
- obtain fresh tumor biopsies and serial blood samples to investigate the clonal evolution of tumors under the selection pressure of ICIs.
Detailed description
This feasibility study will be conducted in two parts.
The first part is mainly designed to 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). Patients' archival tumors will be requested and used for whole exome sequencing (WES) of tumor DNA. Blood samples at a single time point will be collected for ctDNA analysis and germ line DNA analysis (to study normal variants) using next generation sequencing.
The second part is designed as a prospective research study in which patients will have tumor and blood samples collected at serial time points to investigate the clonal evolution of tumors under the selection pressure of ICIs. Patients will have image-guided fresh tumor core needle biopsy at a maximum of 3 time points:
- prior to commencement of ICIs, and
- when disease response to therapy is confirmed by standard radiology RECIST 1.1 criteria and/or immune related response criteria, and
- when radiological disease progression on therapy is confirmed by RECIST 1.1 criteria.
Patients who have disease response to immunotherapy could have up to 3 fresh tumor biopsies (all 3 time points) when those who do not respond to therapy will only have one biopsy (1st time point). For patients who will have a mandatory on treatment biopsy as part of a separate clinical trial (within which they are receiving ICIs) at time points different from this study, investigators will request one extra core tumor material for research use within SPECIAL if it is feasible and safe judged by a staff radiologist. Blood samples for ctDNA analysis will be collected at commencement of treatment and every 6-12 weeks thereafter ideally coinciding with radiological tumor assessments whenever possible until radiological disease progression is confirmed using RECIST 1.1 criteria. Normal genomic DNA derived from peripheral mononuclear cells (PBMC) will be extracted from one tube of whole blood collected at baseline to study normal variants. Blood samples for studying changes in immune cells repertoire and immune related amino acids, peptides, proteins and their metabolites in peripheral circulation will be collected at baseline, 6-12 weeks after starting treatment coinciding with the 1st radiological tumor assessment and at the time of radiological disease progression. Imaging parameters for radiomic imaging analysis will be derived from patients' routine CT scans. Fresh tumor biopsies will be used for genomic profiling to study the tumors' mutation spectrum by WES and level of gene expressions. PBMC DNA will be analysed by WES to study normal variants. Mutation profiling of ctDNA will be performed using next generation DNA sequencing approaches.
Genomic data derived from tumor, ctDNA and PBMC DNA analyses will be used to explore tumor clonal architecture and study clonal selection or tumor evolution under selection pressure induced by ICIs or other immunological therapies.
Changes in radiomic imaging signatures during treatment with immune checkpoint inhibitors and their correlation with genomic signatures will also be examined.
Using blood samples collected at baseline, at the time of 1st radiological tumor assessment and at the time of disease progression, dynamic changes in immune cells repertoire and immune related amino acids, peptides, proteins and their metabolites in the peripheral circulation of patients during treatment with ICIs will also be explored.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (10 listed)
- 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.
- Age > 18 years.
Key exclusion criteria (6 listed)
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
Time frame: 5 years
Part 2: Concordance between WES analyses of serial tumor biopsies.
Time frame: 5 years
5 secondary outcomes
Part 1: Concordance between DNA analyses of archival tumor and ctDNA analyses.
Time frame: 5 years
Part 2: Concordance between WES analyses of serial tumor biopsies and ctDNA analyses of serial blood samples.
Time frame: 5 years
Part 2: Changes in radiomic signatures of tumors between commencement of immune targeted therapies and disease progression assessed from serial CT scans.
Time frame: 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).
Time frame: 5 years
Part 2: Changes in levels of immune cells repertoire in peripheral circulation of patients using flow cytometry and related assays.
Time frame: 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2026.
Related trials for Head and Neck Cancer
Not yet recruitingPhase 1/2
177Lu-DOTA-EB-TATE in Adult Patients With Metastatic, Radioactive Iodine Non-Responsive Oncocytic (Hurthle-Cell) Thyroid Cancer
Thyroid Cancer
Active, not recruitingPhase 1/2
A Beta-only IL-2 ImmunoTherapY Study
Advanced Solid Tumor, Unresectable Solid Tumor
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
RecruitingPhase 1
A Study of MGC030 in Participants With Advanced Solid Tumors
Urothelial Cancer, GastroEsophageal Cancer
Not yet recruitingObservational study
Serum Treg/Th17-Related Cytokines and Systemic Inflammatory Indices in Differentiated Thyroid Cancer
Differentiated Thyroid Cancer (DTC), Papillary Thyroid Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lillian Siu, MD principal investigator
Princess Margaret Hospital, Canada
Questions about this trial
What is this clinical trial studying?
An observational study of Head and Neck Cancer and Melanoma, run by University Health Network, Toronto.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2026.