Squamous Cell Carcinoma of the Head and NeckPhase 2NCT03057613
The Addition of Pembrolizumab to Postoperative Radiotherapy in Cutaneous Squamous Cell Cancer of the Head and Neck
A Phase 2 study testing Pembrolizumab and IMRT 60-66Gy in people with Squamous Cell Carcinoma of the Head and Neck, run by Case Comprehensive Cancer Center at 2 sites in United States.
Trial summary
A small group of skin cancers of the head and neck, called resected cutaneous squamous carcinomas, are more aggressive than most cancers of this type, even after being treated with standard therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Squamous Cell Carcinoma of the Head and Neck
- What is being tested?
- Pembrolizumab and IMRT 60-66Gy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 2 sitesUnited States
- Study dates
- 10 May 2017to 9 Sep 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
Who may be able to join
- Histologic diagnosis of cutaneous squamous cell carcinoma of the head and neck that has been resected with no evidence of gross residual disease (margin positivity is acceptable)
- Patients must have undergone resection of the disease and demonstrate high risk pathologic features including:
- T4
- Node positive disease
- T2/T3N0 disease with any 1 additional feature, including:
- Recurrent Disease
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- Perineural invasion
- Lymphovascular space invasion
- Poorly differentiated histology
- Positive Margins
- Satellitosis or in-transit metastases
- Patients are required to have computerized tomography (CT) neck and chest or positron emission tomography/computerized tomography (PET/CT) and have no documented evidence of distant metastases
- Patients must not have a history of the following immunosuppressive conditions:bone marrow transplantation and/or organ transplants and/or chronic rheumatic conditions that require active immunosuppressive therapy. Patients with a history of chronic lymphoid or leukemic malignancies which are not under active therapy (no active therapy within the last 3 months) will be eligible. Patients with chronic lymphoid or leukemic malignancies are eligible with or without active disease as long as they have not had treatment within the past three months.
- Patients may not have had prior therapy with a checkpoint inhibitor (e.g. anti-CTLA-4, anti-PD-1 or anti-PD-L1 therapy)
- Patients may not have had prior radiotherapy (>30Gy) to the area requiring treatment that would result in any overlap of tissue in both fields
- Patients may have received chemotherapy or radiation for a previous, curatively treated malignancy provided at least 2 years have elapsed and there is no current evidence of disease (patients with previous or concurrent additional skin cancers are eligible)
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
- Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
- Patients must have adequate laboratory values
- Absolute neutrophil count ≥ 1,500/mcL
- Platelets ≥ 100,000/mcL
- Hemoglobin ≥ 9g/dL or ≥5.6mmol/L without transfusion
- Serum creatinine ≤ 1.5 times upper limit of normal (ULN) or measured creatinine clearance ≥60mL/min for subject with creatinine levels >1.5 times institutional ULN
- Serum bilirubin ≤ 1.5 times ULN or direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN
- Aspartate aminotransferase (AST (SGOT)) and alanine aminotransferase (ALT (SPGT)) ≤ 2.5 times ULN or ≤ 5 times ULN for subjects with liver metastases
- Albumin ≥ 2.5mg/dL
Who cannot join
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- Has a known history of active Bacillus Tuberculosis (TB)
- Hypersensitivity to pembrolizumab.
- Has a history of the following immunosuppressive conditions: bone marrow transplantation, and/or organ transplants and/or chronic rheumatic conditions that require active immunosuppressive therapy. Patients with chronic lymphoid/leukemic malignancies that have undergone treatment in the last 3 months will be ineligible.
- Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e.≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- Has had prior chemotherapy, targeted small molecule therapy, or radiotherapy within 2 weeks prior to study Day 1 or who has not recovered (i.e. ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
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- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or a separate primary squamous cell carcinoma of the skin or a separate primary squamous cell carcinoma of the skin. Patients with chronic lymphoid or leukemic malignancies are eligible with or without active disease as long as they have not had treatment within the past three months.
- Has metastatic disease.
- Has known history of, or any evidence of active, non-infectious pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA is detected).
- Has received a live vaccine within 30 days of planned start of study therapy.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, 44195
About this study
Official title: A Phase II Study of the Addition of Pembrolizumab to Postoperative Radiotherapy in Resected High Risk Cutaneous Squamous Cell Cancer of the Head and Neck
A small group of skin cancers of the head and neck, called resected cutaneous squamous carcinomas, are more aggressive than most cancers of this type, even after being treated with standard therapy. This trial will use stronger treatment to look at the safety and effectiveness (efficacy) of combining a drug called Pembrolizumab with radiation after a cancer has already been treated to suppress secondary tumor formation in high risk cutaneous squamous cell cancer of the head and neck.
Primary Objective To assess safety by looking at the people with dose limiting responses
Read the detailed description
Primary Objective:
To assess safety and estimate 1-year progression-free survival (PFS) of postoperative radiation therapy (RT) + concurrent and adjuvant Pembrolizumab in high risk resected cutaneous squamous cell cancer of the head and neck (cSCC-HN).
Secondary Objectives
- To evaluate the relationship of baseline programmed death-ligand 1 (PD-L1) expression by tumor and tumor-infiltrating lymphocytes (TILs) to preliminary efficacy .
- To phenotype tumor infiltrating lymphocytes and peripheral blood lymphocytes (PBLs), and investigate tumor suppressor populations including Tregs, myeloid-derived suppressor cells (MDSCs) and cluster of differentiation 8 (CD8) suppressor cells and assess ex vivo for effector function by cytokine production and cytotoxicity assays as well as suppressor function in assays with autologous PBLs.
- To evaluate the tumor microenvironment (TME), and immune markers at the invasive margin of the tumor, including CD8, PD-1, PD-L1, TIM-3, galectin-9 or HMGB-1, BTLA and HVEM, as well as Lag-3, CTLA-4 and others.
- To evaluate the genomic and/or transcriptomic profile of these tumors using RNA-seq /Whole Transcriptome Shotgun Sequencing
Trial Design:
This is a phase II trial evaluating the addition of concurrent and adjuvant fixed-dose pembrolizumab in combination with standard intensity-modulated radiation therapy (IMRT), in order to establish safety and estimate efficacy of this regimen to be tested in a subsequent randomized registration trial.
Thirty seven patients will be enrolled.
- Being tested
- Pembrolizumab, IMRT 60-66Gy
- Keywords
- radiation, resected
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
200mg every 3 weeks for 16 weeks given by IV infusion
IMRT 60-66GyRadiation
60-66Gy for 6 weeks
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab + post operative radiotherapy | Experimental | IMRT 60-66Gy for 6 weeks in combination with Pembrolizumab every 3 weeks for 16 weeks Receives: Drug: Pembrolizumab; Radiation: IMRT 60-66Gy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With Dose Limiting Toxicities
There will be an initial safety run in cohort consisting of an initial safety run in cohort consisting of eight patients to allow for at least six evaluable patients for dose limiting toxicities (DLTs) by the week 20 visit. If a total of 0-2 of the initial six evaluable patients experience DLTs, the safety run in will have been deemed successful and the 29 remaining planned patients will be accrued. DLT for this study is defined as the occurrence of a severe adverse event (AE) that is at least possibly related to pembrolizumab, and occurs from the initiation of treatment thru 30 days after the final administration of the study treatment
Measured: Up to 20 weeks post treatment
Number of Participants With Progression Free Survival
Progression-free survival (PFS) will be calculated from treatment initiation to disease progression or death from any cause or last follow up
Measured: Up to 1 year after beginning treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2017
- Study start10 May 2017
- Primary completion26 Jun 2020
- Study completion9 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Squamous Cell Carcinoma of the Head and NeckStudies of the same condition, open and under way.
- More trials run by Case Comprehensive Cancer CenterThe 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Shlomo Koyfman, MD, Principal investigator, Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03057613
- Sponsor's protocol ID
- CASE6316
- Status last verified
- Jun 2022
- First submitted
- 14 Feb 2017
- Last updated
- 30 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of the Addition of Pembrolizumab to Postoperative Radiotherapy in Resected High Risk Cutaneous Squamous Cell Cancer of the Head and Neck
- ClinicalTrials.gov ID
- NCT03057613
- Acronym / sponsor ID
- CASE6316
- Keywords
- radiation, resected
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Case Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- 10 May 2017 (actual)
- Primary completion
- 26 Jun 2020 (actual)
- Study completion
- 9 Sep 2020 (actual)
- First posted
- 20 Feb 2017 (actual)
- Results
- Posted 19 Oct 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A small group of skin cancers of the head and neck, called resected cutaneous squamous carcinomas, are more aggressive than most cancers of this type, even after being treated with standard therapy. This trial will use stronger treatment to look at the safety and effectiveness (efficacy) of combining a drug called Pembrolizumab with radiation after a cancer has already been treated to suppress secondary tumor formation in high risk cutaneous squamous cell cancer of the head and neck.
Primary Objective To assess safety by looking at the people with dose limiting responses
Detailed description
Primary Objective:
To assess safety and estimate 1-year progression-free survival (PFS) of postoperative radiation therapy (RT) + concurrent and adjuvant Pembrolizumab in high risk resected cutaneous squamous cell cancer of the head and neck (cSCC-HN).
Secondary Objectives
- To evaluate the relationship of baseline programmed death-ligand 1 (PD-L1) expression by tumor and tumor-infiltrating lymphocytes (TILs) to preliminary efficacy .
- To phenotype tumor infiltrating lymphocytes and peripheral blood lymphocytes (PBLs), and investigate tumor suppressor populations including Tregs, myeloid-derived suppressor cells (MDSCs) and cluster of differentiation 8 (CD8) suppressor cells and assess ex vivo for effector function by cytokine production and cytotoxicity assays as well as suppressor function in assays with autologous PBLs.
- To evaluate the tumor microenvironment (TME), and immune markers at the invasive margin of the tumor, including CD8, PD-1, PD-L1, TIM-3, galectin-9 or HMGB-1, BTLA and HVEM, as well as Lag-3, CTLA-4 and others.
- To evaluate the genomic and/or transcriptomic profile of these tumors using RNA-seq /Whole Transcriptome Shotgun Sequencing
Trial Design:
This is a phase II trial evaluating the addition of concurrent and adjuvant fixed-dose pembrolizumab in combination with standard intensity-modulated radiation therapy (IMRT), in order to establish safety and estimate efficacy of this regimen to be tested in a subsequent randomized registration trial.
Thirty seven patients will be enrolled.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab + post operative radiotherapy | Experimental | Drug: Pembrolizumab, Radiation: IMRT 60-66GyIMRT 60-66Gy for 6 weeks in combination with Pembrolizumab every 3 weeks for 16 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- Histologic diagnosis of cutaneous squamous cell carcinoma of the head and neck that has been resected with no evidence of gross residual disease (margin positivity is acceptable)
- Patients must have undergone resection of the disease and demonstrate high risk pathologic features including:
- Patients are required to have computerized tomography (CT) neck and chest or positron emission tomography/computerized tomography (PET/CT) and have no documented evidence of distant metastases
- Patients must not have a history of the following immunosuppressive conditions:bone marrow transplantation and/or organ transplants and/or chronic rheumatic conditions that require active immunosuppressive therapy. Patients with a history of chronic lymphoid or leukemic malignancies which are not under active therapy (no active therapy within the last 3 months) will be eligible. Patients with chronic lymphoid or leukemic malignancies are eligible with or without active disease as long as they have not had treatment within the past three months.
- Patients may not have had prior therapy with a checkpoint inhibitor (e.g. anti-CTLA-4, anti-PD-1 or anti-PD-L1 therapy)
Key exclusion criteria (16 listed)
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- Has a known history of active Bacillus Tuberculosis (TB)
- Hypersensitivity to pembrolizumab.
- Has a history of the following immunosuppressive conditions: bone marrow transplantation, and/or organ transplants and/or chronic rheumatic conditions that require active immunosuppressive therapy. Patients with chronic lymphoid/leukemic malignancies that have undergone treatment in the last 3 months will be ineligible.
- Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e.≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pembrolizumab200mg every 3 weeks for 16 weeks given by IV infusion | Drug | Pembrolizumab + post operative radiotherapy |
| IMRT 60-66Gy60-66Gy for 6 weeks | Radiation | Pembrolizumab + post operative radiotherapy |
Primary outcome
Number of Subjects With Dose Limiting Toxicities
Time frame: Up to 20 weeks post treatment
There will be an initial safety run in cohort consisting of an initial safety run in cohort consisting of eight patients to allow for at least six evaluable patients for dose limiting toxicities (DLTs) by the week 20 visit. If a total of 0-2 of the initial six evaluable patients experience DLTs, the safety run in will have been deemed successful and the 29 remaining planned patients will be accrued. DLT for this study is defined as the occurrence of a severe adverse event (AE) that is at least possibly related to pembrolizumab, and occurs from the initiation of treatment thru 30 days after the final administration of the study treatment
Number of Participants With Progression Free Survival
Time frame: Up to 1 year after beginning treatment
Progression-free survival (PFS) will be calculated from treatment initiation to disease progression or death from any cause or last follow up
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Shlomo Koyfman, MD principal investigator
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab and IMRT 60-66Gy in people with Squamous Cell Carcinoma of the Head and Neck, run by Case Comprehensive Cancer Center at 2 sites in United States.
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 28 inclusion and 16 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 30 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Subjects With Dose Limiting Toxicities (time frame: Up to 20 weeks post treatment). 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 30 Jun 2022.