Squamous Cell Carcinoma of the Oral CavityPhase 2NICONCT03721757
CA209-891: Neoadjuvant and Adjuvant Nivolumab as Immune Checkpoint Inhibition in Oral Cavity Cancer
A Phase 2 study testing Nivolumab, Surgery, Radiotherapy and Nivolumab, Surgery, Chemoradiotherapy in people with Squamous Cell Carcinoma of the Oral Cavity, run by The Clatterbridge Cancer Centre NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
This trial is to investigate the use of nivolumab in sequence with standard of care surgery and radiation/chemoradiation in locally advanced oral cavity Squamous cell carcinoma of the oral cavity. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Squamous Cell Carcinoma of the Oral Cavity
- What is being tested?
- Nivolumab, Surgery, Radiotherapy and Nivolumab, Surgery, Chemoradiotherapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 10 May 2019to 24 Feb 2025
- Phase
- Phase 2
- 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
Who may be able to join
None listed.
Who cannot join
- Tumours staged as T4 on the basis of bone invasion only and in the absence of nodal metastases.
- Distant metastases detected, or suspected on imaging
- Unfit for chemoradiotherapy, due to comorbidity.
- Previous malignancy requiring treatment within the last 3 years (with the exception of non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, oesophageal endometrial, cervical/dysplasia, melanoma, or breast). Prior head and neck cancer within the last three years is allowed if the tumour was treated with surgery only, and did not require radiotherapy.
- Prior head and neck radiotherapy
- On immunosuppressive medication (including steroids at dose equivalent to prednisolone >10mg/day unless used as replacement therapy).
Show all 10Show fewer
- Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, lichen planus or other conditions not expected to recur in the absence of an external trigger are permitted to enrol.
- Known human immunodeficiency virus (HIV) or viral hepatitis infection.
- Women who are pregnant or breastfeeding
- Known medical condition that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Clatterbridge Cancer Centre NHS Foundation Trust
Bebington, CH634JY
About this study
Official title: NICO - CA209-891: Neoadjuvant and Adjuvant Nivolumab as Immune Checkpoint Inhibition in Oral Cavity Cancer
This trial is to investigate the use of nivolumab in sequence with standard of care surgery and radiation/chemoradiation in locally advanced oral cavity Squamous cell carcinoma of the oral cavity.
Read the detailed description
Squamous cell carcinoma of the oral cavity is usually treated with surgery, often followed by radiation therapy with or without chemotherapy. Unfortunately despite this treatment, it recurs or spreads in about half of patients. In this trial the investigators aim to investigate the use of nivolumab in sequence with standard of care surgery and radiation/chemoradiation.
Following confirmation of eligibility patients will be treated with a single dose of nivolumab 1-2 weeks prior to surgery to remove their tumour. Based on pathological risk factors determined following surgery, patients will be assigned to undergo adjuvant radiotherapy or chemoradiotherapy. Patients with high risk criteria (Extra capsular spread, involved margins) will be assigned to chemoradiotherapy. A further single dose of nivolumab will be given between surgery and commencement of radiotherapy or chemoradiotherapy.
Following completion of chemo/radiation, patients will commence adjuvant nivolumab, with a total of 6 doses given at 4 weekly intervals. Patients will be followed up for 12 months post surgery.
The primary objectives of this trial is to determine disease free survival at 12 months post surgery and the feasibility of recruiting to both cohorts.
- Being tested
- Nivolumab, Surgery, Radiotherapy, Nivolumab, Surgery, Chemoradiotherapy
- Keywords
- Head and Neck cancer, Squamous cell carcinoma
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Head and Neck Neoplasms, Carcinoma, Squamous Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nivolumab, Surgery, RadiotherapyBiological
Also called Curative Surgery, Adjuvant Radiotherapy
A single dose of nivolumab 7-14 days before curative surgery. A further single dose will be administered following surgery and prior to radiotherapy commencing. Six further doses of nivolumab will be received post radiotherapy
Nivolumab, Surgery, ChemoradiotherapyBiological
Also called Curative surgery, Adjuvant chemoradiotherapy
A single dose of nivolumab 7-14 days before curative surgery. A further single dose will be administered following surgery and prior to Chemoradiotherapy (cisplatin) commencing. Six further doses of nivolumab will be received post radiotherapy
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab, Surgery, Radiotherapy | Other | Patients will be treated with a single dose of nivolumab (240mg flat dose), followed by surgery to remove their tumour within 1-2 weeks.
Based on pathological risk factors determined following surgery, patients will be assigned to undergo adjuvant radiotherapy or chemoradiotherapy. Patients with low risk criteria following surgery will be assigned to radiotherapy.
A single dose of nivolumab (240mg flat dose) will be given between surgery and commencement of radiotherapy (1-2 weeks prior).
Radiotherapy will be administered over 30 fractions i.e. over 30 days (Monday to Friday for 6 consecutive weeks).
Following completion of radiation (within 1-2 weeks), patients will commence adjuvant nivolumab, with a total of 6 doses (480mg flat dose) given at 4 weekly intervals Receives: Biological: Nivolumab, Surgery, Radiotherapy |
| Nivolumab, Surgery, Chemoradiotherapy | Other | Patients will be treated with a single dose of nivolumab (240mg flat dose), followed by surgery to remove their tumour within 1-2 weeks.
Based on pathological risk factors determined following surgery, patients will be assigned to undergo adjuvant radiotherapy or chemoradiotherapy. Patients with high risk criteria following surgery will be assigned to chemoradiotherapy.
A single dose of nivolumab (240mg flat dose) will be given between surgery and chemoradiotherapy (1-2 weeks prior).
Chemoradiotherapy will be administered over 30 fractions i.e. over 30 days with concomitant Cisplatin (100mg/m2) on day 1 and 21.
Following completion of radiation (within 1-2 weeks), patients will commence adjuvant nivolumab, with a total of 6 doses (480mg flat dose) given at 4 weekly intervals. Receives: Biological: Nivolumab, Surgery, Chemoradiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease free survival
1 year disease free survival defined as disease recurrence or death at 12 months from surgery
Measured: Patients will be followed up for 12 months following surgery
Recruitment Rate
Measured as the number of patients/site/month
Measured: Period of recruitment
Secondary outcomes (8)
Overall survival
Overall survival measured as the time from surgery to death by any cause
Measured: Patients will be followed up for 12 months following surgery
Surgical complications - Infection rate
Measured as incidence of post surgical infection
Measured: up to 8 weeks post date of surgery
Surgical complications - length of hospital admission
Measured as length of time between admission for surgery and discharge
Measured: up to 8 weeks post date of surgery
Surgical complications - free flap failure
Measured as incidence of failure of free flap reconstruction
Measured: up to 8 weeks post date of surgery
Surgical complications - perioperative (30-day mortality)
Measured as Incidence of death post surgery by any cause
Measured: up to 30 days post date of surgery
Assessment of adverse events
Assessment of adverse events, adverse events recorded will be classified using CTCAE v4
Measured: Following participants informed consent up to 100 days following last dose of trial treatment.
The change of Quality of Life: EORTC QLQ-C30 v3
The change of quality of life is measured using the EORTC QLQ-C30 v3 quality of life questionnaire. The quality of life scale is transformed into a score of 0 to 100, derived by a 4-point Likert scale. A higher score represents a higher level of quality of life.
Measured: Patients will be followed up for 12 months following surgery
The change of symptom
The change of symptoms is measured using the EORTC quality of life questionnaire (EORTC QLQ) Head and Neck cancer module (QLQ-H\&N35). The symptom scale is transformed into a score of 0 to 100, derived by a 4-point Likert scale. A higher score represents a higher level of symptom.
Measured: Patients will be followed up for 12 months following surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2018
- Study start10 May 2019
- Primary completion24 Feb 2025
- Study completion24 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Squamous Cell Carcinoma of the Oral CavityStudies of the same condition, open and under way.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Clatterbridge Cancer Centre NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University of Liverpool, Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Joseph Sacco, MBChB, Principal investigator, University of Liverpool
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03721757
- Sponsor's protocol ID
- C0947
- Other IDs
- 2017-005015-13, ISRCTN17428671, CA209-891, 2017
- Acronym
- NICO
- Status last verified
- Feb 2025
- First submitted
- 23 Jul 2018
- Last updated
- 25 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NICO - CA209-891: Neoadjuvant and Adjuvant Nivolumab as Immune Checkpoint Inhibition in Oral Cavity Cancer
- ClinicalTrials.gov ID
- NCT03721757
- Acronym / sponsor ID
- NICO / C0947
- Keywords
- Head and Neck cancer, Squamous cell carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- The Clatterbridge Cancer Centre NHS Foundation TrustUniversity, hospital or other
- Collaborators
- University of Liverpool, Bristol-Myers Squibb
- Study start
- 10 May 2019 (actual)
- Primary completion
- 24 Feb 2025 (actual)
- Study completion
- 24 Feb 2025 (actual)
- First posted
- 26 Oct 2018 (actual)
- 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.
This trial is to investigate the use of nivolumab in sequence with standard of care surgery and radiation/chemoradiation in locally advanced oral cavity Squamous cell carcinoma of the oral cavity.
Detailed description
Squamous cell carcinoma of the oral cavity is usually treated with surgery, often followed by radiation therapy with or without chemotherapy. Unfortunately despite this treatment, it recurs or spreads in about half of patients. In this trial the investigators aim to investigate the use of nivolumab in sequence with standard of care surgery and radiation/chemoradiation.
Following confirmation of eligibility patients will be treated with a single dose of nivolumab 1-2 weeks prior to surgery to remove their tumour. Based on pathological risk factors determined following surgery, patients will be assigned to undergo adjuvant radiotherapy or chemoradiotherapy. Patients with high risk criteria (Extra capsular spread, involved margins) will be assigned to chemoradiotherapy. A further single dose of nivolumab will be given between surgery and commencement of radiotherapy or chemoradiotherapy.
Following completion of chemo/radiation, patients will commence adjuvant nivolumab, with a total of 6 doses given at 4 weekly intervals. Patients will be followed up for 12 months post surgery.
The primary objectives of this trial is to determine disease free survival at 12 months post surgery and the feasibility of recruiting to both cohorts.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nivolumab, Surgery, Radiotherapy | Other | Biological: Nivolumab, Surgery, RadiotherapyPatients will be treated with a single dose of nivolumab (240mg flat dose), followed by surgery to remove their tumour within 1-2 weeks. Based on pathological risk factors determined following surgery, patients will be assigned to undergo adjuvant radiotherapy or chemoradiotherapy. Patients with low risk criteria following surgery will be assigned to radiotherapy. A single dose of nivolumab (240mg flat dose) will be given between surgery and commencement of radiotherapy (1-2 weeks prior). Radiotherapy will be administered over 30 fractions i.e. over 30 days (Monday to Friday for 6 consecutive weeks). Following completion of radiation (within 1-2 weeks), patients will commence adjuvant nivolumab, with a total of 6 doses (480mg flat dose) given at 4 weekly intervals |
| Nivolumab, Surgery, Chemoradiotherapy | Other | Biological: Nivolumab, Surgery, ChemoradiotherapyPatients will be treated with a single dose of nivolumab (240mg flat dose), followed by surgery to remove their tumour within 1-2 weeks. Based on pathological risk factors determined following surgery, patients will be assigned to undergo adjuvant radiotherapy or chemoradiotherapy. Patients with high risk criteria following surgery will be assigned to chemoradiotherapy. A single dose of nivolumab (240mg flat dose) will be given between surgery and chemoradiotherapy (1-2 weeks prior). Chemoradiotherapy will be administered over 30 fractions i.e. over 30 days with concomitant Cisplatin (100mg/m2) on day 1 and 21. Following completion of radiation (within 1-2 weeks), patients will commence adjuvant nivolumab, with a total of 6 doses (480mg flat dose) given at 4 weekly intervals. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (10 listed)
- Tumours staged as T4 on the basis of bone invasion only and in the absence of nodal metastases.
- Distant metastases detected, or suspected on imaging
- Unfit for chemoradiotherapy, due to comorbidity.
- Previous malignancy requiring treatment within the last 3 years (with the exception of non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, oesophageal endometrial, cervical/dysplasia, melanoma, or breast). Prior head and neck cancer within the last three years is allowed if the tumour was treated with surgery only, and did not require radiotherapy.
- Prior head and neck radiotherapy
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 |
|---|---|---|
| Nivolumab, Surgery, RadiotherapyAlso: Curative Surgery, Adjuvant RadiotherapyA single dose of nivolumab 7-14 days before curative surgery. A further single dose will be administered following surgery and prior to radiotherapy commencing. Six further doses of nivolumab will be received post radiotherapy | Biological | Nivolumab, Surgery, Radiotherapy |
| Nivolumab, Surgery, ChemoradiotherapyAlso: Curative surgery, Adjuvant chemoradiotherapyA single dose of nivolumab 7-14 days before curative surgery. A further single dose will be administered following surgery and prior to Chemoradiotherapy (cisplatin) commencing. Six further doses of nivolumab will be received post radiotherapy | Biological | Nivolumab, Surgery, Chemoradiotherapy |
Primary outcome
Disease free survival
Time frame: Patients will be followed up for 12 months following surgery
1 year disease free survival defined as disease recurrence or death at 12 months from surgery
Recruitment Rate
Time frame: Period of recruitment
Measured as the number of patients/site/month
8 secondary outcomes
Overall survival
Time frame: Patients will be followed up for 12 months following surgery
Surgical complications - Infection rate
Time frame: up to 8 weeks post date of surgery
Surgical complications - length of hospital admission
Time frame: up to 8 weeks post date of surgery
Surgical complications - free flap failure
Time frame: up to 8 weeks post date of surgery
Surgical complications - perioperative (30-day mortality)
Time frame: up to 30 days post date of surgery
Assessment of adverse events
Time frame: Following participants informed consent up to 100 days following last dose of trial treatment.
The change of Quality of Life: EORTC QLQ-C30 v3
Time frame: Patients will be followed up for 12 months following surgery
The change of symptom
Time frame: Patients will be followed up for 12 months following surgery
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 25 Feb 2025.
- Individual participant dataSharing planned: No
Related trials for Squamous Cell Carcinoma of the Oral Cavity
RecruitingPhase 2
Proton Spatially Fractionated Radiotherapy or Photon Stereotactic Body Radiotherapy in Combination With Pembrolizumab Before Surgery for the Treatment of Locally Advanced and Radiation-Naive Locoregionally Recurrent Oral Cavity Cancer, OSPRI Trial
Locally Advanced Oral Cavity Squamous Cell Carcinoma, Locally Recurrent Oral Cavity Squamous Cell Carcinoma
RecruitingObservational study
Defining the Natural History of Squamous Cell Carcinoma in Fanconi Anemia
Fanconi Anemia, Inherited Bone Marrow Failure Syndrome
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 3
Testing the Addition of Anti-Cancer Drug, Cetuximab, to Standard of Care Treatment (Pembrolizumab) for Returning or Spreading Head and Neck Cancer After Previous Treatment
Metastatic Head and Neck Squamous Cell Carcinoma, Metastatic Hypopharyngeal Squamous Cell Carcinoma
RecruitingObservational study
Head and Neck Carcinoma Clinical Research Platform for Molecular and Blood-based Biomarkers, Treatment and Outcome
Squamous Cell Carcinoma of the Oral Cavity, Squamous Cell Carcinoma of the Oropharynx
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.
Joseph Sacco, MBChB principal investigator
University of Liverpool
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab, Surgery, Radiotherapy and Nivolumab, Surgery, Chemoradiotherapy in people with Squamous Cell Carcinoma of the Oral Cavity, run by The Clatterbridge Cancer Centre NHS Foundation Trust at 1 site in United Kingdom.
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 0 inclusion and 10 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 25 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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?
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?
Disease free survival (time frame: Patients will be followed up for 12 months following surgery). 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 25 Feb 2025.