CA209-891: Neoadjuvant and Adjuvant Nivolumab as Immune Checkpoint Inhibition in Oral Cavity Cancer

Phase 2

Completed

• Conditions: Squamous Cell Carcinoma of the Oral Cavity
• Interventions: Biological: Nivolumab, Surgery, Radiotherapy; Biological: Nivolumab, Surgery, Chemoradiotherapy

• Registration Number: NCT03721757
• Lead Sponsor: The Clatterbridge Cancer Centre NHS Foundation Trust

Brief 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.

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 Timeline

• Study First Submitted: 2018-07-23
• Study First Submitted QC: 2018-10-25
• Study First Posted: 2018-10-26
• Study Start: 2019-05-10
• Status Verified: 2025-02
• Primary Completion: 2025-02-24
• Study Completion: 2025-02-24
• Last Update Submitted: 2025-02-24
• Last Update Posted: 2025-02-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

Inclusion Criteria

Not provided

Exclusion Criteria

1. Tumours staged as T4 on the basis of bone invasion only and in the absence of nodal metastases.
2. Distant metastases detected, or suspected on imaging
3. Unfit for chemoradiotherapy, due to comorbidity.
4. 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.
5. Prior head and neck radiotherapy
6. On immunosuppressive medication (including steroids at dose equivalent to prednisolone >10mg/day unless used as replacement therapy).
7. 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.
8. Known human immunodeficiency virus (HIV) or viral hepatitis infection.
9. Women who are pregnant or breastfeeding
10. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Nivolumab, Surgery, Radiotherapy	Nivolumab, Surgery, Radiotherapy	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
Nivolumab, Surgery, Chemoradiotherapy	Nivolumab, Surgery, Chemoradiotherapy	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.

Primary Outcome Measures

Name	Time	Method
Recruitment Rate	Period of recruitment	Measured as the number of patients/site/month
Disease free survival	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

Secondary Outcome Measures

Name	Time	Method
Overall survival	Patients will be followed up for 12 months following surgery	Overall survival measured as the time from surgery to death by any cause
Surgical complications - length of hospital admission	up to 8 weeks post date of surgery	Measured as length of time between admission for surgery and discharge
Surgical complications - Infection rate	up to 8 weeks post date of surgery	Measured as incidence of post surgical infection
The change of Quality of Life: EORTC QLQ-C30 v3	Patients will be followed up for 12 months following surgery	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.
Surgical complications - free flap failure	up to 8 weeks post date of surgery	Measured as incidence of failure of free flap reconstruction
The change of symptom	Patients will be followed up for 12 months following surgery	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.
Surgical complications - perioperative (30-day mortality)	up to 30 days post date of surgery	Measured as Incidence of death post surgery by any cause
Assessment of adverse events	Following participants informed consent up to 100 days following last dose of trial treatment.	Assessment of adverse events, adverse events recorded will be classified using CTCAE v4

Trial Locations

Locations (1)

Clatterbridge Cancer Centre NHS Foundation Trust; 🇬🇧 Bebington, United Kingdom