Mouth cancer Cancer Malignant neoplasm of mouth, unspecified
Conditions
Interventions
This is a non-randomised phase II study of nivolumab in high risk oral cavity cancer for whom resection is the primary treatment. Patients will be assigned to one of two cohorts based on pathological
Sponsors
The Clatterbridge Cancer Centre NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed, written informed consent 2. Subjects must be willing and able to comply with scheduled visits and procedures 3. Histologically confirmed squamous cell carcinoma of the oral cavity (oral tongue (anterior 2/3), gingiva/alveolus, floor of mouth, buccal sulcus, retromolar trigone, and hard palate as defined by ICD-10 codes) 4. Subjects willing to have a fresh biopsy performed, or archival tissue available from diagnostic biopsy meeting requirements set out in laboratory manual 5. Clinically and/or radiologically staged as T1-4 N1-3 or any T3-4 N0 (unless T4 on the basis of bone invasion only). Staging based upon the AJCC/UICC TNM 8th Edition 6. Surgery planned as primary treatment modality with patients fit for major resection ± reconstruction surgical procedure 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 8. 18 years or over at time of provision of consent for trial inclusion 9. Screening laboratory values must meet the following criteria: WBC = 2000/µL Neutrophils = 1500/uL Platelets = 100x103/uL Hemoglobin = 9.0 g/dL Serum creatinine =1.5 x ULN or calculated creatinine clearance > 40 mL/min (using the Cockcroft-Gault formula) AST = 3.0 x ULN ALT = 3.0 x ULN Total Bilirubin = 1.5 x ULN (except subjects with Gilbert Syndrome who must have a total bilirubin level of < 3.0x ULN) 10. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug 11. Women must not be breastfeeding 12. WOCBP must agree to follow instructions for method(s) of contraception for a period of 30 days (duration of ovulatory cycle) plus the time required for the investigational drug to undergo approximately five half-lives. WOCBP randomized/assigned to receive nivolumab should use an adequate method to avoid pregnancy for 5 months (30 days plus the time required for nivolumab to undergo approximately five half-lives) after the last dose of investigational drug 13. Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for a period of 90 days (duration of sperm turnover) plus the time required for the investigational drug to undergo approximately five half-lives 14. Males randomized to receive nivolumab who are sexually active with WOCBP must continue contraception for 7 months (90 days plus the time required for nivolumab to undergo approximately five half-lives) after the last dose of investigational drug. Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, they must still undergo pregnancy testing as described in these sections. Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy Investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on the use of highly effective methods of contraception. Highly effective methods of contraception which have a failure rate of < 1% when u
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. 1-year disease free survival = 75% in high-risk population. The endpoint is disease recurrence at 12 months measured as a 1 for patients who have disease recurrence (or death by any cause) and 0 for those that do not 2. Feasibility of recruitment to both cohorts, predominantly assessed using the recruitment rate as the endpoint of interest measured as the number of patients/site/month | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Safety, measured and categorised based on CTCAE (version 4). Interest will predominantly be on the number of grade 3/4 adverse events 2. Time to recurrence, measured as the time from surgery until disease recurrence or death by any cause 3. Overall survival, measured as the time from registration until death by any cause 4. Quality of life, measured using Quality of Life Questionnaire–Core 30 module (QLQ-C30) and the head-and-neck–specific module (QLQ-H&N35) at: 4.1. Prior to surgery and initial nivolumab treatment 4.2. Post surgery but pre-radiotherapy/chemoradiotherapy 4.3. First administration of nivolumab post radiotherapy/chemoradiotherapy 4.4. Third administration of nivolumab post radiotherapy/chemoradiotherapy 4.5. Sixth administration of nivolumab post radiotherapy/chemoradiotherapy 4.6. End of study treatment/safety visit 5. Surgical complications: infection rate, length of hospital admission, free flap failure, perioperative (30-day) mortality | — |
Countries
United Kingdom
Outcome results
None listed