Clinical Trials /

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

NCT03721757

Description:

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.

Related Conditions:
  • Oral Cavity Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: CA209-891: Neoadjuvant and Adjuvant Nivolumab as Immune Checkpoint Inhibition in Oral Cavity Cancer
  • Official Title: NICO - CA209-891: Neoadjuvant and Adjuvant Nivolumab as Immune Checkpoint Inhibition in Oral Cavity Cancer

Clinical Trial IDs

  • ORG STUDY ID: C0947
  • SECONDARY ID: 2017-005015-13
  • SECONDARY ID: ISRCTN17428671
  • SECONDARY ID: CA209-891
  • NCT ID: NCT03721757

Conditions

  • Squamous Cell Carcinoma of the Oral Cavity

Interventions

DrugSynonymsArms
Nivolumab, Surgery, RadiotherapyCurative Surgery, Adjuvant RadiotherapyNivolumab, Surgery, Radiotherapy
Nivolumab, Surgery, ChemoradiotherapyCurative surgery, Adjuvant chemoradiotherapyNivolumab, Surgery, Chemoradiotherapy

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Nivolumab, Surgery, RadiotherapyOtherPatients 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, Radiotherapy
Nivolumab, Surgery, ChemoradiotherapyOtherPatients 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.
  • Nivolumab, Surgery, Chemoradiotherapy

Eligibility 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 used consistently and correctly

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Disease free survival
Time Frame:Patients will be followed up for 12 months following surgery
Safety Issue:
Description:1 year disease free survival defined as disease recurrence or death at 12 months from surgery

Secondary Outcome Measures

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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:The Clatterbridge Cancer Centre NHS Foundation Trust

Trial Keywords

  • Head and Neck cancer
  • Squamous cell carcinoma

Last Updated

July 14, 2020