A Phase 3 Study of Nivolumab or Nivolumab plus Cisplatin, in Combination with Radiotherapy in Patients with Advanced Cancer of the Head and Neck

Phase 1

• Conditions: MedDRA version: 20.0 Level: PT Classification code 10060121 Term: Squamous cell carcinoma of head and neck System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-002676-87-ES
• Lead Sponsor: Bristol-Myers Squibb International Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-01-04
• Last Update Posted: 1 February 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 1046

Inclusion Criteria

• Histologically proven SCCHN from one of the following primary sites: oral cavity, oropharynx, hypopharynx, and larynx
• Locally advanced disease which is un-resectable, or resectable but suitable for an organ sparing approach
• No previous radiotherapy or systemic treatment for SCCHN
• Eastern cooperative oncology group (ECOG) score of 0-1
• Age > 18 years or age of majority
• Measurable disease by RECIST 1.1 criteria, and tumor assessment performed prior to randomization
• Sufficient sample of fresh or archival (< 3 months from informed consent date) formalin-fixed, paraffin-embedded (FFPE) tissue block, or unstained tumor tissue sections, with an associated pathology report, must be submitted for biomarker evaluation for PD-L1 status. Central lab must provide Interactive Response Technology (IRT) with confirmation of receipt of evaluable tumor tissue prior to randomization. Biopsy should be excisional, incisional or core needle. Fine needle or aspiration is unacceptable for submission. PD-L1 status must be available prior to randomization.
• HPV p16 test result available (performed locally or centrally) for participants with oropharyngeal disease
•Patients must be of intermediate or high risk categories*:
• High risk:
• Oral cavity, hypopharynx, larynx, oropharynx (p16 negative): Stage III/ IV
• Oropharynx (p16 positive): Stage III (T4 any N or T1-3 N3) - irrespective of smoking status.
• Intermediate risk:
• Oropharynx (p16 positive): T3 N0-2or T1-3 N2 disease if smoking > 20 pack year history
*TNM staging according to AJCC version 8

Cohort 1 (cisplatin-ineligible participants) Specific Inclusion Criteria (Arm A and Arm B)
• Physician assesses participant to be non-eligible for treatment with platinum based combined CRT. This must be for one or more of the following reasons:
• Age = 70 years at enrolment
• Creatinine clearance < 60mL/min and > 30mL/min (using the Cockcroft and Gault formula– see below**)
• Severe hearing loss (minimal hearing threshold of 80 dB or more in either ear)
Cohort 2 (cisplatin-eligible participants) Specific Inclusion Criteria (Arm C and Arm D)
• Adequate renal function within 28 days prior to randomization as follows:
• Creatinine clearance = 60 mL/min. as determined by 24 hour collection or estimated by Cockcroft-Gault formula:
Creatinine Clearance = [(140 - age) x (wt in kg)/Serum Cr mg/dL x 72**

**Participants aged = 70 years may enter either Cohort 1 or 2 dependent on whether the physician’s assessment is that
the participant is eligible for cisplatin (Cohort 2) or ineligible for cisplatin (Cohort 1) based on their age. It is anticipated that in the majority of cases, patients aged = 70 years will be considered ineligible for cisplatin and enter cohort 1.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 291
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 755

Exclusion Criteria

• Carcinoma originating in the nasopharynx or paranasal sinus, squamous cell carcinoma that originated from the skin and salivary gland or non-squamous histology (eg, mucosal melanoma), squamous cell carcinoma of unknown primary
• Clinical or radiological evidence of metastatic disease
• Prior radiotherapy that overlaps with radiation fields
• Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the participant to receive protocol therapy, or interfere with the interpretation of study results
• Active unstable angina and/or congestive heart failure
• Myocardial infarction within 6 months prior to randomization
• Participants who have a weight loss of > 10% of body weight between screening and randomization will be removed from the study
• Participants with an active, known or suspected autoimmune disease. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Participants with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified