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: Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN); MedDRA version: 21.0Level: PTClassification code 10060121Term: Squamous cell carcinoma of head and neckSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-002676-87-IT
• Lead Sponsor: BRISTOL-MYERS SQUIBB INTERNATIONAL CORPORATIO

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Completion: 2019-10-14
• Study Start: 2020-11-04
• Last Update Posted: 9 November 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 111

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 N0-2 or T1-3 N2 disease if smoking >
20 pack year history
*TNM clinical 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.
• Participants with active interstitial lung disease (ILD) / pneumonitis or with a history of ILD /pneumonitis requiring steroids.

Study & Design

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