Study of Nivolumab in Combination With Ipilimumab Compared to the Standard of Care (Extreme Study Regimen) as First Line Treatment in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Phase 1

• Conditions: Recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN); MedDRA version: 20.0Level: 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: EUCTR2016-000725-39-GR
• Lead Sponsor: Bristol-Myers Squibb International Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-07-21
• Last Update Posted: 23 July 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 1329

Inclusion Criteria

a) Histologically confirmed head and neck squamous cell carcinoma (SCCHN), from any of the following primary sites only: oral cavity, oropharynx, hypopharynx and larynx.
b) Must have metastatic or recurrent disease that is not amenable to therapy with curative intent (surgery or radiation therapy with or without chemotherapy). Subjects that refuse potentially curative salvage surgery for recurrent disease are ineligible.
c) No prior treatment with systemic anti-cancer therapy for recurrent or metastatic SCCHN, unless under all of the following conditions:
i) Prior chemotherapy was given as adjuvant or neoadjuvant or as part of multimodal treatment for locally advanced disease
ii) These treatments must have been completed > 6 months prior to enrollment
iii) There is no evidence of disease progression for at least 6 months after completion of such treatment
iv) Subjects having progression after 2 cycles of induction chemotherapy are excluded.
d) ECOG Performance Status of 0-1. (See Appendix 1)
e) Measurable disease by CT or MRI per RECIST 1.1 criteria
f) Documentation of HPV p-16 status is required for SCCHN tumor of the oropharynx.
g) Documentation of PD-L1 status by IHC performed by the central lab prior to randomization.
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 930
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 399

Exclusion Criteria

1. Target Disease Exceptions
a) Recurrent or metastatic carcinoma of the nasopharynx, squamous cell
carcinoma of unknown primary, squamous cell carcinoma that originated
from the skin and salivary gland or non-squamous histologies (eg,
mucosal melanoma).
b) Subjects with untreated CNS metastases. Subjects are eligible if CNS
metastases have been adequately treated and have neurologically
returned to baseline (except for residual signs or symptoms related to
the CNS treatment) for at least 2 weeks prior to randomization. In
addition, subjects must be either off corticosteroids, or on a stable or
decreasing dose of =<10 mg daily prednisone (or equivalent) for at least
2 weeks prior to randomization.
c) Subjects with carcinomatous meningitis.
2. Medical History and Concurrent Diseases
a) Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-
4 antibody, or any other antibody or drug specifically targeting T-cell costimulation
or checkpoint pathways.
b) Prior treatment with cetuximab or EGFR inhibitors in any treatment
setting
c) Subjects with previous malignancies (except non-melanoma skin
cancers, and the following in situ cancers: bladder, gastric, esophageal,
colon, endometrial, cervical/dysplasia, melanoma, or breast) unless a
complete remission was achieved at least 2 years prior to study entry
AND no additional therapy is required during the study period.
i) A second primary squamous cell carcinoma of the head and neck is
allowed if eligibility is based on a recurrent or a metastatic first primary
squamous cell carcinoma of the head and neck.
d) Subjects 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.
e) Subjects 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.
3. Physical and Laboratory Test Findings
a) Any positive test for hepatitis B virus or hepatitis C virus indicating
acute or chronic infection
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b) Known history of testing positive for human immunodeficiency virus
(HIV) or known acquired immunodeficiency syndrome (AIDS).
c) Inadequate hematologic, renal or hepatic function defined by any of
the following screening laboratory values:
i) WBC < 2000/ µl
ii) Neutrophils < 1500/ µl
iii) Platelets < 100 x 1000/µl
iv) Hemoglobin <9.0 g/dL
v) Serum creatinine >1.5 x ULN or creatinine clearance < 50 mL/min
(using the Cockcroft Gault formula). Cisplatin should not be used if
creatinine clearance is lower than 60 mL/min
vi) AST/ALT > 3.0 x ULN (> 5 x ULN if liver metastases)
vii) Total Bilirubin > 1.5 x ULN (except subjects with Gilbert Syndrome
who must have a total bilirubin level >= 3.0 x ULN)

Study & Design

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