An Open Label, Randomized Phase 3 Clinical Trial of Nivolumab vs Therapy of Investigator's Choice in Recurrent or Metastatic Platinum-refractory Squamous Cell Carcinoma of the Head and Neck (SCCHN)
- Conditions
- Squamous Cell Carcinoma of Head and Neck regionHNSCC
- Registration Number
- NL-OMON44380
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 9
Inclusion Criteria;1. Signed Written Informed Consent
a) Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care.
b) Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study.;2. Target Population
a) Histologically confirmed recurrent or metastatic SCCHN (oral cavity, pharynx, larynx), stage III/IV and not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy).
b) Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (Refer to Appendix 1).
c) Documentation of p16-positive or p16-negative disease to determine human papillomavirus (HPV) status of tumor for NSCC of the oropharynx.
d) Tumor progression or recurrence within 6 months of last dose of platinum therapy in the adjuvant (ie with radiation after surgery), primary (i.e., with radiation), recurrent, or metastatic setting. Clinical progression after platinum therapy is an allowable event for entry and is defined as progression of a lesion at least 10 mm in size that is amenable to caliper measurement (e.g. superficial skin lesion as per RECIST 1.1) or a lesion that has been visualized and photographically recorded with measurements and shown to have progressed.
e) Measurable disease by CT or MRI per RECIST 1.1 criteria (Appendix 3).
f) Tumor tissue (archival or fresh biopsy specimen) must be available for PD-L1 expression analysis and other biomarker correlative studies. For subjects where a fresh biopsy is not feasible, archival tumor material must be made available. The subject must not have received systemic therapy subsequent to obtaining the archived biopsy and prior to screening. Tumor tissue must have been obtained in the metastatic setting or from an unresectable site of disease. For more details, see Section 5.7.3
g) Prior curative radiation therapy must have been completed at least 4 weeks prior to study drug administration. Prior focal palliative radiotherapy must have been completed at least 2 weeks before study drug administration.
h) Immunosuppressive doses of systemic medication, such as steroids or absorbed topical steroids (doses > 10 mg/day prednisone or equivalent) must be discontinued at least 2 weeks before study drug administration.
i) Screening laboratory values must meet the following criteria (using CTCAE v4) and should be obtained within 14 days prior to randomization:
i) WBC >=2000/µL
ii) Neutrophils >= 1500/µL
iii) Platelets >= 100 x103/µL
iv) Hemoglobin >= 9.0 g/dL
v) Serum creatinine >= 1.5 x ULN or creatinine clearance (CrCl) > 40 mL/min (using the Cockcroft-Gault formula): Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL
vi) AST/ALT <= 3 x ULN
vii)Total Bilirubin <= 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL).
viii) Calcium levels must be normalized and maintained within normal limits for study entry and on treatment. Medical management of calcium levels is permitted.
ix) Subjects with an initial magnesium < 0.5 mmol/L (1.2 mg/dL) may receive corr
Exclusion Criteria;1. Target Disease Exceptions
a) Active brain metastases or leptomeningeal metastases are not allowed. Subjects with brain metastases are eligible if these have been treated and there is no magnetic resonance imaging (except where contraindicated in which CT scan is acceptable) evidence of progression for at least 8 weeks after treatment is complete and within 28 days prior to first dose of study drug administration. Cases, including base of skull lesions without definitive evidence of dural or brain parenchymal involvement, should be discussed with the medical monitor. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration.
b) Histologically confirmed recurrent or metastatic carcinoma of the nasopharynx and salivary gland or non-squamous histologies (e.g. mucosal melanoma) are not allowed.;2. Medical History and Concurrent Diseases
a) 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 subject to receive protocol therapy, or interfere with the interpretation of study results.
b) Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
c) Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
d) Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
e) 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 co-stimulation or immune checkpoint pathways.
f) All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have resolved to Grade 1 (NCI CTCAE version 4) or baseline before administration of study drug. Subjects with toxicities attributed to prior anti-cancer therapy which are not expected to resolve and result in long lasting sequelae, such as neuropathy after platinum based therapy, are permitted to enroll.
g) Treatment with any chemotherapy, radiation therapy, biologics for cancer, or investigational therapy within 28 days of first administration of study treatment (subjects with prior cytotoxic or investigational products < 4 weeks prior to treatment might be eligible after discussion between investigator and sponsor, if toxicities from the prior treatment have been resolved to Grade 1 (NCI CTCAE version 4).;3. Physical and Laboratory Test Findings
a) Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.
b) Kno
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To compare PFS and OS of Nivolumab to Investigator*s Choice in subjects who<br /><br>have tumor progression within 6 months of last dose of platinum therapy in the<br /><br>primary, recurrent, or metastatic setting.</p><br>
- Secondary Outcome Measures
Name Time Method