Screening Trial of Nivolumab With Image Guided, Stereotactic Body Radiotherapy (SBRT) Versus Nivolumab Alone in Patients With Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)

Inclusion Criteria

• Signed Written Informed Consent
• Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines.
• Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other study obligations.
• Target Population
• Males and females ≥ 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Histologically confirmed metastatic HNSCC, including nasopharynx WHO Type I-III histologies; patients can have simultaneous loco-regional disease. Central biopsy review at MSKCC is not required.
• Subjects must have at least two lesions:
• At least one lesion must be safely amenable to irradiation and likely to meet criteria delineated in Section 9.2.1 in the judgment of the treating radiation oncologist. This can be a lesion that was previously irradiated as long as prior radiation was at least 6 months prior to projected first fraction of SBRT and as long as reirradiation dose constraints as outlined in appendix are being met.
• A separate, not-to-be-irradiated lesion measurable by CT or MRI per RECIST 1.1 criteria.
• A formalin fixed, paraffin-embedded (FFPE) tumor tissue block or a minimum of 3 unstained slides of tumor sample obtained via excisional, incisional, or core needle biopsy from a metastatic or loco-regionally recurrent lesion. A new baseline biopsy does not need to be obtained for study purposes. If 3 unstained are unavailable from a metastatic or loco-regionally recurrent lesion, with permission of the PI, FFPE tumor tissue from the primary disease site at the time of original diagnosis is acceptable.
• For oropharynx or nasopharynx primary lesions, documentation of viral status is required (e.g. high risk HPV sub-type PCR, p16 IHC, HPV ISH, EBER, etc). Tests done on primary tumor specimens from date of initial diagnosis at outside institutions are sufficient to meet this criterion
• Prior palliative or curative radiotherapy must be completed at least 14 days prior to randomization.
• Immunosuppressive doses of systemic medication, such as steroids or absorbed topical steroids (doses >10mg/day prednisone or equivalent) must be discontinued at least 14 days prior to Nivolumab administration.
• Screening laboratory values must meet the following criteria (using CTCAE v4.0) and should be obtained within 28 days prior to randomization:
• WBC ≥ 2 K/microliter
• Neutrophils ≥ 1.5 ;K/microliter
• Platelets ≥ 100 K/microliter
• Hemoglobin ≥ 9.0 g/deciliter
• Serum Creatinine ≤ 1.5 x ULN or creatinine clearance > 40ml/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
• AST/ALT ≤ 3 x ULN
• Total bilirubin =92% at rest.
• Reproductive Status
• Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 28 days prior to randomization.
• Women must not be breastfeeding
• Women of childbearing potential must agree to follow instructions for method(s) of contraception from time of enrollment for the duration of treatment with Nivolumab plus 5 half- lives plus 30 days for a total of 23 weeks post treatment completion.
• Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving Nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product.
• Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception.
• Azoospermic males and women of childbearing potential who are continuously not heterosexually active are exempt from contraceptive requirements. How