A Phase III Randomized Study of Maintenance Nivolumab versus Observation in Patients with Locally Advanced, Intermediate Risk HPV Positive OPSCC.
Primary Objectives:
To assess the efficacy of concurrent definitive therapy followed by nivolumab compared with concurrent definitive therapy followed by observation in terms of overall survival (OS).
Secondary Objectives:
- To further assess the efficacy of nivolumab compared with observation in terms of:
- To evaluate treatment effect within the subset of patients tested as PD-L1+
- To evaluate the prognostic effect of baseline saliva and/or plasma HPV status
- To evaluate the prognostic effect of mutation burden among patients on the Nivolumab arm
- To evaluate the association of 12-week post therapy FDG PET/CT OS and PFS.
- To establish the prognostic value of SUV max of primary tumor or neck nodal metastasis of baseline FDG PET/CT for OS (and/or PFS).
- To correlate SUV max of primary tumor or nodal metastasis of baseline FDG PET/CT with PD- L1 expression (positive vs. negative).
- To compare the PET based therapy response assessment (Hopkins criteria) to the RECIST 1.1 assessment at 12 week post chemoradiation therapy, for patients who have a PET/CT scan at 12 weeks.
CISPLATIN
- Rutgers Cancer Institute of New Jersey
- Principal Investigator
- Missak Haigentz MD
- Principal Investigator
- RWJBarnabas Health
- Cooperman Barnabas, Livingston
- Jersey City Medical Center, Jersey City
- Rutgers Cancer Institute of New Jersey-University Hospital
Inclusion Criteria
- STEP 1: Age >= 18 years
- STEP 1: Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- STEP 1: Patients must have oropharynx cancer (American Joint Committee on Cancer
[AJCC] 8) that is p16-positive by immunohistochemistry OR p16 equivocal by IHC and HPV
positive by in situ hybridization with the following criteria: >= 10 pack-years, stage
T1-2N2-N3 or T3-4N0-3 (less than 10 pack-years is considered a non-smoker) OR < 10
pack-years, stage T4N0-N3 or T1-3N2-3
- STEP 1: Patients must not have known hypersensitivity to nivolumab or compounds of
similar chemical or biologic composition.
- STEP 1: Patients with a history of allergic reactions attributed to platinum-based
chemotherapy agents are excluded.
- STEP 1: Patients must not have had prior systemic therapy, radiation treatment or
surgery for p16 positive oropharyngeal squamous cell carcinoma (OPSCC).
- NOTE: Patients who had resection of T1 or T2 carcinoma with no radiation or
chemotherapy are eligible if surgery was done 5 years prior to enrollment
- STEP 1: Patients must not have received previous irradiation for head and neck tumor,
skull base, or brain tumors.
- STEP 1: Patients must not receive investigational agents within 4 weeks of enrollment
or at any time while on study.
- STEP 1: Patients with evidence of distant metastases or leptomeningeal disease (LMD)
are excluded.
- STEP 1: Patients with uncontrolled inter-current illnesses which in the opinion of the
investigator will interfere with the ability to undergo therapy including chemotherapy
are excluded.
- STEP 1: Patients with a history of prior or second malignancy are excluded, with the
exception of curatively treated non-melanoma skin cancer, or curatively treated
cervical cancer; additionally, patients curatively treated for malignancy who remain
disease-free at > 2 years of follow up, are not excluded.
- STEP 1: Absolute neutrophil count (ANC) >= 1500/mm^3 (must be obtained =< 2 weeks
prior to randomization).
- STEP 1: Hemoglobin (Hgb) >= 8.0 g/dL (must be obtained =< 2 weeks prior to
randomization).
- STEP 1: Platelet count >= 100,000/mm^3 (must be obtained =< 2 weeks prior to
randomization).
- STEP 1: Creatinine clearance of >= 60 ml/min (must be obtained =< 2 weeks prior to
randomization). Creatinine clearance may be measured or calculated. If calculating,
creatinine clearance, use the Cockcroft-Gault formula.
- STEP 1: Total bilirubin within 1.5 times the normal limits (must be obtained =< 2
weeks prior to randomization).
- STEP 1: Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase
[AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase
[ALT]) within 2.0 times the normal limits (must be obtained =< 2 weeks prior to
randomization).
- STEP 1: Alkaline phosphatase within 2.0 times the normal limits (must be obtained =< 2
weeks prior to randomization).
- STEP 1: Patients must not be pregnant or breast-feeding as chemotherapy, radiation,
and immunotherapy may have possible teratogenicity effects; in addition, complications
from pregnancy may interfere with the ability of patients to have an uninterrupted
therapy. All patients of childbearing potential must have a blood test or urine study
within 2 weeks prior to randomization to rule out pregnancy. A patient of childbearing
potential is any female, regardless of sexual orientation or whether they have
undergone tubal ligation, who meets the following criteria: 1) has achieved menarche
at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has
not been naturally postmenopausal (amenorrhea following cancer therapy does not rule
out childbearing potential) for at least 24 consecutive months (i.e., has had menses
at any time in the preceding 24 consecutive months).
- STEP 1: Patients of childbearing potential must use an accepted and effective method
of contraception or abstain from sexual intercourse for at least one week prior to the
start of treatment, and continue for 5 months after the last dose of protocol
treatment. Patients must also not donate ova during this same time period.
- STEP 1: Patients must have measurable disease
- STEP 1: Patients must have tumor measurements with CT of neck and CT of chest (or CT
of neck and FDG PET/CT if standard of care) within 4 weeks prior to Step 1
randomization.
- STEP 1: Patients with active autoimmune disease or history of autoimmune disease that
might recur, which may affect vital organ function or require immune suppressive
treatment including systemic corticosteroids, should be excluded. These include but
are not limited to patients with a history of immune related neurologic disease,
multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome,
myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus
(SLE), connective tissue disease, scleroderma, inflammatory bowel disease (IBD),
Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal
necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be
excluded because of the risk of recurrence or exacerbation of disease. Patients with
vitiligo, endocrine deficiencies including thyroiditis managed with replacement
hormones including physiologic corticosteroids are eligible. Patients with rheumatoid
arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with
topical medication and patients with positive serology, such as antinuclear antibodies
(ANA), anti-thyroid antibodies should be evaluated for the presence of target organ
involvement and potential need for systemic treatment but should otherwise be
eligible.
- STEP 1: Patients are permitted to enroll if they have 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 (precipitating event).
- STEP 1: Patients must not have a condition requiring systemic treatment with either
corticosteroids (> 10 mg/day prednisone equivalents) or other immunosuppressive
medications which are expected to continue during nivolumab administration. Inhaled or
topical steroids and adrenal replacement doses > 10 mg/day prednisone equivalents are
permitted in the absence of active autoimmune disease
- STEP 1: Patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV
viral load must be undetectable on suppressive therapy, if indicated
- STEP 1: Patients with a history of hepatitis C virus (HCV) infection must have been
treated and cured. For patients with HCV infection who are currently on treatment,
they are eligible if they have an undetectable HCV viral load
- STEP 1: Patients with a known history of testing positive for human immunodeficiency
virus (HIV) or known acquired immunodeficiency syndrome (AIDS) must have no detectable
viral load on a stable antiviral regimen
- STEP 1: Patients must not be receiving any other investigational agents.
- STEP 1: Patient must not have a baseline clinically significant hearing loss, which in
the opinion of the investigator would preclude the use of cisplatin
- STEP 2: Patients must have progression per RECIST criteria AND tissue-proven
progression on Arm B treatment within 12 months after completion of radiation therapy.
- STEP 2: ECOG performance status of 0 or 1.
- STEP 2: Patients must not have known hypersensitivity to nivolumab or compounds of
similar chemical or biologic composition.
- STEP 2: Patients must not have received non-protocol anti-cancer therapy after
completion of radiation and chemotherapy.
- STEP 2: ANC >= 1500/mm^3 (must be obtained =< 2 weeks prior to registration).
- STEP 2: Hgb >= 8.0 g/dL (must be obtained =< 2 weeks prior to registration).
- STEP 2: Platelet count >= 100,000/mm^3 (must be obtained =< 2 weeks prior to
registration).
- STEP 2: Creatinine within institutional limits of normal (must be obtained =< 2 weeks
prior to registration)
- STEP 2: Total bilirubin within 1.5 times the normal limits (must be obtained =< 2
weeks prior to registration).
- STEP 2: SGOT (AST) or SGPT (ALT) within 2.0 times the normal limits (must be obtained
=< 2 weeks prior to registration).
- STEP 2: Alkaline phosphatase within 1.5 times the normal limits (must be obtained =< 2
weeks prior to registration).
- STEP 2: Patients must not be pregnant or breast-feeding as chemotherapy, radiation,
and immunotherapy may have possible teratogenicity effects; in addition, complications
from pregnancy may interfere with the ability of patients to have an uninterrupted
therapy. All women of childbearing potential must have a blood test or urine study
within 2 weeks prior to registration to rule out pregnancy. A women of childbearing
potential is any female, regardless of sexual orientation or whether they have
undergone tubal ligation, who meets the following criteria: 1) has achieved menarche
at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has
not been naturally postmenopausal (amenorrhea following cancer therapy does not rule
out childbearing potential) for at least 24 consecutive months (i.e., has had menses
at any time in the preceding 24 consecutive months).
- STEP 2: Patients of childbearing potential must use an accepted and effective method
of contraception or abstain from sexual intercourse for at least one week prior to the
start of treatment, and continue for 5 months after the last dose of protocol
treatment. Patients must also not donate ova during this same time period.
- STEP 2: Patients must have measurable disease at the time of documented progression
- NOTE: For patients that have undergone salvage surgery for disease recurrence,
measurable disease is not required at the time of registration to Step 2
- STEP 2: Patients must have tumor measurements with CT of neck and CT of chest (or CT
of neck and FDG PET/CT if standard of care) within 4 weeks prior to Step 2
registration
- NOTE: Patients that have undergone salvage surgery for disease recurrence prior
to Step 2 are not required to have measurable disease post-resection, but must
have CT of neck and CT of chest (or CT of neck and FDG PET/CT if standard of
care) after salvage surgery and within 4 weeks prior to step 2 registration to
establish a baseline prior to nivolumab
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site ClinicalTrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
For further information about clinical trials, please contact us at 732-235-7356.