Purpose

This phase III trials studies whether maintenance immunotherapy (nivolumab) following definitive treatment with radiation and chemotherapy (cisplatin) result in significant improvement in overall survival (time being alive) and progression-free survival (time being alive without cancer) for patients with intermediate risk human papillomavirus (HPV) positive oropharynx cancer (throat cancer) that has spread to nearby tissue or lymph nodes. Drugs used in chemotherapy such as cisplatin work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether chemotherapy and radiation therapy followed by maintenance nivolumab therapy works better than chemotherapy and radiation therapy alone in treating patients with HPV positive oropharyngeal cancer.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Criteria


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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Crossover Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Arm A (cisplatin, IMRT, nivolumab)
Patients receive cisplatin IV over 60 minutes weekly and IMRT 5 days a week for 7 weeks for a total of 35 fractions. Within 4 weeks after completion of concurrent therapy, patients receive nivolumab IV once weekly over 30 minutes every 4 weeks for 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo CT or FDG PET/CT scans throughout the trial. Patients may undergo ECHO as clinically indicated. Additionally, patients undergo blood sample collection during screening.
  • Procedure: Biospecimen Collection
    Undergo blood sample collection
    Other names:
    • Biological Sample Collection
    • Biospecimen Collected
    • Specimen Collection
  • Drug: Cisplatin
    Given IV
    Other names:
    • Abiplatin
    • Blastolem
    • Briplatin
    • CDDP
    • Cis-diammine-dichloroplatinum
    • Cis-diamminedichloridoplatinum
    • Cis-diamminedichloro Platinum (II)
    • Cis-diamminedichloroplatinum
    • Cis-dichloroammine Platinum (II)
    • Cis-platinous Diamine Dichloride
    • Cis-platinum
    • Cis-platinum II
    • Cis-platinum II Diamine Dichloride
    • Cismaplat
    • Cisplatina
    • Cisplatinum
    • Cisplatyl
    • Citoplatino
    • Citosin
    • Cysplatyna
    • DDP
    • Lederplatin
    • Metaplatin
    • Neoplatin
    • Peyrone's Chloride
    • Peyrone's Salt
    • Placis
    • Plastistil
    • Platamine
    • Platiblastin
    • Platiblastin-S
    • Platinex
    • Platinol
    • Platinol- AQ
    • Platinol-AQ
    • Platinol-AQ VHA Plus
    • Platinoxan
    • Platinum
    • Platinum Diamminodichloride
    • Platiran
    • Platistin
    • Platosin
  • Procedure: Computed Tomography
    Undergo CT or PET/CT
    Other names:
    • CAT
    • CAT Scan
    • Computed Axial Tomography
    • Computerized Axial Tomography
    • Computerized axial tomography (procedure)
    • Computerized Tomography
    • Computerized Tomography (CT) scan
    • CT
    • CT Scan
    • tomography
  • Procedure: Echocardiography
    Undergo ECHO
    Other names:
    • EC
  • Other: Fludeoxyglucose F-18
    Receive FDG
    Other names:
    • 18FDG
    • FDG
    • Fludeoxyglucose (18F)
    • fludeoxyglucose F 18
    • Fludeoxyglucose F18
    • Fluorine-18 2-Fluoro-2-deoxy-D-Glucose
    • Fluorodeoxyglucose F18
  • Radiation: Intensity-Modulated Radiation Therapy
    Undergo IMRT
    Other names:
    • IMRT
    • Intensity modulated radiation therapy (procedure)
    • Intensity Modulated RT
    • Intensity-Modulated Radiotherapy
    • Radiation, Intensity-Modulated Radiotherapy
  • Biological: Nivolumab
    Given IV
    Other names:
    • ABP 206
    • BCD-263
    • BMS-936558
    • CMAB819
    • MDX-1106
    • NIVO
    • Nivolumab Biosimilar ABP 206
    • Nivolumab Biosimilar BCD-263
    • Nivolumab Biosimilar CMAB819
    • ONO-4538
    • Opdivo
  • Procedure: Positron Emission Tomography
    Undergo PET/CT
    Other names:
    • Medical Imaging, Positron Emission Tomography
    • PET
    • PET Scan
    • Positron emission tomography (procedure)
    • Positron Emission Tomography Scan
    • Positron-Emission Tomography
    • proton magnetic resonance spectroscopic imaging
    • PT
Active Comparator
Arm B (cisplatin, IMRT, observation)
Patients receive cisplatin IV over 60 minutes weekly and IMRT 5 days a week for 7 weeks for a total of 35 fractions, and then go on observation. Patients will be offered the option to cross-over to Arm C if they have clearly documented progression within 12 months from the end of cisplatin/radiation therapy. Patients undergo CT or FDG PET/CT scans throughout the trial. Patients may undergo ECHO as clinically indicated. Additionally, patients undergo blood sample collection during screening.
  • Procedure: Biospecimen Collection
    Undergo blood sample collection
    Other names:
    • Biological Sample Collection
    • Biospecimen Collected
    • Specimen Collection
  • Drug: Cisplatin
    Given IV
    Other names:
    • Abiplatin
    • Blastolem
    • Briplatin
    • CDDP
    • Cis-diammine-dichloroplatinum
    • Cis-diamminedichloridoplatinum
    • Cis-diamminedichloro Platinum (II)
    • Cis-diamminedichloroplatinum
    • Cis-dichloroammine Platinum (II)
    • Cis-platinous Diamine Dichloride
    • Cis-platinum
    • Cis-platinum II
    • Cis-platinum II Diamine Dichloride
    • Cismaplat
    • Cisplatina
    • Cisplatinum
    • Cisplatyl
    • Citoplatino
    • Citosin
    • Cysplatyna
    • DDP
    • Lederplatin
    • Metaplatin
    • Neoplatin
    • Peyrone's Chloride
    • Peyrone's Salt
    • Placis
    • Plastistil
    • Platamine
    • Platiblastin
    • Platiblastin-S
    • Platinex
    • Platinol
    • Platinol- AQ
    • Platinol-AQ
    • Platinol-AQ VHA Plus
    • Platinoxan
    • Platinum
    • Platinum Diamminodichloride
    • Platiran
    • Platistin
    • Platosin
  • Procedure: Computed Tomography
    Undergo CT or PET/CT
    Other names:
    • CAT
    • CAT Scan
    • Computed Axial Tomography
    • Computerized Axial Tomography
    • Computerized axial tomography (procedure)
    • Computerized Tomography
    • Computerized Tomography (CT) scan
    • CT
    • CT Scan
    • tomography
  • Procedure: Echocardiography
    Undergo ECHO
    Other names:
    • EC
  • Other: Fludeoxyglucose F-18
    Receive FDG
    Other names:
    • 18FDG
    • FDG
    • Fludeoxyglucose (18F)
    • fludeoxyglucose F 18
    • Fludeoxyglucose F18
    • Fluorine-18 2-Fluoro-2-deoxy-D-Glucose
    • Fluorodeoxyglucose F18
  • Radiation: Intensity-Modulated Radiation Therapy
    Undergo IMRT
    Other names:
    • IMRT
    • Intensity modulated radiation therapy (procedure)
    • Intensity Modulated RT
    • Intensity-Modulated Radiotherapy
    • Radiation, Intensity-Modulated Radiotherapy
  • Other: Patient Observation
    Undergo observation
    Other names:
    • Active Surveillance
    • deferred therapy
    • expectant management
    • Observation
    • Watchful Waiting
  • Procedure: Positron Emission Tomography
    Undergo PET/CT
    Other names:
    • Medical Imaging, Positron Emission Tomography
    • PET
    • PET Scan
    • Positron emission tomography (procedure)
    • Positron Emission Tomography Scan
    • Positron-Emission Tomography
    • proton magnetic resonance spectroscopic imaging
    • PT
Experimental
Arm C (nivolumab)
Patients receive nivolumab IV over 30 minutes every 4 weeks for 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo CT or FDG PET/CT scans throughout the trial. Patients may undergo ECHO as clinically indicated. Additionally, patients undergo blood sample collection during screening.
  • Procedure: Biospecimen Collection
    Undergo blood sample collection
    Other names:
    • Biological Sample Collection
    • Biospecimen Collected
    • Specimen Collection
  • Procedure: Computed Tomography
    Undergo CT or PET/CT
    Other names:
    • CAT
    • CAT Scan
    • Computed Axial Tomography
    • Computerized Axial Tomography
    • Computerized axial tomography (procedure)
    • Computerized Tomography
    • Computerized Tomography (CT) scan
    • CT
    • CT Scan
    • tomography
  • Procedure: Echocardiography
    Undergo ECHO
    Other names:
    • EC
  • Other: Fludeoxyglucose F-18
    Receive FDG
    Other names:
    • 18FDG
    • FDG
    • Fludeoxyglucose (18F)
    • fludeoxyglucose F 18
    • Fludeoxyglucose F18
    • Fluorine-18 2-Fluoro-2-deoxy-D-Glucose
    • Fluorodeoxyglucose F18
  • Biological: Nivolumab
    Given IV
    Other names:
    • ABP 206
    • BCD-263
    • BMS-936558
    • CMAB819
    • MDX-1106
    • NIVO
    • Nivolumab Biosimilar ABP 206
    • Nivolumab Biosimilar BCD-263
    • Nivolumab Biosimilar CMAB819
    • ONO-4538
    • Opdivo
  • Procedure: Positron Emission Tomography
    Undergo PET/CT
    Other names:
    • Medical Imaging, Positron Emission Tomography
    • PET
    • PET Scan
    • Positron emission tomography (procedure)
    • Positron Emission Tomography Scan
    • Positron-Emission Tomography
    • proton magnetic resonance spectroscopic imaging
    • PT

Recruiting Locations

Memorial Hermann Texas Medical Center
Houston, Texas 77030
Contact:
Site Public Contact
713-792-3245

Memorial Hermann Northeast Hospital
Humble, Texas 77338
Contact:
Site Public Contact
ecog.rss@jimmy.harvard.edu

More Details

Status
Recruiting
Sponsor
National Cancer Institute (NCI)

Study Contact

Detailed Description

PRIMARY OBJECTIVE: I. 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: I. To further assess the efficacy of nivolumab compared with observation in terms of: Ia. To evaluate treatment effect within the subset of patients tested as PD-L1+ . Ib. To evaluate the prognostic effect of baseline saliva and/or plasma HPV status . Ic. To evaluate the prognostic effect of mutation burden among patients on the nivolumab arm. Id. To evaluate the association of 12-week post therapy fludeoxyglucose F-18 (FDG) positron emission tomography(PET)/computed tomography (CT) OS and progression free survival (PFS). Ie. To establish the prognostic value of standardized uptake value (SUV) max of primary tumor or neck nodal metastasis of baseline FDG PET/CT for OS (and/or PFS). If. To correlate SUV max of primary tumor or nodal metastasis of baseline FDG PET/CT with PD-L1 expression (positive versus [vs.] negative). Ig. To compare the PET based therapy response assessment (Hopkins criteria) to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessment at 12 week post chemoradiation therapy, for patients who have a PET/CT scan at 12 weeks. II. To assess the efficacy of concurrent definitive therapy followed by nivolumab in terms of progression free survival (PFS). OUTLINE: Patients are randomized to Arm A or Arm B. Patients in Arm B may cross-over to Arm C with clearly documented disease progression. ARM A: Patients receive cisplatin intravenously (IV) over 60 minutes weekly and intensity modulated radiation therapy (IMRT) 5 days a week for 7 weeks for a total of 35 fractions. Within 4 weeks after completion of concurrent therapy, patients receive nivolumab IV once weekly over 30 minutes every 4 weeks for 12 months in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive cisplatin IV over 60 minutes weekly and IMRT 5 days a week for 7 weeks for a total of 35 fractions, and then go on observation. Patients will be offered the option to cross-over to Arm C if they have clearly documented progression within 12 months from the end of cisplatin/radiation therapy. ARM C: Patients receive nivolumab IV over 30 minutes every 4 weeks for 12 months in the absence of disease progression or unacceptable toxicity. All patients undergo computed tomography (CT) or Fludeoxyglucose F-18 (FDG) positron emission tomography (PET)/CT scans throughout the trial. Patients may undergo echocardiography (ECHO) as clinically indicated. Additionally, patients undergo blood sample collection during screening. After completion of study treatment, patients are followed up every 3-6 months for 3 years and then annually for a total of 10 years.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.