Purpose

This phase II/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 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: Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

- STEP 1: Patients must have oropharynx cancer that is p16-positive by
immunohistochemistry with smoking status: >= 10 pack-years, stage T1-2N2-N3 or
T3-4N0-3 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 or radiation treatment for
p16 positive oropharyngeal squamous cell carcinoma (OPSCC).

- 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 a different malignancy are excluded, unless the
disease has not progressed for >= 2 years.

- 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 1.5 times the normal limits (must be obtained =< 2
weeks prior to randomization).

- STEP 1: Women 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 randomization to rule out pregnancy.

A woman 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: Women of childbearing potential (WOCBP) and males who are sexually active with
WOCBP 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 for women of childbearing
potential and 7 months after the last dose of protocol treatment for males who are
sexually active with WOCBP.

- STEP 1: Patients must have measurable disease as defined.

- 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 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 clearance of >= 60 ml/min (must be obtained =< 2 weeks prior to
registration). Creatinine clearance may be measured or calculated. If calculating,
creatinine clearance, use the Cockcroft-Gault formula.

- 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: Women 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: Women of childbearing potential (WOCBP) and males who are sexually active with
WOCBP 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 for women of childbearing
potential and 7 months after the last dose of protocol treatment for males who are
sexually active with WOCBP.

- STEP 2: Patients must have measurable disease.

- 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.

Study Design

Phase
Phase 2/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.
  • 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
  • Radiation: Intensity-Modulated Radiation Therapy
    Undergo IMRT
    Other names:
    • IMRT
    • Intensity Modulated RT
    • Intensity-Modulated Radiotherapy
    • Radiation, Intensity-Modulated Radiotherapy
  • Biological: Nivolumab
    Given IV
    Other names:
    • BMS-936558
    • MDX-1106
    • NIVO
    • ONO-4538
    • Opdivo
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.
  • 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
  • Radiation: Intensity-Modulated Radiation Therapy
    Undergo IMRT
    Other names:
    • IMRT
    • 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
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.
  • Biological: Nivolumab
    Given IV
    Other names:
    • BMS-936558
    • MDX-1106
    • NIVO
    • ONO-4538
    • Opdivo

Recruiting Locations

Montefiore Medical Center - Moses Campus
Bronx, New York 10467
Contact:
Site Public Contact
718-379-6866
aaraiza@montefiore.org

More Details

Status
Recruiting
Sponsor
National Cancer Institute (NCI)

Study Contact

Detailed Description

PRIMARY OBJECTIVES:

I. To assess the efficacy of concurrent definitive therapy followed by nivolumab compared with concurrent definitive therapy followed by observation in terms of progression-free survival (PFS). (Phase II) II. 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). (Phase III)

SECONDARY OBJECTIVES:

I. The relationship of baseline PD-L1 expression to clinical outcome. II. To evaluate the predictive value of human papillomavirus (HPV)16 E6 and E7 deoxyribonucleic acid (DNA) in saliva and plasma, at baseline, 12 weeks and 9 months after completion of radiation on PFS and OS in both arms of the study.

III. To evaluate the tumor mutation burden by whole exome sequencing of the initial pretreatment tissue sample as well as samples obtained at the time of progression.

IV. To evaluate the association of 12 week post therapy fludeoxyglucose F-18 (FDG) positron emission tomography(PET)/computed tomography (CT) with PFS and OS.

V. 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).

VI. To correlate SUVmax of primary tumor or nodal metastasis of baseline FDG PET/CT with PD-L1 expression (positive vs. negative).

VII. To correlate the post therapy (cisplatin + radiation therapy [RT]) FDG PET/CT with saliva or plasma levels of HPV DNA collected at the time of the standard 3 months PET/CT scan as well as 6 months later (i.e. 9 months post therapy) for both the observation and Nivolumab groups.

VIII. 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.

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.

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.