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A Phase II/III Randomized Study of Maintenance Nivolumab versus Observation in Patients with Locally Advanced, Intermediate Risk HPV Positive OPCA
Cancer Categories
Head and Neck
Karmanos Trial ID
EA3161
NCT ID
NCT03811015
Age Group
Adult
Scope
National
Phase
Phase II
Includes controlled clinical studies conducted to evaluate the effectiveness of the drug for a particular indication or indications in participants with the disease or condition under study and to determine the common short-term side effects and risks.
Phase II/III
Principal Investigator
Ammar
Sukari, M.D.
Oncology - Medical
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Objective:
Primary Objectives:
Phase II: 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 III: 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 the relationship of baseline PD-L1 expression to clinical outcome.
To evaluate the predictive value of HPV16 E6 and E7 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.
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.
To evaluate the association of 12 week post therapy FDG PET/CT with PFS and OS.
To establish the prognostic value of SUVmax of primary tumor or neck nodal metastasis of baseline FDG PET/CT for OS (and/or PFS).
To correlate SUVmax of primary tumor or nodal metastasis of baseline FDG PET/CT with PD-L1 expression (positive vs. negative).
To correlate the post therapy (cisplatin + 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.
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.
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Eligibility
Locations
Applicable Disease Site
Therapies | Drugs | Devices
Eligibility
Eligibility
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
Locations
Locations
Karmanos Cancer Institute - Detroit Headquarters
4100 John R
Detroit, MI 48201
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Phone:
800-527-6266
Karmanos Cancer Institute at McLaren Bay Region
3140 W Campus Dr.
Bay City, MI 48706
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Phone:
989-667-2370
Karmanos Cancer Institute at McLaren Central Michigan, Morey Cancer Center
1221 South Drive
Mount Pleasant, MI 48858
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Phone:
989-772-6811
Karmanos Cancer Institute at McLaren Clarkston
5680 Bow Pointe Dr
Clarkston, MI 48346
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Phone:
248-922-6650
Karmanos Cancer Institute at McLaren Flint
4100 Beecher Rd
Flint, MI 48532
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Phone:
810-342-3800
Karmanos Cancer Institute at McLaren Greater Lansing - Medical Oncology and Hematology
3520 Forest Rd.
Lansing, MI 48910
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Phone:
517-975-9500
Karmanos Cancer Institute at McLaren Lapeer Region
1295 Barry Drive
Lapeer, MI 48446
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Phone:
800-527-6266
Karmanos Cancer Institute at McLaren Macomb
1080 Harrington Blvd
Mount Clemens, MI 48043
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Phone:
586-493-7510
Karmanos Cancer Institute at McLaren Northern Michigan, Petoskey
560 W Mitchell St
Petoskey, MI 49770
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Phone:
231-487-3390
Karmanos Cancer Institute at McLaren Port Huron
1221 Pine Grove Ave
Port Huron, MI 48060
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Phone:
810-982-5200
Karmanos Cancer Institute at Weisberg Cancer Center - Farmington Hills
31995 Northwestern Hwy
Farmington Hills, MI 48334
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Phone:
800-527-6266
Applicable Disease Site
Applicable Disease Site
Lip, Oral Cavity and Pharynx
Therapies, Drugs, Devices
Therapies | Drugs | Devices
Therapies
Chemotherapy, Immunotherapy, Radiation Therapy
Drugs
Cisplatin; Nivolumab
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