Testing Immunotherapy Versus Observation in Patients With HPV Throat Cancer

  • STATUS
    Recruiting
  • End date
    Jan 1, 2027
  • participants needed
    744
  • sponsor
    National Cancer Institute (NCI)
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Updated on 20 January 2021
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Summary

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 (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.

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. To further assess the efficacy of nivolumab compared with observation in terms of:

Ia. The relationship of baseline PD-L1 expression to clinical outcome. Ib. To evaluate the association of 12 week post therapy fludeoxyglucose F-18 (FDG) positron emission tomography(PET)/computed tomography (CT) with PFS and OS.

Ic. 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).

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

Ie. 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.

Details
Treatment cisplatin, Nivolumab, intensity-modulated radiation therapy, Patient Observation
Clinical Study IdentifierNCT03811015
SponsorNational Cancer Institute (NCI)
Last Modified on20 January 2021

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Eligibility

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Inclusion Criteria

Do you have any of these conditions: Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 or Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinom...?
Do you have any of these conditions: Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 or Human Papillomavirus-16 Positive or Pathologic Stage II HPV-Mediated ...?
Do you have any of these conditions: Human Papillomavirus-16 Positive or Pathologic Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 or Pathologic Stage II HPV-Mediat...?
Do you have any of these conditions: Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 or Human Papillomavirus-16 Positive or smoker or Clinical Stage III HPV-...?
Do you have any of these conditions: Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 or smoker or Human Papillomavirus-16 Positive or Pathologic Stage II HP...?
Do you have any of these conditions: smoker or Pathologic Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 or Clinical Stage III HPV-Mediated (p16-Positive) Oropharyn...?
Do you have any of these conditions: Human Papillomavirus-16 Positive or Pathologic Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 or Pathologic Stage II HPV-Mediat...?
Do you have any of these conditions: Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 or Pathologic Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcin...?
Do you have any of these conditions: Pathologic Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 or Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcin...?
Do you have any of these conditions: smoker or Pathologic Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 or Clinical Stage III HPV-Mediated (p16-Positive) Oropharyng...?
Is your age greater than or equal to 18 yrs?
Do you have any of these conditions: Human Papillomavirus-16 Positive or Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 or smoker or Pathologic Stage III H...?
Do you have any of these conditions: Human Papillomavirus-16 Positive or Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 or Pathologic Stage III HPV-Mediate...?
Do you have any of these conditions: Pathologic Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 or Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carci...?
Do you have any of these conditions: Pathologic Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 or Human Papillomavirus-16 Positive or smoker or Pathologic Stage III ...?
Do you have any of these conditions: Pathologic Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 or Pathologic Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carc...?
Do you have any of these conditions: Pathologic Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 or smoker or Human Papillomavirus-16 Positive or Clinical Stage II HPV...?
Do you have any of these conditions: Pathologic Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 or smoker or Pathologic Stage II HPV-Mediated (p16-Positive) Orophary...?
Do you have any of these conditions: smoker or Pathologic Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 or Pathologic Stage III HPV-Mediated (p16-Positive) Orophary...?
Gender: Male or Female
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 with smoking status: >= 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)
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 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
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