Testing Maintenance Immunotherapy Versus Observation in Patients With Oropharynx Cancer (EA3161)

A Phase II/III Randomized Study of Maintenance Nivolumab Versus Observation in Patients With Locally Advanced, Intermediate Risk HPV Positive OPCA

Overview

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.

Key Inclusion Criteria

For a patient to be eligible for participation in this study, all of the following criteria must apply.

  • 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.

Learn More

To learn more, visit ClinicalTrials.Gov

Study Type

Phase II/III

Sponsor(s)

National Cancer Institute (NCI)