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

Plain English Summary

Testing Immunotherapy Versus Observation in Patients With HPV Throat Cancer is a Phase 3 clinical trial sponsored by National Cancer Institute (NCI) studying Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8. This trial tests if continuing immunotherapy (nivolumab) after radiation and chemotherapy improves survival and stops cancer from coming back in patients with HPV-positive throat cancer. It's for patients with HPV-positive throat cancer that has spread to nearby tissue or lymph nodes, and who have completed radiation and chemotherapy. Participants will receive nivolumab or observation, and will be followed for up to 10 years to see if the treatment works. Patients can choose to participate in this trial or opt for standard treatment without immunotherapy. The trial aims to enroll 636 participants.

Official Summary

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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Age 18 or older, in good health (ECOG 0 or 1), with HPV-positive throat cancer that has spread to nearby tissue or lymph nodes. No history of allergic reactions to nivolumab or platinum-based chemotherapy, no prior treatment for HPV-positive throat cancer, and no other serious health issues. Not pregnant or breastfeeding, and using effective contraception if of childbearing potential. Measurable disease, with recent imaging scans showing the size of the cancer. This trial is studying Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures focus on overall survival and progression-free survival, which means patients will know if the treatment helps them live longer and without cancer coming back. The specific primary outcome measures are: Overall survival (OS) (From randomization to death, assessed up to 10 years); Negative (standardized qualitative) 12 week post therapy (cisplatin + radiation therapy [RT]) FDG positron emission tomography/computed tomography (PET/CT) associated with OS for patients who have a PET/CT (At 12 weeks post therapy); Negative (standardized qualitative) 12 week post therapy (cisplatin + RT) FDG PET/CT associated with PFS for patients who have a PET/CT (At 12 weeks post therapy). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial addresses a critical gap in treatment options for HPV-positive throat cancer, offering a potential new approach to improve survival and quality of life. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, where improved treatment options are needed.

Investor Insight

The large market size and competitive landscape in oncology, along with the high approval probability for innovative treatments, make this trial a significant investment opportunity. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 636 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor if you have HPV-positive throat cancer that has spread to nearby tissue or lymph nodes and if you are a good candidate for this trial. Undergo blood tests, imaging scans, and other procedures as part of the trial. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: CROSSOVER
• Masking: NONE
• Enrollment: 636 participants

Interventions

• PROCEDURE: Biospecimen Collection — Undergo blood sample collection
• DRUG: Cisplatin — Given IV
• PROCEDURE: Computed Tomography — Undergo CT or PET/CT
• PROCEDURE: Echocardiography Test — Undergo ECHO
• OTHER: Fludeoxyglucose F-18 — Receive FDG

Primary Outcomes

• Overall survival (OS) (From randomization to death, assessed up to 10 years)
• Negative (standardized qualitative) 12 week post therapy (cisplatin + radiation therapy [RT]) FDG positron emission tomography/computed tomography (PET/CT) associated with OS for patients who have a PET/CT (At 12 weeks post therapy)
• Negative (standardized qualitative) 12 week post therapy (cisplatin + RT) FDG PET/CT associated with PFS for patients who have a PET/CT (At 12 weeks post therapy)

Secondary Outcomes

• Progression-free survival (PFS) (From randomization to date of progression, second primary tumor from the head and neck region, or death, assessed up to 10 years)
• Prognostic effect of baseline PD-L1 expression (positive versus [vs.] negative) on OS and PFS (Baseline up to 10 years)
• Prognostic effect of baseline saliva and/or plasma human papillomavirus (HPV) status (positive vs. negative) on OS and PFS (Baseline up to 10 years)
• Prognostic value of maximum standardized uptake value (SUVmax) of primary tumor or neck nodal metastasis of baseline FDG PET/CT for OS (Baseline up to 10 years)
• Prognostic value of SUVmax of primary tumor or neck nodal metastasis of baseline FDG PET/CT for PFS (Baseline up to 10 years)

Full Eligibility 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 patient, regardless of 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; a

Trial Locations

• Thomas Hospital, Fairhope, Alabama, United States
• Mobile Infirmary Medical Center, Mobile, Alabama, United States
• Anchorage Associates in Radiation Medicine, Anchorage, Alaska, United States
• Anchorage Radiation Therapy Center, Anchorage, Alaska, United States
• Alaska Breast Care and Surgery LLC, Anchorage, Alaska, United States
• Alaska Oncology and Hematology LLC, Anchorage, Alaska, United States
• Alaska Women's Cancer Care, Anchorage, Alaska, United States
• Anchorage Oncology Centre, Anchorage, Alaska, United States
• Katmai Oncology Group, Anchorage, Alaska, United States
• Providence Alaska Medical Center, Anchorage, Alaska, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• HPV-mediated oropharyngeal carcinoma, head and neck cancer, immunotherapy, clinical trials, oncology

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