What side effects are associated with this type of intervention?

The most common treatments for oropharyngeal cancer, particularly those involving immunotherapy with monoclonal antibodies such as nivolumab, can lead to a range of side effects. These include immune-related adverse events such as pneumonitis, rash, pruritus, and diarrhea. Severe adverse events can also occur, including grade 3 or 4 toxicities like pneumonia. Patients may require concomitant treatments such as steroids or other immunosuppressive agents to manage these side effects. Overall, while immunotherapy can be effective, it carries a risk of significant immune-related toxicities.

What prior FDA approvals exist?

Nivolumab, an immunotherapy with monoclonal antibodies, has been studied for its potential to improve overall survival and progression-free survival in patients with HPV-positive oropharyngeal cancer. This treatment works by helping the immune system attack cancer and interfering with tumor cell growth and spread. Other similar immunotherapy agents, such as pembrolizumab, have also been investigated for their efficacy in treating recurrent or metastatic squamous cell carcinoma of the head and neck, including oropharyngeal cancer. These treatments represent a significant advancement in the management of oropharyngeal cancer by leveraging the body's immune response to target and control tumor growth.

What other types of research exist?

Promising novel alternatives to Nivolumab for Oropharyngeal Cancer patients include Pembrolizumab, which is approved as a first-line therapy for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Additionally, the combination of Pembrolizumab with Cetuximab is being investigated and has shown encouraging response rates in treatment-refractory metastatic HNSCC. Other investigational approaches include metronomic chemotherapy combined with low-dose Nivolumab, which targets tumor angiogenesis and minimizes toxicity.

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Chemotherapy Agent

Immunotherapy for HPV-Positive Throat Cancer

Phase 3

Waitlist Available

Led By Nabil F Saba

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline up to 10 years

Awards & highlights

Pivotal Trial

No Placebo-Only Group

Summary

This trial is testing whether adding the drug nivolumab can help patients with a specific type of throat cancer live longer and prevent the cancer from coming back. Nivolumab boosts the immune system to better fight the cancer. The study focuses on patients whose cancer has spread to nearby areas.

Who is the study for?

Adults with intermediate-risk HPV-positive oropharyngeal cancer that has spread locally but not to distant sites. Participants must have adequate organ function, no prior treatments for this cancer, and cannot be pregnant or breastfeeding. They should not have a history of severe allergic reactions to chemotherapy agents like cisplatin or immune conditions that require steroids.

What is being tested?

The trial is testing if adding maintenance immunotherapy (nivolumab) after standard treatment with radiation and chemotherapy (cisplatin) improves survival in patients compared to just the standard treatment alone. It's looking at overall survival and progression-free survival as key outcomes.

What are the potential side effects?

Possible side effects include typical chemotherapy-related issues such as nausea, fatigue, hair loss, and increased risk of infection. Nivolumab may cause immune system-related side effects affecting various organs, infusion reactions, skin rash, hormone gland problems (like thyroid), and can worsen pre-existing autoimmune diseases.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I had hepatitis C but am cured, or I'm being treated with no detectable virus.

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I am not on high-dose steroids or other immune-weakening drugs that will continue during treatment.

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My cancer has not spread to distant parts of my body or into the fluid around my brain and spinal cord.

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I do not have an active or history of severe autoimmune disease that could worsen.

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I have not had any treatment for my p16 positive throat cancer.

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I haven't had any cancer treatment outside this study after my last radiation and chemotherapy.

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My throat cancer is linked to HPV and I have a history of heavy smoking.

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I am not allergic to nivolumab or similar medications.

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I am HIV positive but have an undetectable viral load on a stable treatment.

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I had early-stage cancer surgery without any follow-up treatments over 5 years ago.

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I am fully active or restricted in physically strenuous activity but can do light work.

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I am fully active or can carry out light work.

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I am 18 years old or older.

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I have not had radiation therapy for tumors in my head, neck, skull base, or brain.

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My hepatitis B virus is under control with treatment.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline up to 10 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline up to 10 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline up to 10 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Negative (standardized qualitative) 12 week post therapy (cisplatin + RT) FDG PET/CT associated with PFS for patients who have a PET/CT

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

Overall survival (OS)

Secondary study objectives

PET/CT scan

Post therapy (cisplatin + RT) FDG PET/CT with saliva or plasma levels of HPV deoxyribonucleic acid (DNA)

Prognostic effect of baseline PD-L1 expression (positive versus [vs.] negative) on OS and PFS

+5 more

Side effects data

From 2024 Phase 3 trial • 529 Patients • NCT02017717

80%

Fatigue

70%

Diarrhoea

70%

Headache

40%

Vomiting

40%

Aspartate aminotransferase increased

40%

Rash maculo-papular

40%

Alanine aminotransferase increased

40%

Lipase increased

30%

Partial seizures

30%

Hemiparesis

30%

Gait disturbance

30%

Fall

30%

Cough

30%

Dry skin

30%

Amylase increased

30%

Nausea

30%

Confusional state

20%

Malignant neoplasm progression

20%

Pyrexia

20%

Candida infection

20%

Mucosal infection

20%

Decreased appetite

20%

Back pain

20%

Dysphonia

20%

Hypotension

20%

Colitis

20%

Hyperthyroidism

20%

Oedema peripheral

20%

Muscular weakness

20%

Hypothyroidism

10%

Tinnitus

10%

Cushingoid

10%

Diabetic ketoacidosis

10%

Procedural haemorrhage

10%

Blood bilirubin increased

10%

Bradycardia

10%

Sinus tachycardia

10%

Hyperglycaemia

10%

Hypocalcaemia

10%

Neck pain

10%

Brain oedema

10%

Hydrocephalus

10%

Lethargy

10%

Seizure

10%

Hypertension

10%

Palpitations

10%

Cheilitis

10%

Presyncope

10%

Face oedema

10%

Oedema

10%

Conjunctivitis

10%

Enterocolitis infectious

10%

Oral candidiasis

10%

Pneumonia

10%

Sinusitis

10%

Staphylococcal infection

10%

Blood alkaline phosphatase increased

10%

Spinal pain

10%

Tremor

10%

Dizziness

10%

Dysarthria

10%

Urinary retention

10%

Dyspnoea exertional

10%

Nasal congestion

10%

Pneumonitis

10%

Dermatitis

10%

Erythema

10%

Rash

10%

Klebsiella infection

10%

Hypomagnesaemia

10%

Syncope

10%

Haemorrhage intracranial

10%

Pancreatitis

10%

Cholecystitis

10%

Upper respiratory tract infection

10%

Acute kidney injury

10%

Dermatitis bullous

10%

Lymphopenia

10%

Optic nerve disorder

10%

Visual impairment

10%

Dehydration

10%

Hypokalaemia

10%

Scoliosis

10%

Cognitive disorder

10%

Memory impairment

10%

Hallucination

10%

Insomnia

10%

Irritability

10%

Urinary incontinence

10%

Dyspnoea

10%

Dermatitis acneiform

10%

Pelvic venous thrombosis

10%

Sepsis

100%

80%

60%

40%

20%

Study treatment Arm

Cohort 1: Arm N1+I3

Cohort 2: Arm B

Part A Cohort 1c: Arm N3+RT+TMZ

Part A Cohort 1d: Arm N3+RT

Part B Cohort 1c: Arm N3+RT+TMZ

Part B Cohort 1d: Arm N3+RT

Cohort 1: Arm N3

Cohort 1b: Arm N3+I1

Cohort 2: Arm N3

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: Arm C (nivolumab)Experimental Treatment6 Interventions

Patients receive nivolumab IV over 30 minutes every 4 weeks for 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo CT or FDG PET/CT scans throughout the trial. Patients may undergo ECHO as clinically indicated. Additionally, patients undergo blood sample collection during screening.

Group II: Arm A (cisplatin, IMRT, nivolumab)Experimental Treatment8 Interventions

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. Patients undergo CT or FDG PET/CT scans throughout the trial. Patients may undergo ECHO as clinically indicated. Additionally, patients undergo blood sample collection during screening.

Group III: Arm B (cisplatin, IMRT, observation)Active Control8 Interventions

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. Patients undergo CT or FDG PET/CT scans throughout the trial. Patients may undergo ECHO as clinically indicated. Additionally, patients undergo blood sample collection during screening.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Computed Tomography

2017

Completed Phase 2

~2790

Biospecimen Collection

2004

Completed Phase 3

~2030

Cisplatin

2013

Completed Phase 3

~3120

Echocardiography

2013

Completed Phase 4

~11580

Positron Emission Tomography

2011

Completed Phase 2

~2200

Intensity-Modulated Radiation Therapy

2010

Completed Phase 3

~2140

Nivolumab

2015

Completed Phase 3

~4010

0 / 15Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for oropharyngeal cancer include immunotherapy, chemotherapy, and radiation therapy. Immunotherapy, such as nivolumab, uses monoclonal antibodies to help the immune system recognize and attack cancer cells, interfering with their growth and spread. Chemotherapy, like cisplatin, works by killing cancer cells or stopping them from dividing. Radiation therapy uses high-energy rays to destroy cancer cells and shrink tumors. These treatments are crucial for oropharyngeal cancer patients as they target the cancer through different mechanisms, potentially improving overall survival and disease-free survival.

Immunotherapy of head and neck squamous cell carcinoma (HNSCC). Immune checkpoint blockade.Profile of pembrolizumab in the treatment of head and neck squamous cell carcinoma: design development and place in therapy.Novel therapy for nasopharyngeal carcinoma--where are we.