What is the mechanism of action of this treatment?

The most common treatments for Head and Neck Cancers (HNC) include PD-1 inhibitors and PDE5 inhibitors. PD-1 inhibitors, such as Pembrolizumab, block the PD-1 receptor on T-cells, preventing cancer cells from evading the immune system and enhancing the body's ability to detect and destroy cancer cells. PDE5 inhibitors, like Tadalafil, can modulate the immune environment by increasing blood flow and potentially enhancing the delivery of immune cells to the tumor site. These mechanisms are important for HNC patients as they offer potential improvements in immune response and targeted cancer treatment.

What side effects are associated with this type of intervention?

Common treatments for head and neck cancers, such as Pembrolizumab (a PD-1 inhibitor) and Tadalafil (a PDE5 inhibitor), have distinct side effect profiles. Pembrolizumab can lead to immune-related adverse events including skin reactions, endocrine disorders, and pneumonitis. Tadalafil, on the other hand, may cause headaches, dyspepsia, back pain, and muscle aches. When considering these treatments, it is important to discuss potential side effects with a healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

Pembrolizumab, a PD-1 inhibitor, has been FDA-approved for the treatment of recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). It is often used in patients whose tumors express PD-L1 or in those who have progressed on or after platinum-based chemotherapy. Other similar immune checkpoint inhibitors, such as nivolumab (another PD-1 inhibitor), have also been approved for HNSCC. These treatments work by enhancing the immune system's ability to fight cancer. There is limited information on the use of tadalafil, a PDE5 inhibitor, in the treatment of head and neck cancers, and it is currently being studied in combination with pembrolizumab for potential synergistic effects.

What other types of research exist?

Promising novel alternatives to Pembrolizumab and Tadalafil for head and neck cancer patients include Nivolumab, another PD-1 inhibitor, and Budigalimab, a novel anti-PD-1 monoclonal antibody. Both have demonstrated efficacy in clinical trials. Additionally, combination therapies involving immune checkpoint inhibitors and other agents are being actively explored and may offer new treatment avenues.

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Checkpoint Inhibitor

Tadalafil + Pembrolizumab for Head and Neck Cancer

Phase 2

Waitlist Available

Led By Joseph Califano

Research Sponsored by University of California, San Diego

Eligibility Criteria Checklist

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

Must have

Patients must have normal organ and marrow function

Patients (at least 18 years of age) must have recurrent or metastatic squamous cell carcinoma of the head and neck

Must not have

Concurrent systemic immunosuppressant therapy (e.g., cyclosporine A, tacrolimus, etc., or chronic administration of >10 mg/day of prednisone or equivalent)

Prior daily use of tadalafil or other long-acting PDE5 inhibitors for one month or greater within 3 months of trial enrollment

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

All Individual Drugs Already Approved

No Placebo-Only Group

Approved for 5 Other Conditions

Summary

This trial will test a combination of two drugs, pembrolizumab and tadalafil, to treat advanced head and neck cancer. The goal is to see if this combination is safe and more effective than using pembrolizumab alone. Pembrolizumab helps the immune system attack cancer by blocking a specific protein, while tadalafil helps by blocking another pathway. This approach aims to strengthen the immune system's ability to fight cancer. Pembrolizumab has been approved by the FDA for various cancers and has shown significant activity in treating advanced head and neck cancer.

Who is the study for?

Adults with recurrent or metastatic head and neck squamous cell carcinoma who have not used PD-1 or PD-L1 inhibitors in this setting, nor had certain heart conditions, autoimmune diseases, severe drug allergies, organ transplants, or are pregnant. They must have a life expectancy over 12 weeks and normal organ/marrow function.

What is being tested?

The trial is testing the safety and effectiveness of combining two drugs: pembrolizumab (an immunotherapy) and tadalafil (a medication originally for erectile dysfunction), to treat advanced head and neck cancer.

What are the potential side effects?

Possible side effects include immune-related reactions like inflammation in various organs, fatigue, skin rash; as well as headaches, indigestion from tadalafil. Serious cardiac events could occur due to pre-existing conditions.

Eligibility Criteria

Inclusion Criteria

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

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My organs and bone marrow are functioning normally.

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I am 18 or older with recurrent or metastatic squamous cell carcinoma of the head and neck.

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My cancer can be measured by tests.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am not on strong immune system suppressing drugs.

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I have used tadalafil or similar medications daily for at least a month in the past 3 months.

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I have had a condition where my eye's optic nerve was damaged due to poor blood supply.

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I am currently taking a strong medication that affects liver enzymes.

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I have a heart condition that blocks blood flow from my heart.

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I am currently taking medication that stimulates guanylate cyclase.

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I have had an organ transplant.

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I have not had a stroke in the last 6 months.

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I am currently using long-acting PDE5 inhibitors.

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I take medication for chest pain.

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I have a family history of retinal disorders like retinitis pigmentosa.

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I have not had a heart attack or uncontrolled heart issues in the last 3 months.

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I am currently taking nitrates for my condition.

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I have been treated with PD-1 or PD-L1 inhibitors for recurrent or metastatic cancer.

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I had a positive heart stress test without any effective heart treatment afterwards.

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I have a history of HIV or active hepatitis B or C.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 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

Overall Survival (OS)

Rate of Dose Limiting Toxicity (DLT)

Secondary study objectives

Adverse event rates

Progression free survival

Response measured by RECIST 1.1

Side effects data

From 2017 Phase 4 trial • 635 Patients • NCT02224846

Viral upper respiratory tract infection

Periodontitis

Prostatitis

Alanine aminotransferase increased

Upper respiratory tract infection

Abdominal pain upper

Chronic gastritis

Blood uric acid increased

Insomnia

Sleep disorder

Eczema

Rhinitis

Rhinitis allergic

Influenza

Pharyngitis

Enteritis

Diabetes mellitus

Gout

Back pain

Gastritis

Urinary tract infection

Dizziness

Epistaxis

Renal cyst

Gastric polyps

Gastrooesophageal reflux disease

Nephrolithiasis

Hypertension

Pyrexia

Large intestine polyp

Abdominal distension

Abdominal pain

Dental caries

Diarrhoea

Gamma-glutamyltransferase increased

Headache

Cough

100%

80%

60%

40%

20%

Study treatment Arm

2.5 mg/5 mg Tadalafil

5 mg Tadalafil

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

No Placebo-Only Group

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

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Tadalafil and PembrolizumabExperimental Treatment2 Interventions

Tadalafil for up to 12 months and pembrolizumab for up to 24 months.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pembrolizumab

FDA approved

Tadalafil

FDA approved

0 / 19Eligibility 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 Head and Neck Cancers (HNC) include PD-1 inhibitors and PDE5 inhibitors. PD-1 inhibitors, such as Pembrolizumab, block the PD-1 receptor on T-cells, preventing cancer cells from evading the immune system and enhancing the body's ability to detect and destroy cancer cells. PDE5 inhibitors, like Tadalafil, can modulate the immune environment by increasing blood flow and potentially enhancing the delivery of immune cells to the tumor site. These mechanisms are important for HNC patients as they offer potential improvements in immune response and targeted cancer treatment.

Novel Systemic Treatment Modalities Including Immunotherapy and Molecular Targeted Therapy for Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma.Immunotherapy for head and neck squamous cell carcinoma.The genetic landscape of programmed death ligand-1 (PD-L1) alterations in head and neck cancer.