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Lip, Oral Cavity and PharynxEarly Phase 1NCT03238365

Window of Opportunity Trial of Nivolumab and Tadalafil in Patients With Squamous Cell Carcinoma of the Head and Neck

A Early Phase 1 study testing Nivolumab, Tadalafil and Therapeutic Conventional Surgery in people with Lip, Oral Cavity and Pharynx and Larynx, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This randomized pilot early phase I trial studies how well nivolumab with or without tadalafil work in treating patients with head and neck squamous cell carcinoma that has come back and can be removed by surgery. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lip, Oral Cavity and Pharynx, Larynx
What is being tested?
Nivolumab, Tadalafil and Therapeutic Conventional Surgery
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
2 sitesUnited States
Study dates
10 Aug 2017to 8 Sep 2022
Phase
Early Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Pathologically confirmed head and neck squamous cell carcinoma (HNSCC)
  • Any stage HNSCC of the 1) oral cavity, 2) oropharynx, 3) larynx, 4) hypopharynx, 5) nasal cavity/paranasal sinuses, 6) unknown primary considered to have resectable disease; patients with recurrent disease that is amenable to surgery are eligible
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • While blood cells 2000/ul or more
  • Absolute neutrophil count 1500/ul or more
  • Platelets 100,000/ul or more
Show all 14Show fewer
  • Hemoglobin 9 g/dl or more
  • Bilirubin less than or equal to 1.5 x the upper limit of normal (except subjects with Gilbert syndrome, who can have total bilirubin < 3 mg/dl)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3 x the upper limit of normal
  • Glomerular filtration rate (GFR) greater than or equal to 40 ml/min using the Cockcroft-Gault formula or serum creatinine less than or equal to 1.5 x upper limit of normal (ULN)
  • Women of reproductive potential should have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 21 days of study enrollment
  • Women of reproductive potential must use highly effective contraception methods to avoid pregnancy for 23 weeks after the last dose of study drugs; "women of reproductive potential" is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes; in addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level more than 40 mIU/mL
  • Men of reproductive potential who are sexually active with women of reproductive potential must use any contraceptive method with a failure rate of less than 1% per year; men who are receiving the study medications will be instructed to adhere to contraception for 31 weeks after the last dose of study drugs; men who are azoospermic do not require contraception
  • All subjects must be able to comprehend and sign a written informed consent document

Who cannot join

  • Patients with nasopharyngeal carcinoma, salivary gland or skin primaries
  • Patients with any anginal chest pain; defined by a known diagnosis of angina; or defined by chest pressure, squeezing, radiating pain to arms, shoulders, or neck from the chest; with or without exertion
  • Patients taking nitrates
  • Patients taking PDE5 inhibitors more then 1/week during the previous 28 days
  • Patients with a secondary condition (sickle cell anemia) that cause priapism
  • Any history of a severe hypersensitivity reaction to any monoclonal antibody
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  • Any history of allergy to the study drug components
  • Any concurrent malignancies; exceptions include- basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer or in situ cervical cancer that has undergone potentially curative therapy; patients with a history of other prior malignancy must have been treated with curative intent and must have remained disease-free for 2 years post-diagnosis
  • Any diagnosis of immunodeficiency or current immunosuppressive therapy including >10mg/day of prednisone within 14 days of enrollment is not permitted.
  • Patients that have an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids (> 10 mg daily prednisone equivalents) or immunosuppressive agents; subjects with vitiligo, type I diabetes mellitus, or resolved childhood asthma/atopy would be an exception to this rule. Inhaled or topical steroids, and adrena replacement steroid doses =<10mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study; subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study
  • Patients must not be receiving any other investigational agents
  • Patients with uncontrolled intercurrent illnesses including, but not limited to an active infection requiring systemic therapy or a known psychiatric or substance abuse disorder(s) that would interfere with cooperation with the requirements of the trial
  • Patients must not be pregnant or breastfeeding
  • Patients with a known human immunodeficiency virus infection (HIV 1/2 antibodies) or acquired immunodeficiency syndrome (HIV/AIDS), active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
  • Patients with any evidence of current interstitial lung disease (ILD) or pneumonitis
  • Patients with prior history of ILD or non-infectious pneumonitis that required steroids
  • Patients who have received a live vaccine within 30 days of the planned start of study therapy

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Vanderbilt University

    Nashville, Tennessee, 37232

  • Sidney Kimmel Cancer Center at Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

Other trials in United States

About this study

This randomized pilot early phase I trial studies how well nivolumab with or without tadalafil work in treating patients with head and neck squamous cell carcinoma that has come back and can be removed by surgery. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread. Tadalafil may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving nivolumab and tadalafil may work better in treating patients head and neck squamous cell carcinoma.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To investigate whether adding the PDE5 inhibitor, tadalafil, to nivolumab therapy affects intratumoral and systemic anti-tumor immunity.

SECONDARY OBJECTIVES:

  1. Characterize the combined effects of nivolumab and tadalafil on safety, exosome composition and function, the composition of intratumoral immune cell populations, wound healing, and tumor radiographic response.
Medical subject headings
Lymphoid Interstitial Pneumonia, Laryngeal Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT03238365
Study groupRoleWhat they receive
Arm I (nivolumab)Active comparatorPatients receive nivolumab IV over 60 minutes on days 3 and 17 and undergo surgery on day 31.
Receives: Biological: Nivolumab; Procedure: Therapeutic Conventional Surgery
Arm II (nivolumab, tadalafil)ExperimentalPatients receive nivolumab IV over 60 minutes on days 3 and 17 and tadalafil PO QD on days 3-31. Patients then undergo surgery on day 31.
Receives: Biological: Nivolumab; Drug: Tadalafil; Procedure: Therapeutic Conventional Surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in immune cell polarization (Th1/Th2; M1/M2) in peripheral blood and tumor specimens using multiplex cytokine analysis

    Analyze the immune cell polarization (Th1/Th2; M1/M2) in peripheral blood and tumor specimen supernatants will look at an entire panel of inflammatory markers, utilizing Luminex technology with the milliplex MAP human cytokine/chemokine magnetic kit I

    Measured: Baseline up to day 31 of treatment

Secondary outcomes (1)

  1. Prevalence of intratumoral immune cell populations

    We will use immunohistochemistry (IHC) to determine the prevalence of intratumoral immune cell populations in patients treated with nivolumab and tadalafil as compared to patients treated with nivolumab alone.

    Measured: Baseline up to 29 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Aug 2017
  2. Study start10 Aug 2017
  3. Primary completion30 Jul 2019
  4. Study completion8 Sep 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03238365
Sponsor's protocol ID
17P.210
Other IDs
JT 10237
Status last verified
Apr 2025
First submitted
31 Jul 2017
Last updated
29 Apr 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Luginbuhl AJ, Johnson JM, Harshyne LA, Linnenbach AJ, Shukla SK, Alnemri A, Kumar G, Cognetti DM, Curry JM, Kotlov N, Antysheva Z, Degryse S, Mannion K, Gibson MK, Netterville J, Brown B, Axelrod R, Zinner R, Tuluc M, Gargano S, Leiby BE, Shimada A, Mahoney MG, Martinez-Outschoorn U, Rodeck U, Kim YJ, South AP, Argiris A. Tadalafil Enhances Immune Signatures in Response to Neoadjuvant Nivolumab in Resectable Head and Neck Squamous Cell Carcinoma. Clin Cancer Res. 2022 Mar 1;28(5):915-927. doi: 10.1158/1078-0432.CCR-21-1816.

    PubMed 34911681

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Nivolumab, Tadalafil and Therapeutic Conventional Surgery in people with Lip, Oral Cavity and Pharynx and Larynx, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in immune cell polarization (Th1/Th2; M1/M2) in peripheral blood and tumor specimens using multiplex cytokine analysis (time frame: Baseline up to day 31 of treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03238365, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2025.

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