Clinical Trials /

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

NCT03238365

Description:

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.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Window of Opportunity Trial of Nivolumab and Tadalafil in Patients With Squamous Cell Carcinoma of the Head and Neck
  • Official Title: Window of Opportunity Trial of Nivolumab and Tadalafil in Patients With Squamous Cell Carcinoma of the Head and Neck

Clinical Trial IDs

  • ORG STUDY ID: 17P.210
  • NCT ID: NCT03238365

Conditions

  • Lip, Oral Cavity and Pharynx
  • Larynx

Interventions

DrugSynonymsArms
NivolumabOpdivoArm I (nivolumab)
TadalafilCialisArm II (nivolumab, tadalafil)

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVES:

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

      SECONDARY OBJECTIVES:

      I. 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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (nivolumab)Active ComparatorPatients receive nivolumab IV over 60 minutes on days 3 and 17 and undergo surgery on day 31.
    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.
    • Tadalafil

    Eligibility Criteria

            Inclusion Criteria:
    
              -  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
    
              -  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 24 hours of the start of study drugs
    
              -  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 less 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
    
            Exclusion Criteria:
    
              -  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
    
              -  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 receiving systemic steroid therapy or any other
                 form of immunosuppressive therapy within 14 days of initiation of therapy
    
              -  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; 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
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    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
    Safety Issue:
    Description: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

    Secondary Outcome Measures

    Measure:Prevalence of intratumoral immune cell populations
    Time Frame:Baseline up to 29 months
    Safety Issue:
    Description: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.

    Details

    Phase:Early Phase 1
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Sidney Kimmel Cancer Center at Thomas Jefferson University

    Last Updated

    October 10, 2017