Clinical Trials /

Pembrolizumab for HPV-associated Recurrent Respiratory Papilloma Patients With Laryngeal, Tracheal and/or Pulmonary Involvement

NCT02632344

Description:

This research study is evaluating an immune modulatory agent as a possible treatment for patients with Recurrent Respiratory Papillomatosis (RRP) with significant disease involving the larynx, trachea, and/or lungs. The investigators will be using Pembrolizumab as the treating agent.

Related Conditions:
  • Lung Papilloma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Study of Anti-PD-1 Therapy for HPV-associated Recurrent Respiratory Papilloma Patients With Laryngeal, Tracheal and/or Pulmonary Involvement

Title

  • Brief Title: Study of Anti-PD-1 Therapy for HPV-associated Recurrent Respiratory Papilloma Patients With Laryngeal, Tracheal and/or Pulmonary Involvement
  • Official Title: Study of Anti-PD-1 Therapy for HPV-associated Recurrent Respiratory Papilloma Patients With Laryngeal, Tracheal and/or Pulmonary Involvement
  • Clinical Trial IDs

    NCT ID: NCT02632344

    ORG ID: 15-469

    Trial Conditions

    Recurrent Respiratory Papillomatosis

    Trial Interventions

    Drug Synonyms Arms
    Pembrolizumab Keytruda, MK-3475 Pembrolizumab

    Trial Purpose

    This research study is evaluating an immune modulatory agent as a possible treatment for
    patients with Recurrent Respiratory Papillomatosis (RRP) with significant disease involving
    the larynx, trachea, and/or lungs. The investigators will be using Pembrolizumab as the
    treating agent.

    Detailed Description

    This research study is a Phase II clinical trial. Phase II clinical trials test the safety
    and effectiveness of an investigational intervention to learn whether the intervention works
    in treating a specific disease. The FDA (the U.S. Food and Drug Administration) has not
    approved Pembrolizumab for your specific disease but it has been approved for other uses.

    Pembrolizumab is a humanized monoclonal antibody. Pembrolizumab is being studied in several
    other clinical trials to see if it has an effect in helping the immune system to recognize
    and eliminate abnormal cells in the body. The antibody blocks a receptor expressed on immune
    cells, called T cells, and by blocking this receptor it has the potential to activate the T
    cells to kill abnormal cells, such as virally infected cells.

    In this research study, the investigators are looking at whether Pembrolizumab can restore
    the natural ability of the immune system to recognize and eliminate Human papillomavirus
    (HPV)-infected cells from the body.

    Trial Arms

    Name Type Description Interventions
    Pembrolizumab Experimental Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Treatment will be administered on Day 1 of each cycle after all procedures/assessments have been completed Pembrolizumab

    Eligibility Criteria

    Inclusion Criteria:

    - Be willing and able to provide written informed consent for the trial.

    - Be 18 years of age on day of signing informed consent.

    - Have histologically confirmed diagnosis of RRP that involves the trachea, lungs,
    and/or larynx. The latter of which has required 3 or more surgeries within a year to
    remove the lesions from their larynx. Subjects must have evaluable disease either
    based on RECIST 1.1 and/or endoscopic parameters, as discussed above.

    - Be required to provide tissue from a newly obtained biopsy of a tumor lesion.
    Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to
    study registration. Subjects for whom newly-obtained samples cannot be provided (e.g.
    inaccessible or subject safety concern) may submit an archived specimen only upon
    agreement from PI.

    - Have confirmed human papillomavirus-associated lesions based on in-situ hybridization
    testing and/or polymerase chain reaction which may be performed on a newly obtained
    biopsy or archived sample.

    - Have a performance status of 0 or 1 on the ECOG Performance Scale.

    - Demonstrate adequate organ function as defined in Table 1, all screening labs should
    be performed within 10 days of study registration System Laboratory Value

    - Hematological

    - Absolute neutrophil count (ANC) 1,500 /mcL

    - Platelets 100,000 / mcL

    - Hemoglobin 9 g/dL or 5.6 mmol/L without transfusion or EPO dependency
    (within 7 days of assessment)

    - Renal

    - Serum creatinine OR Measured or calculateda creatinine clearance 1.5 X
    upper limit of normal (ULN) OR

    - (GFR can also be used in place of creatinine or CrCl) 60 mL/min for
    subject with creatinine levels > 1.5 X institutional ULN

    - Hepatic

    - Serum total bilirubin 1.5 X ULN OR Direct bilirubin ULN for subjects
    with total bilirubin levels > 1.5 ULN

    - AST (SGOT) and ALT (SGPT) 2.5 X ULN OR 5 X ULN for subjects with liver
    metastases

    - Albumin >2.5 mg/dL

    - Coagulation

    - International Normalized Ratio (INR) or Prothrombin Time (PT)1.5 X ULN
    unless subject is receiving anticoagulant therapy as long as PT or PTT is
    within therapeutic range of intended use of anticoagulants.

    - Activated Partial Thromboplastin Time (aPTT) 1.5 X ULN unless subject is
    receiving anticoagulant therapy as long as PT or PTT is within therapeutic
    range of intended use of anticoagulants.

    - Creatinine clearance should be calculated per institutional standard.

    - Female subject of childbearing potential should have a negative urine or serum
    pregnancy within 72 hours prior to receiving any dose of study medication. If the
    urine test is positive or cannot be confirmed as negative, a serum pregnancy test
    will be required.

    - Female subjects of childbearing potential should be willing to use 2 methods of birth
    control or be surgically sterile, or abstain from heterosexual activity for the
    course of the study through 120 days after the last dose of study medication
    (Reference Section 5.7.2). Subjects of childbearing potential are those who have not
    been surgically sterilized or have not been free from menses for > 1 year. The
    methods of surgical sterilization include having had a hysterectomy (removal of the
    uterus), bilateral oophorectomy (removal of both ovaries), tubal ligation (having
    your tubes tied), and transvaginal occlusion (blocking the tubes with a coil).

    - Male subjects should agree to use an adequate method of contraception starting with
    the first dose of study therapy through 120 days after the last dose of study therapy

    Exclusion Criteria:

    - Is currently participating and receiving study therapy or has participated in a study
    of an investigational agent and received study therapy or used an investigational
    device within 4 weeks of the first dose of treatment.

    - Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
    other form of immunosuppressive therapy within 7 days prior to study registration.

    - Has a known history of active TB (Bacillus Tuberculosis)

    - Hypersensitivity to pembrolizumab or any of its excipients.

    - Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
    registration or who has not recovered (i.e., Grade 1 or at baseline) from adverse
    events due to agents administered more than 4 weeks earlier.

    - Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
    within 2 weeks prior to study registration or who has not recovered (i.e., Grade 1
    or at baseline) from adverse events due to a previously administered agent.

    --Note: Subjects with Grade 2 neuropathy are an exception to this criterion and may
    qualify for the study.

    - Recovery from effects of any major surgery or significant traumatic injury at least
    28 days before the first dose of study treatment. Endoscopic debridement of RRP
    lesions is NOT considered a major surgery

    - No known diagnosis of invasive squamous cell carcinoma within the previous 2 years.

    - Has a known malignancy that is progressing or requires active treatment. Exceptions
    include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that
    has undergone potentially curative therapy or in situ cervical cancer.

    - Has active autoimmune disease that has required systemic treatment in the past 2
    years (i.e. with use of disease modifying agents, corticosteroids or
    immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or
    physiologic corticosteroid replacement therapy for adrenal or pituitary
    insufficiency, etc.) is not considered a form of systemic treatment.

    - Has known history of, or any evidence of active, non-infectious pneumonitis.

    - Has an active infection requiring systemic therapy.

    - Has a history or current evidence of any condition, therapy, or laboratory
    abnormality that might confound the results of the trial, interfere with the
    subject's participation for the full duration of the trial, or is not in the best
    interest of the subject to participate, in the opinion of the treating investigator.

    - Has known psychiatric or substance abuse disorders that would interfere with
    cooperation with the requirements of the trial.

    - Is pregnant or breastfeeding, or expecting to conceive or father children within the
    projected duration of the trial, starting with the pre-screening or screening visit
    through 120 days after the last dose of trial treatment.

    - Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

    - Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

    - Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
    [qualitative] is detected).

    - Has received a live vaccine within 30 days of planned start of study therapy. --Note:
    Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
    are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live
    attenuated vaccines, and are not allowed.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Overall Response Rate Via Clinical Assessment and/or RECIST

    Secondary Outcome Measures

    Assess Quality of Life Via Self-Report Questionnaires

    Number of Participants with Adverse Events Through CTCAE

    Assess Change in Immune Biomarkers

    Trial Keywords

    Laryngeal papilloma, recurrent

    Respiratory papillomatosis

    Juvenile-onset recurrent respiratory papillomatosis

    Human papillomavirus

    Virally-related diseases