Pembrolizumab in Treating Patients with HPV-Associated Recurrent Respiratory Papillomatosis with Larynx, Trachea or Lung Involvement

Status: Active

Description

This phase II trial studies the side effects of pembrolizumab and to see how well it works in treating patients with human papillomavirus (HPV)-associated respiratory papillomatosis involving the larynx, trachea or lungs and has come back. Monoclonal antibodies, such as pembrolizumab, may block tumor growth in different ways by targeting and eliminating human papillomavirus related recurrent respiratory papilloma cells in the larynx, trachea, or lungs.

Eligibility Criteria

Inclusion Criteria

  • The subject or their legal guardian be willing and able to provide written informed consent for the trial
  • Have histologically confirmed diagnosis of RRP that involves the trachea, lungs, and/or larynx; if a subject is enrolled with laryngeal disease only, the subject must have undergone at least 3 or more surgeries/procedures in any one 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 principal investigator (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 Eastern Cooperative Oncology Group (ECOG) performance scale
  • Absolute neutrophil count (ANC) >= 1,500 /mcL, performed within 28 days of study registration
  • Platelets >= 100,000 / mcL, performed within 28 days of study registration
  • Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment), performed within 28 days of study registration
  • Serum creatinine =< 1.5 X institutional upper limit of normal (ULN) OR measured or calculated creatinine clearance should be calculated per institutional standard (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN, performed within 28 days of study registration
  • Serum total bilirubin =<1.5 X institutional ULN OR direct bilirubin =< institutional ULN for subjects with total bilirubin levels > 1.5 institutional ULN, performed within 28 days of study registration
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional ULN OR =< 5 X institutional ULN for subjects with liver metastases, performed within 28 days of study registration
  • Albumin >= 2.5 mg/dL, performed within 28 days of study registration
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X institutional ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants, performed within 28 days of study registration
  • Activated partial thromboplastin time (aPTT) =< 1.5 X institutional ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants, performed within 28 days of study registration
  • Female subject of childbearing potential should have a negative urine or serum pregnancy test within 28 days of study registration; 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; 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 known 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)
  • Has a known 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
  • Patients with invasive squamous cell carcinoma derived from their RRP who are not considered appropriate for surgery, radiation therapy, or chemotherapy by their treating oncology team may be considered eligible for the study
  • 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 a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
  • Evidence of interstitial lung disease
  • 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-programmed death (PD)-1, anti-programmed death ligand (PD-L)1, 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., hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [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

Locations & Contacts

Illinois

Evanston
NorthShore University HealthSystem-Evanston Hospital
Status: Active
Contact: Aaron D. Friedman
Email: AFriedman2@northshore.org

Massachusetts

Boston
Massachusetts General Hospital Cancer Center
Status: Active
Contact: Sara Isabel Pai
Phone: 617-724-4000
Email: sara.pai@mgh.harvard.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the best overall clinical response rate (overall response rate [ORR]: complete response [CR]+partial response [PR]) in subjects with recurrent respiratory papillomatosis (RRP) with extensive laryngeal, tracheal and/or pulmonary involvement based on clinical examination and/or Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

II. To determine the safety and tolerability of pembrolizumab in subjects with RRP.

SECONDARY OBJECTIVES:

I. To evaluate changes in the expression of various immune biomarkers and investigate the relationship between candidate efficacy/resistance immune biomarkers and anti-tumor activity of pembrolizumab utilizing pre- and on-treatment tissue biopsies and blood sampling.

II. To evaluate the response duration in subjects receiving pembrolizumab.

TERTIARY OBJECTIVES:

I. To assess the quality of life (QOL) with immunotherapy treatment as compared to standard of care treatment in RRP patients.

OUTLINE:

Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, every 8 weeks and 6 months for 1 year, and then every 24 weeks for up to 36 months.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Dana-Farber Harvard Cancer Center

Principal Investigator
Sara Isabel Pai

Trial IDs

Primary ID 15-469
Secondary IDs NCI-2016-00698
Clinicaltrials.gov ID NCT02632344