Pembrolizumab for HPV-associated Recurrent Respiratory Papilloma Patients

NCT02632344 | Completed Phase 2 Results DMC

• 1 other identifier: 15-469
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Recurrent Respiratory Papillomatosis

Keywords

Laryngeal papilloma, recurrent; Respiratory papillomatosis; Juvenile-onset recurrent respiratory papillomatosis; Human papillomavirus; Virally-related diseases

Outcome Measures

Primary Outcomes (2)

• Overall Response Rate Via Endoscopic Lesional Burden Score and/or RECIST

  A Simon two-stage design was used to assess best objective response rate based on endoscopic lesional burden and Response Evaluation Criteria in Solid Tumors (RECIST). For the endoscopic lesions burden score,T=the range of the score is 0 to 83. A lower score means decreased disease burden.

  Up to 2 years

• Number of Participants With Adverse Events Through CTCAE

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

  Up to 3 years after enrollment of the last the patient

Secondary Outcomes (1)

• Assess Duration of Response

  Time from observed partial response to the development of progressive disease.

Study Arms (1)

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

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

200 mg will be administered as a 30 minute IV infusion every 3 weeks on day 1 of each cycle after all procedures/assessments have been completed.

Also known as: Keytruda, MK-3475

Pembrolizumab

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent for the trial.
• Be 12 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 calculated 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

You may not qualify if:

• 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.
• 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 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

NorthShore University HealthSystem

Evanston, Illinois, 60208, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Recurrent respiratory papillomatosis

Interventions

pembrolizumab

Results Point of Contact

• Title: Dr. Sara Pai, Principal Investigator
• Organization: Massachusetts General Hospital

sarapaimdphd@gmail.com

617-726-5251

Study Officials

• Sara Pai, MD PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Sara Pai, MD, PhD

Study Record Dates

• First Submitted: December 10, 2015
• First Posted: December 16, 2015
• Study Start: April 1, 2016
• Primary Completion: February 1, 2022
• Study Completion: December 1, 2025
• Last Updated: April 30, 2026
• Results First Posted: July 3, 2023

Record last verified: 2026-04

Locations

US (2)