Recurrent Respiratory PapillomatosisPhase 2NCT02632344
Pembrolizumab for HPV-associated Recurrent Respiratory Papilloma Patients
A Phase 2 study testing Pembrolizumab in people with Recurrent Respiratory Papillomatosis, run by Massachusetts General Hospital at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Recurrent Respiratory Papillomatosis
- What is being tested?
- Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 2 sitesUnited States
- Study dates
- Apr 2016to Dec 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
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- 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
- 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
Who cannot join
- 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.
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- --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.
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
NorthShore University HealthSystem
Evanston, Illinois, 60208
About this study
Official title: Pembrolizumab for HPV-associated Recurrent Respiratory Papilloma Patients With Laryngeal, Tracheal and/or Pulmonary Involvement
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.
Read the 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.
- Conditions
- Recurrent Respiratory Papillomatosis
- Being tested
- Pembrolizumab
- Keywords
- Laryngeal papilloma, recurrent, Respiratory papillomatosis, Juvenile-onset recurrent respiratory papillomatosis, Human papillomavirus, Virally-related diseases
- Medical subject headings
- Recurrent respiratory papillomatosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called Keytruda, MK-3475
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 2 years
Number of Participants With Adverse Events Through CTCAE
To determine the safety and tolerability of pembrolizumab in subjects with RRP.
Measured: Up to 3 years after enrollment of the last the patient
Secondary outcomes (1)
Assess Duration of Response
To evaluate the response duration in subjects receiving pembrolizumab.
Measured: Time from observed partial response to the development of progressive disease.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2015 (estimated)
- Study startApr 2016
- Primary completionFeb 2022
- Study completionDec 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Recurrent Respiratory PapillomatosisStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Sara Pai, MD, PhD, Massachusetts General Hospital
- Investigators
- Sara Pai, MD PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02632344
- Sponsor's protocol ID
- 15-469
- Status last verified
- Apr 2026
- First submitted
- 10 Dec 2015
- Last updated
- 30 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pembrolizumab for HPV-associated Recurrent Respiratory Papilloma Patients With Laryngeal, Tracheal and/or Pulmonary Involvement
- ClinicalTrials.gov ID
- NCT02632344
- Acronym / sponsor ID
- 15-469
- Conditions
- Recurrent Respiratory Papillomatosis
- Keywords
- Laryngeal papilloma, recurrent, Respiratory papillomatosis, Juvenile-onset recurrent respiratory papillomatosis, Human papillomavirus, Virally-related diseases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Apr 2016 (actual)
- Primary completion
- Feb 2022 (actual)
- Study completion
- Dec 2025 (actual)
- First posted
- 16 Dec 2015 (estimated)
- Results
- Posted 3 Jul 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab | Experimental | Drug: PembrolizumabPembrolizumab 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 |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (25 listed)
- 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.
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabAlso: Keytruda, MK-3475200 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. | Drug | Pembrolizumab |
Primary outcome
Overall Response Rate Via Endoscopic Lesional Burden Score and/or RECIST
Time frame: Up to 2 years
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.
Number of Participants With Adverse Events Through CTCAE
Time frame: Up to 3 years after enrollment of the last the patient
To determine the safety and tolerability of pembrolizumab in subjects with RRP.
1 secondary outcome
Assess Duration of Response
Time frame: Time from observed partial response to the development of progressive disease.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Recurrent Respiratory Papillomatosis (RRP)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sara Pai, MD PhD principal investigator
Massachusetts General Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab in people with Recurrent Respiratory Papillomatosis, run by Massachusetts General Hospital 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 25 inclusion and 20 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 30 Apr 2026. 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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Overall Response Rate Via Endoscopic Lesional Burden Score and/or RECIST (time frame: Up to 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Apr 2026.