This study is currently recruiting participants.
Number
21-C-0013
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: Participants currently recruited/enrolled Gender: Male & Female Min Age: 18 Years Max Age: 120 Years
Referral Letter Required
No
Population Exclusion(s)
Pregnant Women;Fetuses;Children
Keywords
Human Papilloma Virus; Dose excalation; laryngotracheal disease; papillomatous disease; Avelumab
Recruitment Keyword(s)
None
Condition(s)
Recurrent Respiratory Papillomatosis; Papillomavirus Infections; Papillomaviridae
Investigational Drug(s)
PRGN-2012
Investigational Device(s)
Intervention(s)
Drug: PRGN-2012
Supporting Site
National Cancer Institute
Recurrent respiratory papillomatosis (RRP) is a rare disease. It is caused by the human papillomavirus (HPV). RRP affects the upper and lower respiratory tracts. It is difficult to treat and can be fatal. Researchers want to see if PRGN-2012 can help.
Objective:
To find a safe, tolerable dose of PRGN-2012 and to see if it works in treating RRP.
Eligibility:
Adults 18 and older who have RRP
Design:
Participants will be screened with a medical history and physical exam. They will have blood tests and viral studies. They may have a computed tomography (CT) scan of the neck and/or chest. The structures inside their nose, throat, larynx (voice box), and upper windpipe will be viewed using a small tube with a built-in camera (endoscope). Their arm veins will be evaluated. They will have a pregnancy test, if needed.
Screening tests will be repeated during the study.
Participants will have surgery. Their papilloma will be removed. They will have another surgery if it grows back. They will have to stay at the hospital for 1 to 2 days after each surgery.
Participants will complete questionnaires about how much RRP affects their voice.
Participants will get PRGN-2012 as an injection under the skin on days 1, 15, 43, and 85.
Participants will have visits 6, 12, and 24 weeks after their last dose of PRGN-2012. These visits will assess the safety of PRGN-2012 and disease response to the treatment. After the 24-week visit, participants will be called every 3 months for 2 years.
Participation will last for up to 3 years.
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INCLUSION CRITERIA: - Age 18 years and older - Male or female patients with clinical diagnosis of RRP --Histological diagnosis of papilloma confirmed by pathology report from a CLIA-certified (or comparable) laboratory --Presence of laryngotracheal papillomas accessible for endoscopic surgical cleanout (with or without pulmonary RRP) --A history of >= 3 surgical interventions in the last 12 months (prior to Day 1) for control of RRP - Clinical performance status of ECOG of 0-1 - Willing to undergo endoscopic evaluation and operative interventions with biopsies in compliance with this protocol - No systemic therapy for RRP for at least 3 half-lives of the prior drug(s). A 30-day washout is required for systemic bevacizumab treatment - Subjects who have received prior immunotherapy for RRP are permitted - Subjects must have adequate organ and marrow function as defined below: WBC >2,000/mcL Absolute Neutrophil Count >=1,500/mcL Hemoglobin >9.0 g/dL Platelets >=100,000/mcL total bilirubin <= 1.5 mg/dL, except in subjects with Gilbert s Syndrome who must have a total bilirubin < 3.0 mg/dL AST(SGOT)/ALT(SGPT) <=2.5 X institutional upper limit of normal PT/INR and PTT <= upper limit of normal Creatinine within normal institutional limits OR creatinine clearance >=50 mL/min/1.73 m^2 for subjects with creatinine levels above institutional normal - Sexually active subjects (men and women) of reproductive potential must agree to use two methods of contraception: one highly effective and one other effective method throughout vaccine treatment and for at least 120 days after vaccine treatment. Highly effective methods are defined as: Intrauterine device (IUD), hormonal (birth control pills, injections, implants), tubal ligation and partner s vasectomy; other effective methods are defined as: latex condom, diaphragm and cervical cap. - Seronegative for hepatitis B antigen, positive hepatitis B tests can be further evaluated by confirmatory tests (Hep B DNA quant, HBV viral load), and if confirmatory tests are negative, the subject can be enrolled. - Seronegative for hepatitis C antibody unless antigen negative. If hepatitis C antibody test is positive, then subjects must be tested for the presence of antigen by Hep C RNA quant, HCV viral load and be HCV RNA negative - All subjects must have the ability to understand and willingness to sign a written informed consent EXCLUSION CRITERIA: - A history of surgical debridement of papillomas such that in the opinion of the study team a subject is unlikely to be able to safely have a six-week interval between surgical interventions. - History of significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (>= New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication. - Any severe acute or chronic medical or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior, liver disease, lung disease (with the exception of what is specified in inclusion criteria), or laboratory abnormalities that, in the opinion of the investigators, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results and in the judgment of the investigator, would make the subject inappropriate for entry into this study. Subjects with mild to moderate asthma or chronic obstructive pulmonary disease (COPD) well controlled with oral or inhaled medications are permitted to enroll. - Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled, topical intranasal or intro-ocular steroids, and adrenal replacement doses <10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. - Subjects who are receiving any other investigational agents - Persisting toxicity related to prior therapy of Grade >1 NCI-CTCAE v 5.0; however, alopecia, sensory neuropathy Grade <= 2 or other Grade <= 2 AEs not constituting a safety risk based on investigator's judgment are acceptable. - Known alcohol or drug abuse. - Subject, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study. - History of allergy to study drug components. - Pregnant women are excluded from this study because PRGN-2012 is an agent with unknown potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with PRGN-2012, breastfeeding should be discontinued if the mother is treated with PRGN-2012. These potential risks may also apply to other agents used in this study.
- Age 18 years and older
- Male or female patients with clinical diagnosis of RRP
--Histological diagnosis of papilloma confirmed by pathology report from a CLIA-certified (or comparable) laboratory
--Presence of laryngotracheal papillomas accessible for endoscopic surgical cleanout (with or without pulmonary RRP)
--A history of >= 3 surgical interventions in the last 12 months (prior to Day 1) for control of RRP
- Clinical performance status of ECOG of 0-1
- Willing to undergo endoscopic evaluation and operative interventions with biopsies in compliance with this protocol
- No systemic therapy for RRP for at least 3 half-lives of the prior drug(s). A 30-day washout is required for systemic bevacizumab treatment
- Subjects who have received prior immunotherapy for RRP are permitted
- Subjects must have adequate organ and marrow function as defined below:
WBC >2,000/mcL
Absolute Neutrophil Count >=1,500/mcL
Hemoglobin >9.0 g/dL
Platelets >=100,000/mcL
total bilirubin <= 1.5 mg/dL, except in subjects with Gilbert s Syndrome who must have a total bilirubin < 3.0 mg/dL
AST(SGOT)/ALT(SGPT) <=2.5 X institutional upper limit of normal
PT/INR and PTT <= upper limit of normal
Creatinine within normal institutional limits
OR
creatinine clearance >=50 mL/min/1.73 m^2 for subjects with creatinine levels above institutional normal
- Sexually active subjects (men and women) of reproductive potential must agree to use two methods of contraception: one highly effective and one other effective method throughout vaccine treatment and for at least 120 days after vaccine treatment. Highly effective methods are defined as: Intrauterine device (IUD), hormonal (birth control pills, injections, implants), tubal ligation and partner s vasectomy; other effective methods are defined as: latex condom, diaphragm and cervical cap.
- Seronegative for hepatitis B antigen, positive hepatitis B tests can be further evaluated by confirmatory tests (Hep B DNA quant, HBV viral load), and if confirmatory tests are negative, the subject can be enrolled.
- Seronegative for hepatitis C antibody unless antigen negative. If hepatitis C antibody test is positive, then subjects must be tested for the presence of antigen by Hep C RNA quant, HCV viral load and be HCV RNA negative
- All subjects must have the ability to understand and willingness to sign a written informed consent
EXCLUSION CRITERIA:
- A history of surgical debridement of papillomas such that in the opinion of the study team a subject is unlikely to be able to safely have a six-week interval between surgical interventions.
- History of significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (>= New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
- Any severe acute or chronic medical or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior, liver disease, lung disease (with the exception of what is specified in inclusion criteria), or laboratory abnormalities that, in the opinion of the investigators, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results and in the judgment of the investigator, would make the subject inappropriate for entry into this study. Subjects with mild to moderate asthma or chronic obstructive pulmonary disease (COPD) well controlled with oral or inhaled medications are permitted to enroll.
- Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled, topical intranasal or intro-ocular steroids, and adrenal replacement doses <10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
- Subjects who are receiving any other investigational agents
- Persisting toxicity related to prior therapy of Grade >1 NCI-CTCAE v 5.0; however, alopecia, sensory neuropathy Grade <= 2 or other Grade <= 2 AEs not constituting a safety risk based on investigator's judgment are acceptable.
- Known alcohol or drug abuse.
- Subject, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
- History of allergy to study drug components.
- Pregnant women are excluded from this study because PRGN-2012 is an agent with unknown potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with PRGN-2012, breastfeeding should be discontinued if the mother is treated with PRGN-2012. These potential risks may also apply to other agents used in this study.
Principal Investigator
Referral Contact
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