Pleuropulmonary BlastomaNCT03382158
International PPB/DICER1 Registry
An observational study of Pleuropulmonary Blastoma and Sertoli-Leydig Cell Tumor, run by Children's Hospitals and Clinics of Minnesota at 1 site in United States.
Trial summary
PPB has strong genetic implications, with a unique set of conditions in an individual or their family, occurring mostly in childhood and adolescence. The International PPB/DICER1 Registry first reported DICER1 germline loss-of-function variations in individuals with PPB and their family members. Read more about this study
- Who is it for?
- Ages 0 minutes to 100 yearsHealthy volunteers can take part
- Conditions the study is for
- Pleuropulmonary Blastoma, Sertoli-Leydig Cell Tumor, DICER1 Syndrome
- How many people
- 3,400 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Dec 2016to 6 Dec 2036
- How long will I take part?
- 10 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 0 minutes to 100 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: 1. For those with PPB: PPB primarily affects children so their participation is required. 2. For those with DICER1-associated conditions: There's a wide array of conditions associated with DICER1, that occur at a variety of ages, from the development of cysts in utero, to lung cysts and thyroid disease noted in grandparents. 3. The Investigators are aware that many individuals with PPB, and with conditions associated with DICER1, come from countries outside of the U.S. To exclude individuals outside the US, minority groups and non-English speaking groups would be a disservice to eligible patients and healthcare providers and would limit the sample size of this rare cancer study.
Who may be able to join
- Known or suspected PPB or related thoracic tumor
- Known or suspected sex-cord stromal tumor including Sertoli-Leydig cell tumor and gynandroblastoma (males or females)
- Other known or suspected DICER1-related condition including ovarian sarcoma, cystic nephroma, renal sarcoma, pineoblastoma, pituitary blastoma, nasal chondromesenchymal hamartoma, ciliary body medulloepithelioma and others
- Individuals with known or suspected DICER1 pathogenic variation regardless of whether they have an established DICER1-associated condition
- Informed consent by patient/ or parent/guardian (also, where appropriate: assent and HIPAA consent)
Who cannot join
- Absence of appropriate consent for Registry participation
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Children's Minnesota
Minneapolis, Minnesota, 55404
Paige HR Mallinger, MS, 612-813-7115, paige.mallinger@childrensmn.org
Melissa A Abraham, BS, 6128137231, melissa.abraham@childrensmn.org
About this study
Official title: International Pleuropulmonary Blastoma/DICER1 Registry (for PPB, DICER1 and Associated Conditions)
PPB has strong genetic implications, with a unique set of conditions in an individual or their family, occurring mostly in childhood and adolescence. The International PPB/DICER1 Registry first reported DICER1 germline loss-of-function variations in individuals with PPB and their family members. Conditions associated with DICER1 include Sertoli-Leydig cell tumor (SLCT), gynandroblastoma, ovarian sarcoma, peritoneal PPB, lung cysts, renal cysts, cystic nephroma (CN), anaplastic sarcoma of the kidney (ASK), Wilms tumor, primary DICER1-associated central nervous system (CNS) sarcoma, pineoblastoma, pituitary blastoma, multinodular goiter, thyroid carcinoma, nasal chondromesenchymal hamartoma, ciliary body medulloepithelioma (CBME), juvenile hamartomatous intestinal polyps, embryonal rhabdomyosarcoma (ERMS) and undifferentiated sarcoma. DICER1 variations may also be associated with macrocephaly and overgrowth syndrome.
The International PPB/DICER1 Registry estimates that 30-50 cases of Type I and Ir PPB and 40-60 cases of Types II and III PPB are diagnosed annually worldwide. In 2009, the International Pleuropulmonary Blastoma Registry began a prospective study to collect treatment data on individuals for whom therapy decisions were made by their treating institution.
Read the detailed description
PPB is a rare cancer of the lung presenting in early childhood, mostly commonly from birth to age ~72 months. PPB occurs within the lung or between the lung and the chest wall. There are three primary forms of PPB called Types I, II, and III PPB. PPB is related to an underlying change/mutation in a gene called DICER1 which impacts gene expression and cell growth. DICER1 mutations may also lead to the development of other tumors in children and adults.
The International PPB/DICER1 Registry offers information based on previous data from Registry participants and the medical literature and collaborative efforts with international rare tumor groups.
Retrospective and real-time central pathology review is encouraged. Therapy decisions remain at the discretion of the treating institution.
Children with Type I PPB require surgery and sometimes chemotherapy. Therapy decisions are the responsibility of the treating institution. Surgical guidelines are presented. It is unknown whether adjuvant chemotherapy improves cure rates for Type I PPB patients. Chemotherapy options include a 22-week regimen: 4 courses of vincristine, actinomycin D and cyclophosphamide (VAC) followed by 3 courses of vincristine and actinomycin D (VA).
Children with Types II and III PPB, require surgery, chemotherapy and sometimes radiation therapy. Many children with Types II or III PPB receive a single-arm multi-agent chemotherapy neo-adjuvant/adjuvant regimen of IVADo (ifosfamide, vincristine, actinomycin, doxorubicin) for 36 weeks. Second and possible 3rd look surgery may be considered for local control. Radiation therapy may be considered.
- Conditions
- Pleuropulmonary Blastoma, Sertoli-Leydig Cell Tumor, DICER1 Syndrome, Cystic Nephroma, Wilms Tumor, Pineoblastoma
- Keywords
- pleuropulmonary blastoma, PPB, DICER1, SLCT, Sertoli-Leydig Cell Tumor, Cystic Nephroma, CN, DICER1 mutation, DICER1 syndrome, Wilms Tumor, Pineoblastoma, Renal Sarcoma, ASK, Nodular Hyperplasia of Thyroid, Thyroid Nodules, Thyroid Carcinoma, Nasal Chondromesenchymal Hamartoma, NCMH, Ciliary Body Medulloepithelioma, CBME
- Medical subject headings
- Pleuropulmonary blastoma, Sertoli-Leydig Cell Tumor, Wilms Tumor, Pinealoma, Goiter, Nodular, Neuroblastoma, Pituitary Neoplasms, Rhabdomyosarcoma, Embryonal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Type I PPB | Type I PPB is an early manifestation of this malignant disease, cured in some cases by surgery. Surgical guidelines are presented. It is unknown whether adjuvant chemotherapy improves cure rates for individuals with Type I PPB. If the treating physicians select adjuvant chemotherapy treatment, chemotherapy options include a 22-week regimen: 4 courses of vincristine, actinomycin D and cyclophosphamide (VAC) followed by 3 courses of vincristine and actinomycin D (VA). Therapy decisions are the responsibility of the treating institution. | |
| Types II and III PPB | Types II and III PPB are aggressive sarcomas. Surgery and chemotherapy are necessary in all cases. Surgical guidelines are presented. Many children with Types II or III PPB receive a single-arm multi-agent chemotherapy neo-adjuvant/adjuvant regimen of IVADo (ifosfamide, vincristine, actinomycin, doxorubicin) for 36 weeks. Second and possible 3rd look surgery may be considered for local control. Radiation therapy may be considered. Specific therapy decisions are the responsibility of the treating institution. | |
| Type Ir PPB | Type Ir (regressed) PPB is a unique, purely cystic tumor which lacks a primitive cell component. The International PPB/DICER1 Registry will enroll and follow participants with Type Ir PPB, regardless of age. | |
| DICER1 Gene or Cond Assoc with DICER1 | The International PPB/DICER1 Registry for PPB, DICER1, and Associated Conditions study will enroll and follow participants who have DICER1 gene variants or conditions associated with DICER1. This could include Sertoli-Leydig cell tumor, cystic nephroma, thyroid nodules or carcinoma, intracranial sarcoma, and others. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-free survival
The primary endpoint for statistical analysis will be time from start treatment to an event, defined as the occurrence of progression or recurrence of PPB, occurrence of a second malignant neoplasm, or death from any cause that is at least possibly related to the original disease or treatment.
Measured: 7 years
Secondary outcomes (6)
Overall response to chemotherapy
The investigators will assess overall response to chemotherapy among participants with radiographically measurable tumor following initial surgery or biopsy.
Measured: 7 years
Overall survival
The investigators will assess overall survival and time to death from any cause among participants.
Measured: 7 years
Quality of life outcomes in individuals diagnosed with PPB.
Chemotherapy and surgery may have adverse effects on the quality of life outcomes. Multiple factors may impact quality of life for participants.This study will allow the investigators to assess the quality of life outcomes in participants with DICER1-related tumors and will compare outcomes to those with more common childhood cancers.
Measured: 7 years
Cardiac outcomes in individuals diagnosed with PPB.
Chemotherapy and surgery may have adverse effects on cardiac outcomes. This study will allow the investigators to assess the cardiac outcomes as measured by ejection fraction and shortening fraction via echocardiogram of participants with DICER1-related tumors, and compare outcomes to those with more common childhood cancers.
Measured: 7 years
Pulmonary function testing results in individuals diagnosed with PPB
Chemotherapy and surgery may have adverse effects on pulmonary outcomes. This study will allow the investigators to assess the pulmonary outcome of participants as ascertained by pulmonary function testing (forced vital capacity (FVC), FEV1(forced expiratory volume in 1 second)/FVC) with DICER1-related tumors, and compare outcomes to those with more common childhood cancers.
Measured: 7 years
Incidence of neoplasms in individuals with DICER1-related conditions or germline DICER1 variants. mutation.
This protocol will include individuals with germline DICER1 mutations and will calculate incidence rates of specific neoplasms in this population
Measured: 7 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2017
- Study start6 Dec 2016
- Primary completion6 Dec 2031 (estimated)
- Study completion6 Dec 2036 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (33)Papers the sponsor has linked to this study.
- Other trials for Pleuropulmonary BlastomaStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 3,400 participants (estimated)
- Target duration
- 10 Years
Sponsor and investigators
- Lead sponsor
- Children's Hospitals and Clinics of Minnesota
- Sponsor type
- University, hospital or other
- Collaborators
- Washington University School of Medicine, University of Cambridge, Emory University, Dana-Farber Cancer Institute, Phoenix Children's Hospital, Allina Health System, University of California, San Francisco, M.D. Anderson Cancer Center, UC Davis Children's Hospital, KK Women's and Children's Hospital, Children's Healthcare of Atlanta, Dayton Children's Hospital, Akron Children's Hospital, Starship Children's Hospital of New Zealand, Bronson Methodist Hospital, Rutgers Cancer Institute of New Jersey, Children's Hospital of Philadelphia, Children's Hospital Medical Center, Cincinnati, Connecticut Children's Medical Center, Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogache, Driscoll Children's Hospital, Hannover Medical School, Jewish General Hospital, Kaiser Permanente, King Faisal Specialist Hospital & Research Center, Kingston Health Sciences Centre, Massachusetts General Hospital, McGill University Health Centre/Research Institute of the McGill University Health Centre, National Institutes of Health (NIH), Royal Perth Hospital, Princess Margaret Hospital for Children, Roswell Park Cancer Institute, The Hospital for Sick Children, St. Jude Children's Research Hospital, Huntsman Cancer Institute, University of Virginia, University of Texas Southwestern Medical Center, Ann & Robert H Lurie Children's Hospital of Chicago, Prisma Health-Upstate, Prisma Health-Midlands, Shaukat Khanum Memorial Cancer Hospital & Research Centre, Memorial Sloan Kettering Cancer Center, University of Colorado, Denver, Seattle Children's Hospital, CHU de Quebec-Universite Laval, Yale University, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Kaplan Medical Center, Schneider Children's Medical Center, Israel, Mayo Clinic, Children's Hospital Los Angeles, BC Cancer Foundation, Koc Healthcare Istanbul American Hospital, Marmara University Hospital
- Responsible party
- Sponsor
- Investigators
- Kris Ann P Schultz, MD, Principal investigator, Children's Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03382158
- Sponsor's protocol ID
- FDAAA
- Status last verified
- Oct 2026
- First submitted
- 11 Oct 2017
- Last updated
- 26 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Vasta LM, McMaster ML, Harney LA, Ling A, Kim J, Harris AK, Carr AG, Damrauer SM, Rader DJ, Kember RL, Kanetsky PA, Nathanson KL, Pyle LC, Greene MH, Schultz KA, Stewart DR; Regeneron Genetics Center (RGC) Research Team. Lack of pathogenic germline DICER1 variants in males with testicular germ-cell tumors. Cancer Genet. 2020 Oct;248-249:49-56. doi: 10.1016/j.cancergen.2020.10.002. Epub 2020 Oct 24.
PubMed 33158809Bisogno G, Sarnacki S, Stachowicz-Stencel T, Minard Colin V, Ferrari A, Godzinski J, Gauthier Villars M, Bien E, Hameury F, Helfre S, Schneider DT, Reguerre Y, Lopez Almaraz R, Janic D, Cesen M, Kolenova A, Rascon J, Martinova K, Cosnarovici R, Pourtsidis A, Ben Ami T, Roganovic J, Koscielniak E, Schultz KAP, Brecht IB, Orbach D. Pleuropulmonary blastoma in children and adolescents: The EXPeRT/PARTNER diagnostic and therapeutic recommendations. Pediatr Blood Cancer. 2021 Jun;68 Suppl 4(Suppl 4):e29045. doi: 10.1002/pbc.29045. Epub 2021 Apr 7.
PubMed 33826235Schneider DT, Orbach D, Ben-Ami T, Bien E, Bisogno G, Brecht IB, Cecchetto G, Ferrari A, Godzinski J, Janic D, Lopez Almaraz R, Pourtsidis A, Roganovic J, Schultz KAP, Stachowicz-Stencel T, Fresneau B. Consensus recommendations from the EXPeRT/PARTNER groups for the diagnosis and therapy of sex cord stromal tumors in children and adolescents. Pediatr Blood Cancer. 2021 Jun;68 Suppl 4:e29017. doi: 10.1002/pbc.29017. Epub 2021 Mar 24.
PubMed 33760357Ferguson MJ, Ivanovich J, Stansell P, Vik TA, Helvie AE, Schmitt MR, Schultz KA, Dehner LP, Renbarger JL, Marshall MS. Previously unreported somatic variants in two patients with pleuropulmonary blastoma with metastatic brain recurrence. Pediatr Blood Cancer. 2021 May;68(5):e28825. doi: 10.1002/pbc.28825. Epub 2020 Nov 30. No abstract available.
PubMed 33258270Schneider KW, Cost NG, Schultz KAP, Svihovec S, Suttman A. Germline predisposition to genitourinary rhabdomyosarcoma. Transl Androl Urol. 2020 Oct;9(5):2430-2440. doi: 10.21037/tau-20-76.
PubMed 33209717Schultz KAP, Rednam SP, Kamihara J, Doros L, Achatz MI, Wasserman JD, Diller LR, Brugieres L, Druker H, Schneider KA, McGee RB, Foulkes WD. PTEN, DICER1, FH, and Their Associated Tumor Susceptibility Syndromes: Clinical Features, Genetics, and Surveillance Recommendations in Childhood. Clin Cancer Res. 2017 Jun 15;23(12):e76-e82. doi: 10.1158/1078-0432.CCR-17-0629.
PubMed 28620008Schultz KAP, Nelson AT, Kamihara J, Bauer AJ, Hatton J, Merideth MA, Stratton P, Harris AK, Field A, Dehner LP, Stewart DR, Hill DA, Messinger YH. DICER1-Related Tumor Predisposition. 2014 Apr 24 [updated 2026 Mar 25]. In: Adam MP, Bick S, Mirzaa GM, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK196157/
PubMed 24761742Gonzalez IA, Stewart DR, Schultz KAP, Field AP, Hill DA, Dehner LP. DICER1 tumor predisposition syndrome: an evolving story initiated with the pleuropulmonary blastoma. Mod Pathol. 2022 Jan;35(1):4-22. doi: 10.1038/s41379-021-00905-8. Epub 2021 Oct 1.
PubMed 34599283Terry W, Carlisle EM, Mallinger P, Nelson AT, Gordon D, Messinger YH, Field A, Dehner LP, Hill DA, Schultz KAP. Thoracic Sertoli-Leydig cell tumor: An alternative type of pleuropulmonary blastoma associated with DICER1 variation. Pediatr Blood Cancer. 2021 Nov;68(11):e29284. doi: 10.1002/pbc.29284. Epub 2021 Aug 16.
PubMed 34398502Hill DA, Ivanovich J, Priest JR, Gurnett CA, Dehner LP, Desruisseau D, Jarzembowski JA, Wikenheiser-Brokamp KA, Suarez BK, Whelan AJ, Williams G, Bracamontes D, Messinger Y, Goodfellow PJ. DICER1 mutations in familial pleuropulmonary blastoma. Science. 2009 Aug 21;325(5943):965. doi: 10.1126/science.1174334. Epub 2009 Jun 25.
PubMed 19556464Messinger YH, Stewart DR, Priest JR, Williams GM, Harris AK, Schultz KA, Yang J, Doros L, Rosenberg PS, Hill DA, Dehner LP. Pleuropulmonary blastoma: a report on 350 central pathology-confirmed pleuropulmonary blastoma cases by the International Pleuropulmonary Blastoma Registry. Cancer. 2015 Jan 15;121(2):276-85. doi: 10.1002/cncr.29032. Epub 2014 Sep 10.
PubMed 25209242Kebudi R, Dural O, Bay SB, Gorgun O, Onder S, Bilgic B, Yilmaz I, Iribas A, Arndt CA, Harris AK, Field A, Schultz KAP, Hill DA. Childhood Rhabdomyosarcoma of the Female Genital Tract: Association with Pathogenic DICER1 Variation, Clinicopathological Features, and Outcomes. J Pediatr Adolesc Gynecol. 2021 Aug;34(4):449-453. doi: 10.1016/j.jpag.2021.01.011. Epub 2021 Jan 20.
PubMed 33484847Golmard L, Vasta LM, Duflos V, Corsini C, Dubois d'Enghien C, McMaster ML, Harney LA, Carr AG, Ling A, Dijoud F, Gauthier A, Miettinen M, Cost NG, Gauthier-Villars M, Orbach D, Irtan S, Haouy S, Schultz KA, Stoppa-Lyonnet D, Coupier I, Stewart DR, Sirvent N. Testicular Sertoli cell tumour and potentially testicular Leydig cell tumour are features of DICER1 syndrome. J Med Genet. 2022 Apr;59(4):346-350. doi: 10.1136/jmedgenet-2020-107434. Epub 2021 Mar 29.
PubMed 33782093Caron CP, Turcotte B, Pelland-Marcotte MC, Schultz KAP, Harvey I, Bolduc S. Case - Bilateral and recurrent pediatric cystic nephroma associated with DICER1 mutation. Can Urol Assoc J. 2021 May;15(5):E290-E292. doi: 10.5489/cuaj.6836. No abstract available.
PubMed 33119505Vasta LM, Khan NE, Higgs CP, Harney LA, Carr AG, Harris AK, Schultz KAP, McMaster ML, Stewart DR. Hematologic indices in individuals with pathogenic germline DICER1 variants. Blood Adv. 2021 Jan 12;5(1):216-223. doi: 10.1182/bloodadvances.2020002651.
PubMed 33570641
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- International Pleuropulmonary Blastoma/DICER1 Registry (for PPB, DICER1 and Associated Conditions)
- ClinicalTrials.gov ID
- NCT03382158
- Acronym / sponsor ID
- FDAAA
- Conditions
- Pleuropulmonary Blastoma, Sertoli-Leydig Cell Tumor, DICER1 Syndrome, Cystic Nephroma, Wilms Tumor, Pineoblastoma
- Keywords
- pleuropulmonary blastoma, PPB, DICER1, SLCT, Sertoli-Leydig Cell Tumor, Cystic Nephroma, CN, DICER1 mutation
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 3,400 participants (estimated)
- Lead sponsor
- Children's Hospitals and Clinics of MinnesotaUniversity, hospital or other
- Collaborators
- Washington University School of Medicine, University of Cambridge, Emory University, Dana-Farber Cancer Institute, Phoenix Children's Hospital, Allina Health System, University of California, San Francisco, M.D. Anderson Cancer Center, UC Davis Children's Hospital, KK Women's and Children's Hospital, Children's Healthcare of Atlanta, Dayton Children's Hospital, Akron Children's Hospital, Starship Children's Hospital of New Zealand, Bronson Methodist Hospital, Rutgers Cancer Institute of New Jersey, Children's Hospital of Philadelphia, Children's Hospital Medical Center, Cincinnati, Connecticut Children's Medical Center, Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogache, Driscoll Children's Hospital, Hannover Medical School, Jewish General Hospital, Kaiser Permanente, King Faisal Specialist Hospital & Research Center, Kingston Health Sciences Centre, Massachusetts General Hospital, McGill University Health Centre/Research Institute of the McGill University Health Centre, National Institutes of Health (NIH), Royal Perth Hospital, Princess Margaret Hospital for Children, Roswell Park Cancer Institute, The Hospital for Sick Children, St. Jude Children's Research Hospital, Huntsman Cancer Institute, University of Virginia, University of Texas Southwestern Medical Center, Ann & Robert H Lurie Children's Hospital of Chicago, Prisma Health-Upstate, Prisma Health-Midlands, Shaukat Khanum Memorial Cancer Hospital & Research Centre, Memorial Sloan Kettering Cancer Center, University of Colorado, Denver, Seattle Children's Hospital, CHU de Quebec-Universite Laval, Yale University, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Kaplan Medical Center, Schneider Children's Medical Center, Israel, Mayo Clinic, Children's Hospital Los Angeles, BC Cancer Foundation, Koc Healthcare Istanbul American Hospital, Marmara University Hospital
- Study start
- 6 Dec 2016 (actual)
- Primary completion
- 6 Dec 2031 (estimated)
- Study completion
- 6 Dec 2036 (estimated)
- First posted
- 22 Dec 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
PPB has strong genetic implications, with a unique set of conditions in an individual or their family, occurring mostly in childhood and adolescence. The International PPB/DICER1 Registry first reported DICER1 germline loss-of-function variations in individuals with PPB and their family members. Conditions associated with DICER1 include Sertoli-Leydig cell tumor (SLCT), gynandroblastoma, ovarian sarcoma, peritoneal PPB, lung cysts, renal cysts, cystic nephroma (CN), anaplastic sarcoma of the kidney (ASK), Wilms tumor, primary DICER1-associated central nervous system (CNS) sarcoma, pineoblastoma, pituitary blastoma, multinodular goiter, thyroid carcinoma, nasal chondromesenchymal hamartoma, ciliary body medulloepithelioma (CBME), juvenile hamartomatous intestinal polyps, embryonal rhabdomyosarcoma (ERMS) and undifferentiated sarcoma. DICER1 variations may also be associated with macrocephaly and overgrowth syndrome.
The International PPB/DICER1 Registry estimates that 30-50 cases of Type I and Ir PPB and 40-60 cases of Types II and III PPB are diagnosed annually worldwide. In 2009, the International Pleuropulmonary Blastoma Registry began a prospective study to collect treatment data on individuals for whom therapy decisions were made by their treating institution.
Detailed description
PPB is a rare cancer of the lung presenting in early childhood, mostly commonly from birth to age ~72 months. PPB occurs within the lung or between the lung and the chest wall. There are three primary forms of PPB called Types I, II, and III PPB. PPB is related to an underlying change/mutation in a gene called DICER1 which impacts gene expression and cell growth. DICER1 mutations may also lead to the development of other tumors in children and adults.
The International PPB/DICER1 Registry offers information based on previous data from Registry participants and the medical literature and collaborative efforts with international rare tumor groups.
Retrospective and real-time central pathology review is encouraged. Therapy decisions remain at the discretion of the treating institution.
Children with Type I PPB require surgery and sometimes chemotherapy. Therapy decisions are the responsibility of the treating institution. Surgical guidelines are presented. It is unknown whether adjuvant chemotherapy improves cure rates for Type I PPB patients. Chemotherapy options include a 22-week regimen: 4 courses of vincristine, actinomycin D and cyclophosphamide (VAC) followed by 3 courses of vincristine and actinomycin D (VA).
Children with Types II and III PPB, require surgery, chemotherapy and sometimes radiation therapy. Many children with Types II or III PPB receive a single-arm multi-agent chemotherapy neo-adjuvant/adjuvant regimen of IVADo (ifosfamide, vincristine, actinomycin, doxorubicin) for 36 weeks. Second and possible 3rd look surgery may be considered for local control. Radiation therapy may be considered.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Target follow-up
- 10 Years
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Type I PPB | – | –Type I PPB is an early manifestation of this malignant disease, cured in some cases by surgery. Surgical guidelines are presented. It is unknown whether adjuvant chemotherapy improves cure rates for individuals with Type I PPB. If the treating physicians select adjuvant chemotherapy treatment, chemotherapy options include a 22-week regimen: 4 courses of vincristine, actinomycin D and cyclophosphamide (VAC) followed by 3 courses of vincristine and actinomycin D (VA). Therapy decisions are the responsibility of the treating institution. |
| Types II and III PPB | – | –Types II and III PPB are aggressive sarcomas. Surgery and chemotherapy are necessary in all cases. Surgical guidelines are presented. Many children with Types II or III PPB receive a single-arm multi-agent chemotherapy neo-adjuvant/adjuvant regimen of IVADo (ifosfamide, vincristine, actinomycin, doxorubicin) for 36 weeks. Second and possible 3rd look surgery may be considered for local control. Radiation therapy may be considered. Specific therapy decisions are the responsibility of the treating institution. |
| Type Ir PPB | – | –Type Ir (regressed) PPB is a unique, purely cystic tumor which lacks a primitive cell component. The International PPB/DICER1 Registry will enroll and follow participants with Type Ir PPB, regardless of age. |
| DICER1 Gene or Cond Assoc with DICER1 | – | –The International PPB/DICER1 Registry for PPB, DICER1, and Associated Conditions study will enroll and follow participants who have DICER1 gene variants or conditions associated with DICER1. This could include Sertoli-Leydig cell tumor, cystic nephroma, thyroid nodules or carcinoma, intracranial sarcoma, and others. |
Who may qualify
- Ages
- 0 minutes to 100 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- 1. For those with PPB: PPB primarily affects children so their participation is required. 2. For those with DICER1-associated conditions: There's a wide array of conditions associated with DICER1, that occur at a variety of ages, from the development of cysts in utero, to lung cysts and thyroid disease noted in grandparents. 3. The Investigators are aware that many individuals with PPB, and with conditions associated with DICER1, come from countries outside of the U.S. To exclude individuals outside the US, minority groups and non-English speaking groups would be a disservice to eligible patients and healthcare providers and would limit the sample size of this rare cancer study.
Key inclusion criteria (5 listed)
- Known or suspected PPB or related thoracic tumor
- Known or suspected sex-cord stromal tumor including Sertoli-Leydig cell tumor and gynandroblastoma (males or females)
- Other known or suspected DICER1-related condition including ovarian sarcoma, cystic nephroma, renal sarcoma, pineoblastoma, pituitary blastoma, nasal chondromesenchymal hamartoma, ciliary body medulloepithelioma and others
- Individuals with known or suspected DICER1 pathogenic variation regardless of whether they have an established DICER1-associated condition
- Informed consent by patient/ or parent/guardian (also, where appropriate: assent and HIPAA consent)
Key exclusion criteria (1 listed)
- Absence of appropriate consent for Registry participation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Event-free survival
Time frame: 7 years
The primary endpoint for statistical analysis will be time from start treatment to an event, defined as the occurrence of progression or recurrence of PPB, occurrence of a second malignant neoplasm, or death from any cause that is at least possibly related to the original disease or treatment.
6 secondary outcomes
Overall response to chemotherapy
Time frame: 7 years
Overall survival
Time frame: 7 years
Quality of life outcomes in individuals diagnosed with PPB.
Time frame: 7 years
Cardiac outcomes in individuals diagnosed with PPB.
Time frame: 7 years
Pulmonary function testing results in individuals diagnosed with PPB
Time frame: 7 years
Incidence of neoplasms in individuals with DICER1-related conditions or germline DICER1 variants. mutation.
Time frame: 7 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2026.
- Background: PubMed 33158809Vasta LM, McMaster ML, Harney LA, Ling A, Kim J, Harris AK, Carr AG, Damrauer SM, Rader DJ, Kember RL, Kanetsky PA, Nathanson KL, Pyle LC, Greene MH, Schultz KA, Stewart DR; Regeneron Genetics Center (RGC) Research Team. Lack of pathogenic germline DICER1 variants in males with testicular germ-cell tumors. Cancer Genet. 2020 Oct;248-249:49-56. doi: 10.1016/j.cancergen.2020.10.002. Epub 2020 Oct 24.
- Background: PubMed 33826235Bisogno G, Sarnacki S, Stachowicz-Stencel T, Minard Colin V, Ferrari A, Godzinski J, Gauthier Villars M, Bien E, Hameury F, Helfre S, Schneider DT, Reguerre Y, Lopez Almaraz R, Janic D, Cesen M, Kolenova A, Rascon J, Martinova K, Cosnarovici R, Pourtsidis A, Ben Ami T, Roganovic J, Koscielniak E, Schultz KAP, Brecht IB, Orbach D. Pleuropulmonary blastoma in children and adolescents: The EXPeRT/PARTNER diagnostic and therapeutic recommendations. Pediatr Blood Cancer. 2021 Jun;68 Suppl 4(Suppl 4):e29045. doi: 10.1002/pbc.29045. Epub 2021 Apr 7.
- Background: PubMed 33760357Schneider DT, Orbach D, Ben-Ami T, Bien E, Bisogno G, Brecht IB, Cecchetto G, Ferrari A, Godzinski J, Janic D, Lopez Almaraz R, Pourtsidis A, Roganovic J, Schultz KAP, Stachowicz-Stencel T, Fresneau B. Consensus recommendations from the EXPeRT/PARTNER groups for the diagnosis and therapy of sex cord stromal tumors in children and adolescents. Pediatr Blood Cancer. 2021 Jun;68 Suppl 4:e29017. doi: 10.1002/pbc.29017. Epub 2021 Mar 24.
- Background: PubMed 33258270Ferguson MJ, Ivanovich J, Stansell P, Vik TA, Helvie AE, Schmitt MR, Schultz KA, Dehner LP, Renbarger JL, Marshall MS. Previously unreported somatic variants in two patients with pleuropulmonary blastoma with metastatic brain recurrence. Pediatr Blood Cancer. 2021 May;68(5):e28825. doi: 10.1002/pbc.28825. Epub 2020 Nov 30. No abstract available.
- Background: PubMed 33209717Schneider KW, Cost NG, Schultz KAP, Svihovec S, Suttman A. Germline predisposition to genitourinary rhabdomyosarcoma. Transl Androl Urol. 2020 Oct;9(5):2430-2440. doi: 10.21037/tau-20-76.
- Background: PubMed 28620008Schultz KAP, Rednam SP, Kamihara J, Doros L, Achatz MI, Wasserman JD, Diller LR, Brugieres L, Druker H, Schneider KA, McGee RB, Foulkes WD. PTEN, DICER1, FH, and Their Associated Tumor Susceptibility Syndromes: Clinical Features, Genetics, and Surveillance Recommendations in Childhood. Clin Cancer Res. 2017 Jun 15;23(12):e76-e82. doi: 10.1158/1078-0432.CCR-17-0629.
- Background: PubMed 24761742Schultz KAP, Nelson AT, Kamihara J, Bauer AJ, Hatton J, Merideth MA, Stratton P, Harris AK, Field A, Dehner LP, Stewart DR, Hill DA, Messinger YH. DICER1-Related Tumor Predisposition. 2014 Apr 24 [updated 2026 Mar 25]. In: Adam MP, Bick S, Mirzaa GM, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK196157/
- Background: PubMed 34599283Gonzalez IA, Stewart DR, Schultz KAP, Field AP, Hill DA, Dehner LP. DICER1 tumor predisposition syndrome: an evolving story initiated with the pleuropulmonary blastoma. Mod Pathol. 2022 Jan;35(1):4-22. doi: 10.1038/s41379-021-00905-8. Epub 2021 Oct 1.
- Background: PubMed 34398502Terry W, Carlisle EM, Mallinger P, Nelson AT, Gordon D, Messinger YH, Field A, Dehner LP, Hill DA, Schultz KAP. Thoracic Sertoli-Leydig cell tumor: An alternative type of pleuropulmonary blastoma associated with DICER1 variation. Pediatr Blood Cancer. 2021 Nov;68(11):e29284. doi: 10.1002/pbc.29284. Epub 2021 Aug 16.
- Results publication: PubMed 19556464Hill DA, Ivanovich J, Priest JR, Gurnett CA, Dehner LP, Desruisseau D, Jarzembowski JA, Wikenheiser-Brokamp KA, Suarez BK, Whelan AJ, Williams G, Bracamontes D, Messinger Y, Goodfellow PJ. DICER1 mutations in familial pleuropulmonary blastoma. Science. 2009 Aug 21;325(5943):965. doi: 10.1126/science.1174334. Epub 2009 Jun 25.
- Results publication: PubMed 25209242Messinger YH, Stewart DR, Priest JR, Williams GM, Harris AK, Schultz KA, Yang J, Doros L, Rosenberg PS, Hill DA, Dehner LP. Pleuropulmonary blastoma: a report on 350 central pathology-confirmed pleuropulmonary blastoma cases by the International Pleuropulmonary Blastoma Registry. Cancer. 2015 Jan 15;121(2):276-85. doi: 10.1002/cncr.29032. Epub 2014 Sep 10.
- Results publication: PubMed 33484847Kebudi R, Dural O, Bay SB, Gorgun O, Onder S, Bilgic B, Yilmaz I, Iribas A, Arndt CA, Harris AK, Field A, Schultz KAP, Hill DA. Childhood Rhabdomyosarcoma of the Female Genital Tract: Association with Pathogenic DICER1 Variation, Clinicopathological Features, and Outcomes. J Pediatr Adolesc Gynecol. 2021 Aug;34(4):449-453. doi: 10.1016/j.jpag.2021.01.011. Epub 2021 Jan 20.
- International Pleuropulmonary Blastoma (PPB)/DICER1 Registry web siteLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Pleuropulmonary Blastoma
Not yet recruitingObservational study
Clinical Genetics Branch Eligibility Screening Survey
Melanoma, Li-Fraumeni Syndrome
Active, not recruiting
International Pleuropulmonary Blastoma (PPB) Treatment and Biology Registry
Pleuropulmonary Blastoma
RecruitingObservational study
DICER1-related Pleuropulmonary Blastoma Cancer Predisposition Syndrome: A Natural History Study
Pleuropulmonary Blastoma, Cystic Nephroma
RecruitingPhase 3
Testing a Standardized Approach to Surgery and Chemotherapy for Type I Pleuropulmonary Blastoma or the Addition of an Anti-cancer Drug, Topotecan, to the Usual Treatment for Types II and III Pleuropulmonary Blastoma
Pleuropulmonary Blastoma
RecruitingObservational study
An International Study on Pediatric Patients With Rare Tumors.
Paraganglioma/ Phaeochromocytoma, Melanoma and Other Malignant Neoplasms of Skin
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.
Kris Ann P Schultz, MD principal investigator
Children's Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pleuropulmonary Blastoma and Sertoli-Leydig Cell Tumor, run by Children's Hospitals and Clinics of Minnesota at 1 site 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 5 inclusion and 1 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: looking for participants now, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kris Ann P Schultz, MD (612-813-7121, krisann.schultz@childrensmn.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event-free survival (time frame: 7 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03382158, which also lists 33 linked publications.
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 26 Oct 2026.