International PPB/DICER1 Registry

February 7, 2024 updated by: Children's Hospitals and Clinics of Minnesota

International Pleuropulmonary Blastoma/DICER1 Registry (for PPB, DICER1 and Associated Conditions)

Pleuropulmonary blastoma (PPB) is a rare malignant neoplasm of the lung presenting in early childhood. Type I PPB is a purely cystic lesion, Type II is a partially cystic, partially solid tumor, Type III is a completely solid tumor. Treatment of children with PPB is at the discretion of the treating institution. This study builds off of the 2009 study and will also seek to enroll individuals with DICER1-associated conditions, some of whom may present only with the DICER1 gene mutation, which will help the Registry understand how these tumors and conditions develop, their clinical course and the most effective treatments.

Study Overview

Status

Recruiting

Conditions

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 Type

Observational

Enrollment (Estimated)

3400

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

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.

Description

Inclusion Criteria:

  1. Known or suspected PPB or related thoracic tumor
  2. Known or suspected sex-cord stromal tumor including Sertoli-Leydig cell tumor and gynandroblastoma (males or females)
  3. 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
  4. Individuals with known or suspected DICER1 pathogenic variation regardless of whether they have an established DICER1-associated condition
  5. Informed consent by patient/ or parent/guardian (also, where appropriate: assent and HIPAA consent)

Exclusion criteria:

Absence of appropriate consent for Registry participation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Other

Cohorts and Interventions

Group / Cohort
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
PPB and the associated conditions found in PPB families suggest a familial tendency to formation of tumors. The International PPB/DICER1 Registry for PPB, DICER1 and Associated Conditions study will enroll and follow participants who have the DICER1 gene mutations or conditions associated with PPB or DICER1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
7 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall response to chemotherapy
Time Frame: 7 years
The investigators will assess overall response to chemotherapy among participants with radiographically measurable tumor following initial surgery or biopsy.
7 years
Overall survival
Time Frame: 7 years
The investigators will assess overall survival and time to death from any cause among participants.
7 years
Quality of life outcomes in individuals diagnosed with PPB.
Time Frame: 7 years
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.
7 years
Cardiac outcomes in individuals diagnosed with PPB.
Time Frame: 7 years
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.
7 years
Pulmonary function testing results in individuals diagnosed with PPB
Time Frame: 7 years
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.
7 years
Incidence of neoplasms in individuals with DICER1-related conditions or germline DICER1 variants. mutation.
Time Frame: 7 years
This protocol will include individuals with germline DICER1 mutations and will calculate incidence rates of specific neoplasms in this population
7 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Hospitals and Clinics of Minnesota

Collaborators

M.D. Anderson Cancer Center
Washington University School of Medicine
Dana-Farber Cancer Institute
Emory University
University of California, San Francisco
Ann & Robert H Lurie Children's Hospital of Chicago
University of Texas
Kaiser Permanente
University of Cambridge
KK Women's and Children's Hospital
Children's Healthcare of Atlanta
Phoenix Children's Hospital
Beijing Children's Hospital
Akron Children's Hospital
Allina Health System
Louisiana State University Health Sciences Center Shreveport
Starship Children's Hospital of New Zealand
Dayton Children's Hospital
ResourcePath, LLC
UC Davis Children's Hospital

Investigators

  • Principal Investigator: Kris Ann P Schultz, MD, Children's Minnesota

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 6, 2016

Primary Completion (Estimated)

December 6, 2030

Study Completion (Estimated)

December 6, 2035

Study Registration Dates

First Submitted

October 11, 2017

First Submitted That Met QC Criteria

December 18, 2017

First Posted (Actual)

December 22, 2017

Study Record Updates

Last Update Posted (Actual)

February 8, 2024

Last Update Submitted That Met QC Criteria

February 7, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FDAAA

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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