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International PPB Registry for PPB, DICER1 and Associated Conditions

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ClinicalTrials.gov Identifier: NCT03382158
Recruitment Status : Recruiting
First Posted : December 22, 2017
Last Update Posted : December 22, 2017
Sponsor:
Collaborators:
Children's Research Institute
Washington University School of Medicine
Information provided by (Responsible Party):
Children's Hospitals and Clinics of Minnesota

Brief Summary:
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.

Condition or disease
Pleuropulmonary Blastoma Sertoli-Leydig Cell Tumor DICER1 Syndrome Cystic Nephroma Wilms Tumor Pineoblastoma Renal Sarcoma Nodular Hyperplasia of Thyroid Nasal Chondromesenchymal Hamartoma Ciliary Body Medulloepithelioma Neuroblastoma Pituitary Cancer Embryonal Rhabdomyosarcoma

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 Registry offers information based on previous data from Registry participants and the medical literature and collaborative efforts with international rare tumor groups.

Retrospective central pathology review is required. 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.


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Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: International Pleuropulmonary Blastoma Registry for PPB, DICER1 and Associated Conditions
Actual Study Start Date : December 6, 2016
Estimated Primary Completion Date : December 6, 2023
Estimated Study Completion Date : December 6, 2026


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 Registry for PPB, DICER1 and Associated Conditions 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 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.



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. Overall survival [ Time Frame: 7 years ]
    The investigators will assess overall survival and time to death from any cause among participants.

  3. 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 including treatment, germline DICER1 mutations and familial cancer 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.

  4. 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.

  5. 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 (FVC, FEV1/FVC) with DICER1-related tumors, and compare outcomes to those with more common childhood cancers.

  6. 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


Biospecimen Retention:   Samples With DNA
Tumor tissue, blood, urine, and cerebral spinal fluid (the latter only if a lumbar puncture is performed for clinical purposes)


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
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. The chemotherapy regimens included as guidance have been used in children before, the toxicity is acceptable, well known and reported.
  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 not include minority groups and non-English speaking groups would severely limit the sample size of this study, and may do a disservice to eligible patients and healthcare providers.
Criteria

Inclusion Criteria:

  1. Pathology Diagnosis: Individuals with newly-diagnosed PPB Types I, II or III. Diagnosis is made by the local pathologist.

    All cases must be submitted for central pathology review. Only centrally-reviewed cases confirmed as PPB will be analyzed prospectively.

    Cases in which the initial diagnosis is "suggestive" or "supportive" of PPB, but not diagnostic, and in which later resection specimens, including resections following chemotherapy, confirm a PPB diagnosis will be included. Patients diagnosed by fine needle aspiration biopsy will be included only if a later resection specimen, including resection(s) following chemotherapy, is diagnostic of PPB.

  2. Prior Therapy: PPB Type I: All patients are eligible and will be followed in the study.
  3. PPB Types II or III: Newly-diagnosed Types II and III PPB patients will be included in the Treatment and Biology Registry.
  4. Prior corticosteroid therapy is allowed.
  5. Types II and III PPB patients with PRIOR Type I PPB diagnosis
  6. Individuals with DICER1-related conditions including PPB, Sertoli-Leydig cell tumor, gynandroblastoma, cystic nephroma, renal sarcoma and others.
  7. Individuals with the DICER1 gene mutation regardless of whether they have a known DICER1-associated condition
  8. Informed consent by patient/ or parent/guardian (also, where appropriate: assent and HIPAA consent)

Exclusion Criteria:

-


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03382158


Contacts
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Contact: Kris Ann P Schultz, MD 612-813-7121 krisann.schultz@childrensmn.org
Contact: Gretchen M Williams, BS 612-813-7115 gretchen.williams@childrensmn.org

Locations
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United States, Minnesota
Children;s Minnesota Recruiting
Minneapolis, Minnesota, United States, 55404
Contact: Gretchen Williams, BS    612-813-7115    gretchen.williams@childrensmn.org   
Sponsors and Collaborators
Children's Hospitals and Clinics of Minnesota
Children's Research Institute
Washington University School of Medicine
Investigators
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Principal Investigator: Kris Ann P Schultz, MD Children's Minnesota
  Study Documents (Full-Text)

Documents provided by Children's Hospitals and Clinics of Minnesota:
Study Protocol  [PDF] August 24, 2017
Statistical Analysis Plan  [PDF] October 20, 2016


Additional Information:
Publications of Results:
Other Publications:
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Responsible Party: Children's Hospitals and Clinics of Minnesota
ClinicalTrials.gov Identifier: NCT03382158     History of Changes
Other Study ID Numbers: FDAAA
First Posted: December 22, 2017    Key Record Dates
Last Update Posted: December 22, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Children's Hospitals and Clinics of Minnesota:
pleuropulmonary blastoma
PPB
DICER1
Sertoli-Leydig cell tumor
cystic nephroma

Additional relevant MeSH terms:
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Neoplasms
Neuroblastoma
Hyperplasia
Rhabdomyosarcoma
Wilms Tumor
Pinealoma
Pulmonary Blastoma
Neuroectodermal Tumors, Primitive
Hamartoma
Rhabdomyosarcoma, Embryonal
Leydig Cell Tumor
Sertoli-Leydig Cell Tumor
Goiter, Nodular
Pituitary Neoplasms
Neuroectodermal Tumors, Primitive, Peripheral
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Pathologic Processes
Myosarcoma
Neoplasms, Muscle Tissue
Neoplasms, Connective and Soft Tissue
Sarcoma
Neoplasms, Complex and Mixed
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms