DICER1-related Pleuropulmonary Blastoma Cancer Predisposition Syndrome: A Natural History Study

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01247597
First received: November 23, 2010
Last updated: May 15, 2014
Last verified: April 2014
  Purpose

Background:

- Pleuropulmonary blastoma (PPB) is a rare fast-growing lung tumor that is associated with other, rare tumor types. Most cases of PPB appear in children younger than 6 years of age. Recently, it has been shown that this condition can be inherited (e.g., mutation of the DICER1 gene). Researchers are studying both clinical and genetic aspects of this newly described condition. They are interested in collecting further medical history and genetic information on individuals and close relatives of individuals who have PPB or other rare associated tumors.

Objectives:

- To study individuals with a personal or a family history of pleuropulmonary blastoma (PPB) or other rare tumors that can be associated with PPB (e.g., cystic nephroma, nasal chondromesenchymal hamartoma, ovarian Sertoli-Leydig cell tumors, ocular medulloepithelioma).

Eligibility:

  • Individuals who have been diagnosed with PPB and/or PPB-related tumors.
  • Close blood relatives (e.g., parents, siblings, grandparents) of individuals who have been diagnosed with PPB and/or PPB-related tumors.

Design:

  • Interested participants can enroll or inquire about this study by calling 1-800-518-8474.
  • Participants will be asked to complete family history and medical history questionnaires. They will complete the questionnaire if they are at least 18 years of age, or another person will complete the questionnaire if the key family member is too young to do so on his or her own.
  • Participants will be asked to sign a medical record release form to allow researchers to examine detailed medical history information.
  • Participants may be asked to have a physical examination and imaging studies, provide blood and saliva samples, or provide tumor tissue from prior biopsies or cancer surgeries.
  • Annually, participants will update the family history and individual information questionnaires to document important changes in medical history, and will also update the medical record release form. Participants may be asked to provide additional cheek lining cells and/or blood samples, as well as tumor tissue from any new or planned biopsies or tumor surgeries.
  • Treatment will not be provided as part of this protocol.

Condition
Pleuropulmonary Blastoma
Cystic Nephroma
Ovarian Sertoli-Leydig Cell Tumors
Ocular Medulloepithelioma
Nasal Chondromesenchymal Hamartoma

Study Type: Observational
Official Title: Dicer1-Related Pleuropulmonary Blastoma Cancer Predisposition Syndrome: A Natural History Study

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • 2. To characterize the clinical phenotype of, and study the incident and prevalent cancer rates in, these patients and their family members, for all cancers combined, and for each type of cancer, and to identify and confirm the specific types of... [ Time Frame: Ongoing ] [ Designated as safety issue: No ]
  • 1. To establish a cohort of patients with PPB and/or specific neoplasms of the PPB spectrum (cystic nephroma, nasal chondromesenchymal hamartoma, ovarian Sertoli-Leydig cell and other sex cord-stromal tumors, ocular medulloepithelioma, Wilms tum... [ Time Frame: Ongoing ] [ Designated as safety issue: No ]
  • 3. To identify differences between patients with a germline mutation in DICER1 (or another gene(s) from this pathway) who do develop cancer and those who do not develop cancer. These differences may include genotype/phenotype/cancer susceptibili... [ Time Frame: Ongoing ] [ Designated as safety issue: No ]
  • 4. To develop evidence-based management guidelines for cancer prevention and risk-reduction strategies for PPB patients and their family members prior to and after obtaining answers to the questions/objectives above. [ Time Frame: Ongoing ] [ Designated as safety issue: No ]
  • 5. To evaluate various parameters related to psychosocial and behavioral issues resulting from being a member of a family at increased risk of PPB. [ Time Frame: Ongoing ] [ Designated as safety issue: No ]
  • 6. To create a biospecimen repository of carefully-annotated tissue samples for use in subsequent etiologically-oriented translational research projects. These samples comprise an invaluable resource for current and future studies related to the... [ Time Frame: Ongoing ] [ Designated as safety issue: No ]

Estimated Enrollment: 1500
Study Start Date: November 2010
Detailed Description:

Background:

In 2009, Hill and colleagues identified heterozygous germline mutations in DICER1 in patients with familial pleuropulmonary blastoma (PPB) 1. This disorder represents the first reported cancer predisposition syndrome that is due to altered microRNA biogenesis.

Primary Objectives:

  1. To establish a cohort of patients with PPB and/or specific neoplasms of the PPB spectrum (cystic nephroma, nasal chondromesenchymal hamartoma, ovarian Sertoli-Leydig cell tumors, ocular medulloepithelioma, others to be defined), in order to determine the frequency of DICER1 germline mutations in these patients and their family members.
  2. To characterize the clinical phenotype of, and study the incident and prevalent cancer rates in, these patients and their family members.
  3. To identify differences between patients with a mutation in DICER1 who do develop cancer and those who do not develop cancer.
  4. To develop evidence-based management guidelines for PPB patients and their family.
  5. To evaluate various parameters related to psychosocial and behavioral issues resulting from being a member of a family at increased risk of PPB.
  6. Create a biospecimen repository of carefully-annotated tissue samples for use in subsequent etiologically-oriented translational research projects.

Eligibility:

  • Individuals with PPB and their relatives.
  • Individuals in the general population with one or more of the unique tumors reported in patients and families with PPB: cystic nephroma, ovarian Sertoli-Leydig cell tumors, ocular medulloepithelioma, and nasal chondromesenchymal hamartoma. Relatives of these patients will be eligible for study enrollment as well.

Design:

Multidisciplinary natural history study with self-administered questionnaires, clinical/epidemiologic/genetic evaluations, clinical and research laboratory tests, review of medical records, cancer surveillance, and biospecimen acquisition:

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:
  • Patients with histologically-confirmed PPB and their relatives of interest [parents, siblings, mutation carriers (e.g., grandparents), other affecteds]. Given the rarity of this disorder, we are open to patients from all over the world, at the discretion of the PI (e.g. availability of medical recors in English, ability of patient/family to communicate in English) but will follow NIH travel regulations.
  • Patients from the general population with one or more of the unique tumors of the types seen in patients/families with PPB - cystic nephroma, ovarian Sertoli-Leydig cell and other sex cord-stromal tumors, ocular medulloepithelioma, nasal chondromesenchymal hamartoma. Wilms tumor, embryonal rhabdomyosarcoma, pineoblastoma - regardless of family history. Relatives of these patients will be eligible for study as well (parents, siblings, mutation carriers, other affecteds). Additional syndrome-associated neoplasms may be identified in the future, and they will be added to the protocol as needed.
  • All types and amounts of prior therapies are allowed.
  • There is no age restriction.
  • There is no restriction related to organ and marrow function.
  • Ability of the proband or their guardians to understand, and their willingness to sign, a written informed consent document.

EXCLUSION CRITERIA:

  • Individuals and families referred for evaluation in whom reported diagnoses are not verifiable.
  • Inability to provide informed consent.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01247597

Contacts
Contact: Douglas R Stewart, M.D. (240) 276-7238 drstewart@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    (888) NCI-1937      
Sponsors and Collaborators
Investigators
Principal Investigator: Douglas R Stewart, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT01247597     History of Changes
Other Study ID Numbers: 110034, 11-C-0034
Study First Received: November 23, 2010
Last Updated: May 15, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Thyroid Cancer
Germline DICER1 Mutation
MicroRNA Biogenesis
Pleuropulmonary Blastoma
PPB

Additional relevant MeSH terms:
Sertoli-Leydig Cell Tumor
Disease Susceptibility
Hamartoma
Leydig Cell Tumor
Neuroectodermal Tumors, Primitive
Pulmonary Blastoma
Sex Cord-Gonadal Stromal Tumors
Neoplasms, Gonadal Tissue
Neoplasms by Histologic Type
Neoplasms
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Testicular Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Genital Diseases, Male
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Endocrine System Diseases
Gonadal Disorders
Testicular Diseases
Disease Attributes
Pathologic Processes
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on August 21, 2014