International Ovarian & Testicular Stromal Tumor Registry

Ovarian Sex-cord Stromal Tumor Clinical Trial

— OTST  

Official title:

International Ovarian & Testicular Stromal Tumor Registry

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01970696
• Other study ID #: International OTST Registry
• Status: Recruiting
• Start date: December 8, 2011
• Est. completion date: December 2030

Study information

• Verified date: March 2023
• Source: Children's Hospitals and Clinics of Minnesota
• Contact: Anne Harris, MPH
• Phone: 612-813-5861
• Email: anne.harris[@]childrensmn.org
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Rare tumors are understudied, yet have the potential to shed light on vast areas of cancer research. Ovarian sex cord-stromal tumors, rare tumors of childhood and young adulthood, have recently been found to be associated with a lung cancer of early childhood called pleuropulmonary blastoma (PPB). The cause of these ovarian tumors is unknown. DICER1 mutations are seen in the majority of children with PPB. Research shows DICER1 mutations are also seen in some patients with ovarian tumors. Like PPB, ovarian stromal tumors are highly curable when found in early stage; however, later forms of the disease are aggressive and often fatal. The International Ovarian Stromal Tumor Registry collects clinical and biologic data to understand why these tumors occur and how to treat them. Current work involves the study of the role of DICER1 and miRNA expression in ovarian stromal tumors. Understanding the clinical history, predisposing factors and DICER1 and miRNA expression in these ovarian tumors of childhood will lead to targeted screening and risk stratification for evidence-based treatment and biologically rational therapies. These efforts will improve the lives of children by increasing survival and reducing late effects.

The specific goals of the International Ovarian and Testicular Stromal Tumor Registry are:

1. to understand risk factors by studying age, pathologic subtype, histopathologic features, tumor invasiveness, degree of differentiation, presence of metastasis

2. to collect information on personal and family history in order to refine the clinical characteristics of patients and families with and without germline DICER1 mutations and other genetic predisposing factors

3. to determine whether there is a pattern of gene expression or DNA alterations that correlate with predisposition to ovarian tumors, biologic behavior and clinical outcome

4. to determine optimal screening regimens

5. to use clinical data obtained through the Registry to refine treatment algorithms

6. to establish a collection of annotated biology specimens (tumor tissue and germline DNA) for future research

Description:

The Registry collects and analyzes case-by-case data on ovarian and testicular stromal tumors. Cases are identified:

1. by referrals from clinicians or pathologists

2. by families initiating contact with the Registry

3. by Registry requests to authors of published cases to share further details

The data collected include:

1. clinical and laboratory findings

2. family history

3. imaging studies

4. surgery records

5. pathology records including review and study of pathology materials

6. treatment (surgery, chemotherapy, radiation)

7. recurrences or metastases

8. long-term follow-up

The demographic and clinical data are abstracted into a database secured by password protection. Each record in the database has a unique Registry number.

Enrollment in the OTST Registry is based on local diagnosis, but central pathology review is offered as a part of Registry procedures.

For each patient enrolled, the Registry will request 1) whole blood for DNA extraction and lymphoblastoid cell line generation 2) slides or snap frozen tumor tissue (if available), 3) paraffin blocks and/or scrolls and 4) fresh tissue. In some cases, saliva samples, buccal swabs or urine samples will be obtained for DNA extraction.

Pathology materials are centrally reviewed when available. Any discrepancies in the diagnostic interpretation are discussed with the submitting pathologist or clinician. When the central review pathologist cannot confirm diagnosis of a stromal tumor, the referring physician is notified. The local pathologist retains responsibility for the final pathological diagnosis. It is the responsibility of the referring physician to notify the patient regarding any discrepancy found.

Biologic specimens will be banked and stored for future research.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 2030
• Est. primary completion date: December 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 0 Years to 100 Years

Eligibility

Inclusion Criteria:

• Previous or current diagnosis of an ovarian sex cord stromal including but not limited to: Sertoli-Leydig cell tumor, gynandroblastoma (now enrolling these patients on PPB/DICER1 Registry), juvenile granulosa cell tumor, Sertoli cell tumor, sex cord-stromal tumor with annular tubules or undifferentiated stromal tumor

• Previous or current diagnosis of a testicular stromal tumor including but not limited to: juvenile granulosa cell tumor, Sertoli cell tumor, Leydig cell tumor or undifferentiated stromal tumor

Exclusion Criteria:

• Unable to provide informed consent/assent

• Adult Granulosa cell tumor (unless otherwise specified by Medical Director)

Related Conditions & MeSH terms

• Carcinoma, Small Cell
• Neoplasms
• Ovarian Sex-cord Stromal Tumor
• Ovarian Small Cell Carcinoma
• Small Cell Lung Carcinoma
• Testicular Stromal Tumors

Locations

Country	Name	City	State
United States	Children's Minnesota	Minneapolis	Minnesota

Sponsors (14)

Lead Sponsor

Collaborator

Children's Hospitals and Clinics of Minnesota

Allina Health System, Children's Hospital Colorado, Children's National Research Institute, Dana-Farber Cancer Institute, Klinikum Dortmund Wirbelsäulenchirurgie, M.D. Anderson Cancer Center, Massachusetts General Hospital, Phoenix Children's Hospital, ResourcePath, LLC, Rutgers University, University of Cambridge, University of Texas Southwestern Medical Center, Washington University School of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (26)

Doros L, Yang J, Dehner L, Rossi CT, Skiver K, Jarzembowski JA, Messinger Y, Schultz KA, Williams G, Andre N, Hill DA. DICER1 mutations in embryonal rhabdomyosarcomas from children with and without familial PPB-tumor predisposition syndrome. Pediatr Blood — View Citation

Dural O, Kebudi R, Yavuz E, Yilmaz I, Buyukkapu Bay S, Schultz KAP, Hill DA. DICER1-Related Embryonal Rhabdomyosarcoma of the Uterine Corpus in a Prepubertal Girl. J Pediatr Adolesc Gynecol. 2020 Apr;33(2):173-176. doi: 10.1016/j.jpag.2019.12.002. Epub 20 — View Citation

Golmard 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 — View Citation

Kebudi 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 Featu — View Citation

Merideth MA, Harney LA, Vyas N, Bachi A, Carr AG, Hill DA, Dehner LP, Schultz KAP, Stewart DR, Stratton P. Gynecologic and reproductive health in patients with pathogenic germline variants in DICER1. Gynecol Oncol. 2020 Mar;156(3):647-653. doi: 10.1016/j. — View Citation

Pappo AS, Furman WL, Schultz KA, Ferrari A, Helman L, Krailo MD. Rare Tumors in Children: Progress Through Collaboration. J Clin Oncol. 2015 Sep 20;33(27):3047-54. doi: 10.1200/JCO.2014.59.3632. Epub 2015 Aug 24. — View Citation

Pashankar F, Bisogno G, Ribeiro R, Messinger Y, Schultz KA, Rodriguez-Galindo C. The role of registries and tumor banking in rare pediatric tumors. Curr Pediatr Rep 2015:1-9. Avail online 15 Mar 2015. DOI 10.1007/s40124-015-0077-9.

Rio Frio T, Bahubeshi A, Kanellopoulou C, Hamel N, Niedziela M, Sabbaghian N, Pouchet C, Gilbert L, O'Brien PK, Serfas K, Broderick P, Houlston RS, Lesueur F, Bonora E, Muljo S, Schimke RN, Bouron-Dal Soglio D, Arseneau J, Schultz KA, Priest JR, Nguyen VH, Harach HR, Livingston DM, Foulkes WD, Tischkowitz M. DICER1 mutations in familial multinodular goiter with and without ovarian Sertoli-Leydig cell tumors. JAMA. 2011 Jan 5;305(1):68-77. doi: 10.1001/jama.2010.1910. — View Citation

Rove KO, Maroni PD, Cost CR, Fairclough DL, Giannarini G, Harris AK, Schultz KA, Cost NG. Pathologic Risk Factors for Metastatic Disease in Postpubertal Patients With Clinical Stage I Testicular Stromal Tumors. Urology. 2016 Nov;97:138-144. doi: 10.1016/j — View Citation

Rove KO, Maroni PD, Cost CR, Fairclough DL, Giannarini G, Harris AK, Schultz KA, Cost NG. Pathologic Risk Factors in Pediatric and Adolescent Patients With Clinical Stage I Testicular Stromal Tumors. J Pediatr Hematol Oncol. 2015 Nov;37(8):e441-6. doi: 10 — View Citation

Rutter MM, Jha P, Schultz KA, Sheil A, Harris AK, Bauer AJ, Field AL, Geller J, Hill DA. DICER1 Mutations and Differentiated Thyroid Carcinoma: Evidence of a Direct Association. J Clin Endocrinol Metab. 2016 Jan;101(1):1-5. doi: 10.1210/jc.2015-2169. Epub — View Citation

Schneider 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. — View Citation

Schneider 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. — View Citation

Schultz KA, Harris A, Messinger Y, Sencer S, Baldinger S, Dehner LP, Hill DA. Ovarian tumors related to intronic mutations in DICER1: a report from the international ovarian and testicular stromal tumor registry. Fam Cancer. 2016 Jan;15(1):105-10. doi: 10 — View Citation

Schultz KA, Harris A, Williams GM, Baldinger S, Doros L, Valusek P, Frazier AL, Dehner LP, Messinger Y, Hill DA. Judicious DICER1 testing and surveillance imaging facilitates early diagnosis and cure of pleuropulmonary blastoma. Pediatr Blood Cancer. 2014 — View Citation

Schultz KA, Harris AK, Schneider DT, Young RH, Brown J, Gershenson DM, Dehner LP, Hill DA, Messinger YH, Frazier AL. Ovarian Sex Cord-Stromal Tumors. J Oncol Pract. 2016 Oct;12(10):940-946. doi: 10.1200/JOP.2016.016261. — View Citation

Schultz KA, Ness KK, Nagarajan R, Steiner ME. Adnexal masses in infancy and childhood. Clin Obstet Gynecol. 2006 Sep;49(3):464-79. doi: 10.1097/00003081-200609000-00007. — View Citation

Schultz KA, Pacheco MC, Yang J, Williams GM, Messinger Y, Hill DA, Dehner LP, Priest JR. Ovarian sex cord-stromal tumors, pleuropulmonary blastoma and DICER1 mutations: a report from the International Pleuropulmonary Blastoma Registry. Gynecol Oncol. 2011 — View Citation

Schultz KA, Schneider DT, Pashankar F, Ross J, Frazier L. Management of ovarian and testicular sex cord-stromal tumors in children and adolescents. J Pediatr Hematol Oncol. 2012 May;34 Suppl 2:S55-63. doi: 10.1097/MPH.0b013e31824e3867. — View Citation

Schultz KA, Sencer SF, Messinger Y, Neglia JP, Steiner ME. Pediatric ovarian tumors: a review of 67 cases. Pediatr Blood Cancer. 2005 Feb;44(2):167-73. doi: 10.1002/pbc.20233. — View Citation

Schultz KAP and Miller R. (2014) Adnexal Masses in Infancy and Childhood. Coomarasamy A, Davuka W, Shafi M, Chan C (eds): Gynecology and Obstetric Surgery: Challenges and Management Options. Wiley-Blackwell. [BOOK.] [In press; avail may 2015].

Schultz KAP, Frazier L, Schneider DT. (2014) Ovarian and Testicular Sex Cord Stromal Tumors. Frazier, AL, Amatruda JF (eds): Textbook Pediatric Germ Cell Tumors, Pediatric Oncology 1. Berlin Heidelberg. Springer-Verlag. [BOOK.].

Schultz KAP, Harris AK, Finch M, Dehner LP, Brown JB, Gershenson DM, Young RH, Field A, Yu W, Turner J, Cost NG, Schneider DT, Stewart DR, Frazier AL, Messinger Y, Hill DA. DICER1-related Sertoli-Leydig cell tumor and gynandroblastoma: Clinical and geneti — View Citation

Schultz KAP, Stewart DR, Kamihara J, Bauer AJ, Merideth MA, Stratton P, Huryn LA, Harris AK, Doros L, Field A, Carr AG, Dehner LP, Messinger Y, Hill DA. DICER1 Tumor Predisposition. 2014 Apr 24 [updated 2020 Apr 30]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from http://www.ncbi.nlm.nih.gov/books/NBK196157/ — View Citation

Terry 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. 202 — View Citation

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 — View Citation

* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	DICER1 mutations in ovarian and testicular stromal tumors	We will analyze germline DNA from patients with gonadal stromal tumors to determine the presence of DICER1 mutations. The tumor tissue will also be sequenced. mRNA and miRNA expression will be analyzed on tumor tissue. Results of the above will be correlated with clinical outcome.	3 years
Secondary	Clinical factors associated with outcome in ovarian and testicular stromal tumors	We will analyze the clinical records to determine which factors influence prognosis	10 years
Secondary	Pathologic and Genetic Correlations	We will correlate the pathologic and genetic data with clinical data to describe factors associated with poor prognosis.	5 years

External Links

•   International OTST Registry official website
•   International PPB/DICER1 Registry