Natural History and Biospecimen Acquisition for Children and Adults With Rare Solid Tumors

NCT ID: NCT03739827

Last Updated: 2025-09-24

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 10000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-01-28
• Study Completion Date: 2032-03-31

Brief Summary

Background:

Approximately 150 cases of cancer per one million per year are considered rare cancers. While all tumors originate from genetic changes, a small percentage of these tumors are familial. Researchers want to study these changes in biological samples from people with rare tumors in order to learn more about how these tumors develop. The information obtained from this study may lead to improved screening, preventive guidelines, and treatments.

Objective:

To better understand rare cancers and hereditary cancer syndromes.

Eligibility:

People who have a rare tumor, a family history of a rare tumor, a hereditary cancer syndrome, or a mutation that leads to rare tumors.

Design:

Participants will be screened with questions about their medical history and/or that of their family members. They will give a saliva sample.

Participants who have a tumor will have their medical records and tests reviewed. They will answer questions about their wellbeing and needs. They may provide a tumor tissue sample.

Participants may also have:

• Physical exam
• Clinical photography
• Blood, urine, saliva, and stool samples taken
• Consultation with specialists
• A scan that produces a picture of the body. Either one that uses a small amount of radiation, or one that uses a magnetic field.
• Genetic testing/genetic counseling.

Participants will be contacted once a year. They will answer updated questions about their medical and family history.

Participants will be asked to contact the study team if there are changes in their tumors.

Participants may be invited to join focus groups for people with the same diagnosis of rare tumors.

Participants may be invited to participate in other NIH protocols.

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RARE TUMOR LIST:

1. Acinar cell carcinoma of the pancreas

2. Adamantinoma

3. Adenosqaumous carcinoma of the pancreas

4. Adrenocortical carcinoma

5. Alveolar soft part sarcoma

6. Anaplastic Thyroid Cancer

7. Angiosarcoma

8. Atypical Teratoid Rhabdoid Tumor/MRT

9. Carcinoid

10. Carcinoma of Unknown Primary

11. Chondrosarcoma

12. Chondromyxoid fibroma

13. Chordoma

14. Clear cell renal carcinoma

15. Clear Cell Sarcoma

16. Clear cell sarcoma of kidney

17. Conventional chordoma

18. Dedifferentiated chordoma

19. Desmoid

20. Desmoplastic small round cell tumor

21. Epithelioid hemangioendothelioma

22. Esthenioneuroblastoma

23. Ewing Sarcoma

24. Fibrolamellar carcinoma

25. Fusion negative rhabdomyosarcoma

26. Fusion positive renal cell carcinoma

27. Fusion positive rhabdomyosarcoma

28. Gastro-enteropancreatic neuroendocrine tumor

29. Hepatoblastoma

30. Hereditary Diffuse Gastric Cancer

31. Inflammatory myofibroblastic tumor

32. Kaposiform hemangioendothelioma

33. Malignant ectomesenchymal tumor

34. Malignant peripheral nerve sheath tumor

35. Malignant triton tumor

36. Medullary thyroid cancer

37. Mixed acinar adenocarcinoma

38. Mixed acinar neuroendocrine carcinoma

39. Myxoid Liposarcoma

40. Neuroblastoma

41. Neuroendocrine tumors

42. NUT midline carcinoma

43. Osteosarcoma

44. Pancreas ductal adenocarcinoma with squamous features

45. Pancreatic acinar cell carcinoma

46. Papillary renal cell carcinoma

47. Paraganglioma

48. Parosteal Osteosarcoma

49. Periosteal Osteosarcoma

50. Peripheral nerve sheath tumor

51. Peripheral primitive neuroectodermal tumor

52. Pheochromocytoma

53. Pituitary cancer

54. Poorly differentiated chordoma

55. Renal medullary carcinoma

56. Rhabdomyosarcoma

57. Round cell Liposarcoma

58. Schwannoma

59. Sclerosing Epithelioid Fibrosarcoma

60. SDH deficient GIST

61. SMARCB1 deficient tumors

62. SMARCA4 deficient tumors

63. Synovial sarcoma

64. Undifferentiated Sarcoma

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Detailed Description

Background:

Rare tumors are defined as fewer than 150 incident cases per one million per year. Consequently, only 11 tumor types are common in U.S. adults (prostate, breast, lung/bronchus, colon, uterus, bladder, melanoma, rectum, ovary, non-Hodgkin lymphoma, and kidney/renal pelvis neoplasms) and will not be studied in this trial. One-quarter of all adults with tumor have a rare tumor diagnosis.

All pediatric tumors meet this definition of rare affecting < 1% individuals younger than 20 years per year in the US.

Notably, there is a group of solid tumors that occur so infrequently in children and adults that little is known about the natural history of these tumors, their clinical behavior, molecular/genetic characteristics, optimal management, and drug response.

The NCI and the NIH Clinical Center infrastructure are uniquely suited to conduct studies of rare tumors. There is a precedent in the NCI when even non-interventional studies or initiatives were paradigm-changing. The NCI neurofibromatosis type 1 natural history study allowed the development of groundbreaking interventional trials in participants with plexiform neurofibromas. The Pediatric and Wild-Type Gastrointestinal Stromal Tumor (GIST) Clinic, which involves intramural and extramural experts, not only provided the background for discovery of the molecular features of a very rare disease such as succinate dehydrogenase deficient GIST, but also was able identify therapeutic strategies for this group of participants (for example, avoidance of unnecessarily aggressive surgery). Similarly, studies in adults at the CCR have tremendously advanced the understanding of rare solid tumors occurring primarily in adults such as thymoma, renal cell cancer, and endocrine tumors.

Systematic and longitudinal collection and annotation of clinical history, tissue samples, imaging studies, patient reported outcomes, and other pertinent information in participants with these rare tumors and return of results to participants will provide a service to the participants themselves and to the medical community, in line with the NIH mission of to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability .

Objective:

To comprehensively and longitudinally evaluate the natural history of participants with rare solid tumors or tumor predisposition syndromes, estimating and defining their clinical spectrum (e.g. disease course and survival).

Eligibility:

Participants with a diagnosis of a rare solid tumor (fewer than 15 cases in 100,000 people per year).

OR

Relatives of participants with diagnosis of rare solid tumors

OR

Carriers of germline genetic variants that predispose to rare solid tumor and their relatives.

Design:

This will be a long-term study to comprehensively study participants (and their relatives) with select rare tumors.

Initially participants will provide clinical information (medical history, family medical history, imaging studies and reports, surgical pathology reports, genetic test results, patient-reported outcomes) and biospecimens (archival pathology specimen and saliva) for review by and feedback from the study team.

If indicated, participants will be invited to the study site for additional evaluations and consultation, including clinical phenotyping, genotyping, imaging of tumor sites, and patient reported or other appropriate outcomes.

After evaluation, participants will be provided with recommendations about possible treatment options and might be enrolled into disease specific sub-protocols of this trial.

Since long-term follow-up of individuals with rare tumors, their family members at high risk for developing tumors, and carriers of germline genetic variants is a major feature of the study, we intend to maintain active contact with study subjects for as long as possible.

In addition to evaluating individual participants, this protocol will allow bringing groups of participants (approximately 10-20) with specific rare tumors for a rare tumor clinic on the same day to allow for development of a deeper understanding of rare tumors through the conduct of focus groups.

Conditions

Malignant Solid Tumors; Other Neoplasms Solid Tumors; Pediatric Solid Tumor; Refractory Solid Tumors; Solid Tumor

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

1/Cohort 1

Subjects with a diagnosis of rare tumor (fewer than 15 cases in 100,000 people per year)

No interventions assigned to this group

2/Cohort 2

Relatives of subjects with a rare tumor who have a germline genetic variant that predispose to a rare solid tumor or a subject who has a germline genetic variant that predispose to a rare solid tumor

No interventions assigned to this group

3/Cohort 3

Relatives of subjects with a diagnosis of rare tumor that do NOT have known germline genetic variants that predispose to a rare solid tumor.

No interventions assigned to this group

4/ Cohort 4

Parents/guardians of children with a diagnosis of rare tumor participating in focus groups (if not enrolled in Cohorts 1, 2 or 3)

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Cohort 1: Participants with a diagnosis of a rare solid tumor (fewer than 15 cases in 100,000 people per year). There are no age restrictions beyond the neonatal period (4 weeks).

OR

-Cohort 2: Participants without a rare tumor who have a germline genetic variant that predisposes to a rare solid tumor

OR

-Cohort 3: Relatives of participants with diagnosis of rare solid tumors who do NOT have a known germline variant that predisposes to a rare solid tumor

OR

• Cohort 4: Parent/guardian of child participating in a focus group if not already enrolled on the study.
• Ability of subject or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

None

• Minimum Eligible Age: 4 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mary F Wedekind Malone, D.O.

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Locations

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status: RECRUITING

Oregon Health and Science University

Portland, Oregon, United States

Site Status: RECRUITING

Texas Children's Hospital

Houston, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Barbara J Thomas, R.N.

Role: CONTACT

barbara.thomas2@nih.gov

(240) 858-3633

Mary F Wedekind Malone, D.O.

Role: CONTACT

maryfrances.wedekindmalone@nih.gov

(240) 858-3765

Facility Contacts

National Cancer Institute Referral Office

Role: primary

ncimo_referrals@mail.nih.gov

888-624-1937

Takumi Suzuki

Role: primary

suzukit@ohsu.edu

503-494-3621

Gaylon Stevenson

Role: primary

gnsteve1@texaschildrens.org

(713) 798-495_

Related Links

https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2019-C-0016.html

NIH Clinical Center Detailed Web Page

Other Identifiers

19-C-0016

Identifier Type: -

Identifier Source: secondary_id

190016

Identifier Type: -

Identifier Source: org_study_id