A Phase II Trial of the DNA Methyl Transferase Inhibitor, Guadecitabine (SGI-110), in Children and Adults With Wild Type GIST,Pheochromocytoma and Paraganglioma Associated With Succinate Dehydrogenase Deficiency and HLRCC-associated Kidney Cancer

NCT03165721 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 17008817-C-0088
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Wild-type gastrointestinal stromal tumor (GIST) is a cancer in the esophagus, stomach, or intestines. It does not respond well to standard chemotherapy or radiation therapy. Most people with GIST are treated with imatinib. But it may not work in many children with GIST. Researchers think the drug SGI-110 may help treat people with GIST, pheochromocytoma and paraganglioma (PHEO/PGL), or kidney cancer related to hereditary leiomyomatosis and renal cell carcinoma (HLRCC). Objective: To learn if SGI-110 causes GIST tumors to shrink or slows their growth. Also to test how it acts in the body. Eligibility: People ages 12 and older who have GIST, PHEO/PGL, or HLRCC that has not responded to other treatments Design: Participants will be screened with:

• Physical exam
• Urine tests
• Computed tomography (CT) or magnetic resonance imaging (MRI), or fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan: A machine takes pictures of the body.
• Blood tests Participants will be injected with SGI-110 under the skin each day for 5 days. This cycle will repeat every 28 days. The cycles repeat until their side effects get too bad or their cancer gets worse. Participants will have tests throughout study:
• Physical exam and blood and urine tests before each cycle
• Blood tests on days 1, 7, 14, and 28 of the first cycle.
• Scans before cycle 1 and then every other cycle.
• Questionnaires about their pain and quality of life
• Tumor biopsy for those 18 and older: A needle removes a small piece of tumor. After they stop treatment, participants will have a final visit. This includes an evaluation of their health, pain, and quality of life. ...

Conditions

Paraganglioma; Gastrointestinal Stromal Tumors; Carcinoma, Renal Cell; Renal Neoplasms; Pheochromocytoma

Keywords

Renal Cancer; DNA Hypermethylation; Gastrointestinal Stromal Tumors; DNA Methyltransferase (DNMT) Inhibitor; Succinate Dehydrogenase (SDH) Deficiency

Outcome Measures

Primary Outcomes (1)

• Number of Participants With an Overall Response (Complete Response or Partial Response) of SGI-11 Using the Response Evaluation Criteria in Solid Tumors (RECIST)

  Clinical activity of SGI-11 was assessed using the RECISTv1.1. Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.

  After the first 4 weeks, then every 8 weeks up to 65 weeks

Secondary Outcomes (1)

• Change in Distress From Baseline

  Baseline, end of cycle 4, and post therapy follow up, approximately 30 days after the final dose of study drug

Study Arms (3)

Patients ≥ 12 Years of Age w/Wild-Type GIST

EXPERIMENTAL

SGI-110 administered subcutaneously at 45mg/m\^2/day x 5 days on a 28-day cycle Gastrointestinal stromal tumor (GIST)

Drug: SGI-110 (guadecitabine)

Patients ≥ 12 Years of Age w/PHEO/PGL with SDH-deficient PHE

EXPERIMENTAL

SGI-110 administered subcutaneously at 45mg/m\^2/day x 5 days on a 28-day cycle Pheochromocytoma and Paraganglioma (PHEO/PGL) with succinate dehydrogenase (SDH)-deficient PHE

Drug: SGI-110 (guadecitabine)

Patients ≥ 12 Years of Age w/HLRCC-associated Renal Cell Ca

EXPERIMENTAL

SGI-110 administered subcutaneously at 45mg/m\^2/day x 5 days on a 28-day cycle Hereditary leiomyomatosis and renal cell carcinoma (HLRCC)-associated Renal Cell Ca

Drug: SGI-110 (guadecitabine)

Interventions

SGI-110 (guadecitabine) DRUG

SGI-110 will be administered subcutaneously at 45mg/m\^2/day x 5 days on a 28-day cycle. Cycles may be repeated until there is evidence of tumor progression clinically or by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or there is intolerable toxicity that is not alleviated by dose reduction.

Also known as: guadecitabine

Patients ≥ 12 Years of Age w/HLRCC-associated Renal Cell Ca; Patients ≥ 12 Years of Age w/PHEO/PGL with SDH-deficient PHE; Patients ≥ 12 Years of Age w/Wild-Type GIST

Eligibility Criteria

• Age: 12 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must:
• Have recurrent or refractory/unresectable disease for which there is no known curative therapy.
• Wild type-gastrointestinal stromal tumors (GIST): Patients with recurrent or progressive disease will be eligible. Newly diagnosed patients with resectable localized disease will not be eligible. Newly diagnosed patients with metastatic disease and newly diagnosed patients with residual tumor following surgical debulking will be eligible.
• Paraganglioma-Pheochromocytoma (PHEO/PGL): Patients with recurrent or progressive disease will be eligible. Newly diagnosed patients with PHEO/PGL that is metastatic at diagnosis and/or unresectable will be eligible Patients with PHEO/PGL with localized (non-metastatic), resectable disease will not be eligible.
• Renal cell cancer associated with HLRCC: Patients with localized, resectable HLRCC-associated renal cell cancer will not be eligible. Patients with metastatic and/or unresectable Hereditary leiomyomatosis and renal cell cancer (HLRCC)-associated renal cell cancer will be eligible.
• Have one of the following confirmed histologically, cytologically, or through biochemical testing:
• wild-type GIST (GIST without KIT or platelet derived growth factor receptor alpha (PDGFRA) mutation);
• PHEO/PGL with a germline mutation in Succinate Dehydrogenase Complex Flavoprotein Subunit A (SDHA), Succinate Dehydrogenase Complex Flavoprotein Subunit B (SDHB), SDHC, or SDHD;
• renal cell cancer associated with HLRCC.
• Testing will be performed in Clinical Laboratory Improvement Amendments (CLIA) certified labs using genetic tests for KIT/PDGFRA and testing panels developed for patients with PHEO/PGL. Results from outside labs will be accepted. Pathologic diagnosis will be reviewed and verified at the Clinical Center.
• Age: be greater than or equal to 12 years of age
• Because there is no dosing or adverse event data currently available on the use of SGI-110 in children \< 18 year of age, children \< 12 years of age will be excluded from this study, but may be eligible for future pediatric trials should the results of the study be positive.
• \- Measurable disease:
• Have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as greater than or equal to 20 mm with conventional techniques or as greater than 10 mm with spiral computed tomography (CT) scan.
• Prior Therapy

You may not qualify if:

• Patients with any one the following will be excluded:
• Ongoing radiation therapy, chemotherapy, hormonal therapy directed at the tumor, immunotherapy, or biologic therapy, including investigational agents for their disease.
• History of allergic reactions to SGI-110 or decitabine.
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, symptomatic pulmonary disease or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant or breastfeeding
• Pregnant women are excluded from this study because SGI-110 is a derivative of decitabine which has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with SGI-110, breastfeeding should be discontinued if the mother is treated with SGI-110.
• These potential risks may also apply to other agents used in this study.
• Any evidence of severe or uncontrolled systemic disease, active infection, active bleeding diatheses, or renal transplant, including any patient known to have hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) will be excluded. Patients with HIV who have adequate cluster of differentiation 4 (CD4) count, not requiring antiretroviral medication, may be enrolled.
• Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Ligon JA, Sundby RT, Wedekind MF, Arnaldez FI, Del Rivero J, Wiener L, Srinivasan R, Spencer M, Carbonell A, Lei H, Shern J, Steinberg SM, Figg WD, Peer CJ, Zimmerman S, Moraly J, Xu X, Fox S, Chan K, Barbato MI, Andresson T, Taylor N, Pacak K, Killian JK, Dombi E, Linehan WM, Miettinen M, Piekarz R, Helman LJ, Meltzer P, Widemann B, Glod J. A Phase II Trial of Guadecitabine in Children and Adults with SDH-Deficient GIST, Pheochromocytoma, Paraganglioma, and HLRCC-Associated Renal Cell Carcinoma. Clin Cancer Res. 2023 Jan 17;29(2):341-348. doi: 10.1158/1078-0432.CCR-22-2168.

  PMID: 36302175 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Paraganglioma; Gastrointestinal Stromal Tumors; Carcinoma, Renal Cell; Kidney Neoplasms; Pheochromocytoma

Interventions

guadecitabine

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Dr. John Glod
• Organization: National Cancer Institute

john.glod@nih.gov

240-760-6194

Study Officials

• John W Glod, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 23, 2017
• First Posted: May 24, 2017
• Study Start: August 16, 2017
• Primary Completion: February 24, 2020
• Study Completion: February 24, 2020
• Last Updated: February 18, 2026
• Results First Posted: May 10, 2021

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)