ctDNA-Guided Sunitinib And Regorafenib Therapy for GIST

NCT ID: NCT05366816

Last Updated: 2025-09-09

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-17
• Study Completion Date: 2028-12-31

Brief Summary

The purpose of this research is to test if mutations (changes in DNA) in exons (segment of DNA or RNA containing information that has the instructions for making proteins) in the KIT gene can be used to predict the body's response to standard of care treatment.

Conditions

Gastrointestinal Stromal Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group A: KIT Exon 13 receiving Sunitinib

Participants with KIT mutation on exon 13 will receive Sunitinib. Participants showing disease progression after first-assigned Sunitinib therapy have the option to receive Regorafenib therapy. Total allotted time for treatment is up to 12 months.

Group Type: EXPERIMENTAL

Sunitinib

Intervention Type: DRUG

37.5 mg of Sunitinib orally (PO), once daily on a 28-day treatment cycle.

Regorafenib

Intervention Type: DRUG

120.0 mg of Regorafenib, once daily by mouth 3 weeks on 1 week off on a 4-week treatment cycle.

Group B: KIT Exon 17 receiving Regorafenib

Participants with KIT mutation on exon 17 will receive Regorafenib. Participants showing disease progression after first-assigned Regorafenib therapy have the option to receive Sunitinib therapy. Total allotted time for treatment is up to 12 months.

Group Type: EXPERIMENTAL

Sunitinib

Intervention Type: DRUG

37.5 mg of Sunitinib orally (PO), once daily on a 28-day treatment cycle.

Regorafenib

Intervention Type: DRUG

120.0 mg of Regorafenib, once daily by mouth 3 weeks on 1 week off on a 4-week treatment cycle.

Interventions

Sunitinib

37.5 mg of Sunitinib orally (PO), once daily on a 28-day treatment cycle.

Intervention Type: DRUG

Regorafenib

120.0 mg of Regorafenib, once daily by mouth 3 weeks on 1 week off on a 4-week treatment cycle.

Intervention Type: DRUG

Other Intervention Names

Sutent; SU11248; Stivarga; Regonix; BAY 73-4506

Eligibility Criteria

Inclusion Criteria

1. Patients who are ≥ 18 years of age.

2. Patients who have histologically confirmed metastatic or unresectable GIST. Unresectable GIST must be confirmed to be unresectable by an experienced surgeon.

3. Patients who received imatinib prior treatment regimens, including adjuvant therapy, with objective disease progression, inadequate clinical benefit, or intolerance. Additionally, disease progression or intolerance to other systemic therapies including investigational agents and radiotherapy is allowed. Patients who experienced intolerance to prior therapies must have objective disease progression prior to enrollment.

4. Patients who have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2.

5. Patient, or legal guardian if permitted by local regulatory authorities, who provides informed consent to participate in the study.

6. Presence of proto-oncogene c-KIT (KIT) exon 13 or 17 secondary mutation will be determined through a circulating tumor DNA (ctDNA) blood test or biopsy performed as per standard of care.

Exclusion Criteria

1. Patients who have received prior treatment with sunitinib or regorafenib.

2. Patients who have received more than 2 different prior tyrosine kinase inhibitor (TKI) treatment regimens. If a patient receives the same TKI more than once sequentially (eg, imatinib followed by a period without systemic therapy and retreatment with imatinib), that will be counted as a single TKI treatment regimen.

3. Patients who are known to be KIT wild type.

4. Patients who received any systemic anticancer therapy within 2 weeks before. Prior radiotherapy to major organs within 2 weeks of admission, or focal radiotherapy, such as to bones, limbs, or other areas not involving major organs, within 3 days.

5. Patients who have clinically significant, uncontrolled, cardiovascular disease, including congestive heart failure Grades II, III or IV according to the New York Heart Association classification, myocardial infarction or unstable angina within the previous 6 months, or uncontrolled hypertension.

6. Patients who have experienced arterial thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), or pulmonary embolism within the 6 months before randomization or venous thrombotic events such as deep vein thrombosis within the 3 months before screening.

7. Patients who have experienced any hemorrhage or bleeding event NCI CTCAE version 5.0 Grade 3 or higher within 4 weeks before screening.

8. Patients who have a known risk of intracranial bleeding, such as a brain aneurysm or history of intracranial bleeding within 1 year prior to screening.

9. Patients who have a non-healing wound, ulcer, or bone fracture.

10. Patients who have poor organ function as defined by one or more of the following laboratory parameters:

• Persistent proteinuria of NCI-CTCAE version 4.03 Grade 3 or higher
• Alanine aminotransferase and aspartate aminotransferase (AST) > 3 × upper limit of normal (ULN) if no hepatic metastases are present; > 5 × ULN if hepatic metastases are present.
• Total bilirubin >1.5 × ULN; and in presence of Gilbert's syndrome, total bilirubin > 3 × ULN or direct bilirubin > 1.5 × ULN.
• Estimated (Cockcroft-Gault formula) or measured creatinine clearance < 40 mL/min.
• Platelet count < 90 × 109/L and absolute neutrophil count (ANC) < 1.0 × 10^9/L.
• Hemoglobin < 9 g/dL. Transfusion and erythropoietin may be used to reach at least 9 g/dL, but must have been administered at least 2 weeks before screening.

11. Patients who have received neutrophil growth factor support within 14 days of screening.

12. Patients who require therapy with a concomitant medication that is a strong inhibitor or strong inducer of CYP3A4.

13. Patients who have had a major surgical procedure (minor surgical procedures such as central venous catheter placement, tumor needle biopsy, and feeding tube placement are not considered major surgical procedures) within 14 days of screening. Patient has significant traumatic injury within 28 days before screening.

14. Patients who have a history of another primary malignancy that has been diagnosed or required therapy within 2 years before screening. (The following are exempt from the 2-year limit: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, and completely resected carcinoma in situ of any site.)

15. Patients who have a history of a seizure disorder requiring anti-seizure medication.

16. Patients who have metastases to the brain.

17. Patients who are unwilling or unable to comply with scheduled visits, drug administration plan, laboratory tests, or other study procedures and study restrictions.

18. Patients who have a QT interval corrected using Fridericia's formula (QTcF) of > 450 msec.

19. Women who are unwilling, if not postmenopausal or surgically sterile, to abstain from sexual intercourse or employ highly effective contraception from the time of randomization and for at least 30 days after the last dose of study drug. Men who are unwilling, if not surgically sterile, to abstain from sexual intercourse or employ highly effective contraception from the time of randomization and for at least 90 days after the last dose of study drug. Refer to Appendix G for acceptable methods of contraception.

20. Women who are pregnant, as documented by a serum beta human chorionic gonadotropin (β-hCG) pregnancy test consistent with pregnancy, obtained within 7 days before the treatment assignment. Females with β-hCG values that are within the range for pregnancy but are not pregnant (false positives) may be enrolled with written consent of the investigator, after pregnancy has been ruled out. Females of non-childbearing potential (postmenopausal for more than 1 year; bilateral tubal ligation; bilateral oophorectomy; hysterectomy) do not require a serum β-hCG test.

21. Women who are breastfeeding.

22. Patients who have prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the Investigator's opinion, could affect the safety of the patient; alter the absorption, distribution, metabolism, or excretion of the study drug; or impair the assessment of study results.

23. Patients with impaired decision-making capacity.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Miami

OTHER

Sponsor Role: lead

Responsible Party

Jonathan Trent, MD, PhD

Professor of Clinical

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jonathan Trent, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

University of Miami

Miami, Florida, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Leonela Wright

Role: CONTACT

lxw612@med.miami.edu

305-243-0864

Jonathan Trent, MD, PhD

Role: CONTACT

JTrent@med.miami.edu

305-243-2581

Facility Contacts

Leonela Wright

Role: primary

lxw612@med.miami.edu

305-243-0864

Jonathan Trent, MD, PhD

Role: backup

JTrent@med.miami.edu

305-243-2581

Other Identifiers

20201368

Identifier Type: -

Identifier Source: org_study_id