ctDNA-Guided Sunitinib And Regorafenib Therapy for GIST

NCT05366816 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 20201368
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants Achieving Overall Response

  The overall response rate (ORR) will be defined as the number of evaluable patients whose best overall response to study treatment is complete response (CR) or partial response (PR). ORR will be assessed using Choi criteria by treating physician.

  Up to 12 months

Secondary Outcomes (4)

• Progression-Free Survival (PFS)

  Up to 3 years

• Overall Survival (OS)

  Up to 3 years

• Number of Participants Achieving Clinical Benefit

  Up to 12 months

• Incidence of Treatment-Related Toxicity and Adverse Events

  Up to 13 months

Study Arms (2)

Group A: KIT Exon 13 receiving Sunitinib

EXPERIMENTAL

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.

Drug: Sunitinib; Drug: Regorafenib

Group B: KIT Exon 17 receiving Regorafenib

EXPERIMENTAL

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.

Drug: Sunitinib; Drug: Regorafenib

Interventions

Sunitinib DRUG

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

Also known as: Sutent, SU11248

Group A: KIT Exon 13 receiving Sunitinib; Group B: KIT Exon 17 receiving Regorafenib

Regorafenib DRUG

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

Also known as: Stivarga, Regonix, BAY 73-4506

Group A: KIT Exon 13 receiving Sunitinib; Group B: KIT Exon 17 receiving Regorafenib

Eligibility Criteria

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

You may qualify if:

• Patients who are ≥ 18 years of age.
• Patients who have histologically confirmed metastatic or unresectable GIST. Unresectable GIST must be confirmed to be unresectable by an experienced surgeon.
• 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.
• Patients who have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2.
• Patient, or legal guardian if permitted by local regulatory authorities, who provides informed consent to participate in the study.
• 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.

You may not qualify if:

• Patients who have received prior treatment with sunitinib or regorafenib.
• 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.
• Patients who are known to be KIT wild type.
• 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.
• 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.
• 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.
• Patients who have experienced any hemorrhage or bleeding event NCI CTCAE version 5.0 Grade 3 or higher within 4 weeks before screening.
• 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.
• Patients who have a non-healing wound, ulcer, or bone fracture.
• 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.

Sponsors & Collaborators

• University of Miami: lead

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

RECRUITING

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Interventions

Sunitinib; regorafenib

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Jonathan Trent, MD, PhD

  University of Miami

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Leonela Wright

CONTACT

305-243-0864; lxw612@med.miami.edu

Jonathan Trent, MD, PhD

CONTACT

305-243-2581; JTrent@med.miami.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Clinical

Study Record Dates

• First Submitted: May 5, 2022
• First Posted: May 9, 2022
• Study Start: October 17, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028
• Last Updated: September 9, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)