A Study to Assess DCC-2618 and Sunitinib in Patients With Advanced GIST After Treatment With Imatinib

NCT04633122 | Completed Phase 2 Results FDA Drug

• 1 other identifier: ZL-2307-003
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 18

Brief Summary

the primary objective of this study is to assess the efficacy (progression-free survival,PFS) of DCC-2618 (ripretinib, ZL-2307) and sunitinib in patients with advanced gastrointestinal stromal tumors after treatment with imatinib. This study will enroll approximately 98 subjects in around 18 sites in China mainland, and all subjects will be receiving DCC-2618 or Sunitinib in equal chance as treatment.

Conditions

Gastrointestinal Stromal Tumor(GIST)

Keywords

Gastrointestinal Stromal Tumors,GIST,DCC-2618,Ripretinib

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  PFS is defined as the time interval from randomization to the first occurrence of progressive disease based on assessment of the independent radiology review (IRR) or death due to any causes.

  Approximately 12 months.

Secondary Outcomes (2)

• Objective Response Rate (ORR)

  Approximately 12 months.

• Disease Control Rate (DCR)

  Approximately 12 months.

Study Arms (2)

Ripretinib

EXPERIMENTAL

50mg/tablet,150 mg QD continuous administration, 6 weeks (42 days) for a cycle.

Drug: Ripretinib

Sunitinib

ACTIVE COMPARATOR

12.5mg/capsule, 50 mg QD, in 6 weeks (42 days) with 4 weeks continuous dosing followed by 2 weeks break.

Drug: Sunitinib

Interventions

Ripretinib DRUG

Oral kinase inhibitor

Also known as: DCC-2618

Ripretinib

Sunitinib DRUG

second-line therapy in GIST patients who have progressed after imatinib treatment or are intolerant to imatinib

Sunitinib

Eligibility Criteria

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

You may qualify if:

• Male or female patients ≥18 years of age.
• Histological diagnosis of advanced GIST and capability of providing tumor tissue sample (the interval between tumor tissue collection and signing of informed consent form should be less than 3 years). Otherwise, biopsy is required.
• Provide molecular test report with KIT/PDGFRA mutation status prior to randomization.
• Patients must have progressed on imatinib or have documented intolerance to imatinib. Subjects must have discontinued imatinib treatment 10 days prior to the first dose of the study drug. All prior imatinib treatments will be considered as first-line (such as imatinib adjuvant therapy and imatinib dose increase).
• ECOG PS of 0-2.
• Female patients of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-hCG) pregnancy test at screening.
• Patients of reproductive potential must agree to follow the contraception requirements.
• At least 1 measurable lesion according to the "RECIST v1.1-GIST-specific Criteria" (non-nodal lesions must be ≥1.0 cm in the long axis or ≥ double the slide thickness in the long axis) ; obtaining radiographic image results within 28 days prior to the first dose of study drug.
• Good organ function and bone marrow reserve function, including:
• Neutrophil count ≥ 1,000/µL
• Hemoglobin ≥ 8 g/dL
• Platelet count ≥ 75,000/µL
• Total bilirubin ≤ 1.5 × the upper limit of normal (ULN)
• AST and ALT ≤ 3×ULN, and AST and ALT≤ 5×ULN in the presence of hepatic metastases
• Creatinine clearance ≥ 50 mL/min (based on Cockcroft-Gault estimation Formulas for calculation)

You may not qualify if:

• Treatment with any other line of therapy in addition to imatinib for advanced GIST. Imatinib-containing combination therapy in the first-line treatment should not be enrolled.
• Patients with a prior or concurrent malignancy whose natural history or treatment have the potential to interfere with the safety or efficacy assessment of this clinical trial are not eligible.
• Patient has known active central nervous system metastases.
• New York Heart Association class II - IV heart disease, myocardial infarct, active ischemia or any other uncontrolled cardiac condition within the first 6 months of the first dose of study drug such as angina pectoris, clinically significant cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart failure.
• Left ventricular ejection fraction (LVEF) \< 50%.
• Arterial thrombotic or embolic events such as cerebrovascular accident (including ischemic attacks) or hemoptysis within 6 months before the first dose of study drug.
• Venous thrombotic events (e.g. deep vein thrombosis) or pulmonary arterial events (e.g. pulmonary embolism) within 1 month before the first dose of study drug. Patients on stable anticoagulation therapy for at least one month are eligible.
• lead electrocardiogram (ECG) demonstrating QT interval corrected by Fridericia's formula \> 450 ms in males or \> 470 ms in females at screening or history of long QT interval syndrome.
• Use of strong or moderate inhibitors and/or inducers of cytochrome P450 (CYP) 3A4 within 14 days or 5 x the half-life (whichever is longer) prior to the first dose of study drug, including certain herbal medications (eg, St. John's Wort) and consumption of grapefruit or grapefruit juice within 14 days prior to the first dose of study drug.
• Use of known substrates or inhibitors of breast cancer resistance protein (BCRP) transporters within 14 days or 5 x the half-life (whichever is longer) prior to the first dose of study drug.
• Major surgeries (e.g. abdominal laparotomy) within 4 weeks of the first dose of study drug; all major surgical wounds must be healed and free of infection or dehiscence before the first dose of study drug.
• Any other clinically significant comorbidities, such as uncontrolled pulmonary disease, active infection, or any other condition, which in the judgment of the investigator, could compromise compliance with the protocol, interfere with interpretation of the study results, or predispose the patient to safety risks.
• Known human immunodeficiency virus or hepatitis C infection only if the patient is taking medications that are excluded per protocol, hepatitis B virus (HBV) DNA \> 2000 IU/ml or \> 104 copies/ml.
• Female patients who are pregnant or lactating or who plan to become pregnant during the study treatment period.
• Known hypersensitivity to any component of the study drug. Patients with Stevenson Johnson syndrome in previous TKI treatment need to be excluded.

Sponsors & Collaborators

• Zai Lab (Shanghai) Co., Ltd.: lead

Study Sites (18)

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Location

Chinese PLA General Hospital

Beijing, Beijing Municipality, China

Location

The General Hospital of Peking University

Beijing, Beijing Municipality, China

Location

The First Affiliated Hospital of Chongqing Medical Universty

Chongqing, Chognqing, China

Location

Fujian Medical University Union Hospital

Fuzhou, Fujian, China

Location

The Cancer Hospital of Sun Yat-sen University

Guangzhou, Guangdong, China

Location

The First Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, China

Location

The sixth Affiliated hospital of Sun Yat-sen University

Guangzhou, Guangdong, China

Location

The 4th Hospital of Hebei Medical University

Shijiazhuang, Hebei, China

Location

The Affiliated Hospital of Haerbin MedicalUniversity

Harbin, Heilongjiang, China

Location

Union Hospital of HUST

Wuhan, Hubei, China

Location

The Affiliated Hospital of Qingdao University

Qingdao, Shandong, China

Location

Fudan University Cancer Hospital

Shanghai, Shanghai Municipality, China

Location

Fudan University, Zhongshan Hospital

Shanghai, Shanghai Municipality, China

Location

Renji Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, China

Location

West China Hospital of Sichuan University

Chengdu, Sichuan, China

Location

The Affiliated Hospital of Xinjiang Medical University

Ürümqi, Xinjiang, China

Location

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Location

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Interventions

ripretinib; Sunitinib

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

Results Point of Contact

• Title: Medical Director
• Organization: Zai Lab

Medinfo@zailaboratory.com

+86 4008201022

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2020
• First Posted: November 18, 2020
• Study Start: November 25, 2020
• Primary Completion: July 20, 2022
• Study Completion: July 20, 2022
• Last Updated: February 10, 2025
• Results First Posted: January 15, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (18)