The Correlation Between Ripretinib Exposure and the Efficacy and Safety in Patients with Advanced GISTs

NCT06431451 | Recruiting

• 1 other identifier: 20240102v3.0
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, single-center, observational study to explore the correlation between ripretinib exposure and the efficacy and safety in patients with advanced gastrointestinal stromal tumors

Conditions

Gastrointestinal Stromal Tumors

Keywords

Ripretinib; plasma drug concentration

Outcome Measures

Primary Outcomes (4)

• Plasma Concentration of ripretinib

  The concentration of ripretinib in the plasma was measured.

  Before Dosing and at 0.5, 1, 2, 4, 6, 8,12 and 24 Hours after Dosing

• Plasma Concentration of DP-5439

  The concentration of DP-5439 in the plasma was measured.

  Before Dosing and at 0.5, 1, 2, 4, 6, 8,12 and 24 Hours after Dosing

• Objective Response Rate

  To evaluate objective response rate (ORR,CR+PR) determined by radiology assessment per mRECIST(Response Evaluation Criteriain Solid Tumours), version 1.1 in patients with Metastatic or Unresectable Gastrointestinal Stromal Tumors.Complete response is the disappearance of all lesions with lymph nodes measuring \< 10 mm and normal tumour markers.A decrease in the sum of target disease of ≥ 30% represents partial response.

  2 years

• Disease control rate

  To evaluate disease control rate (CBR,CR+PR+\>16 weeks continuation SD) determined by radiology assessment per mRECIST, version 1.1 in patients with Metastatic or Unresectable Gastrointestinal Stromal Tumors.Complete response is the disappearance of all lesions with lymph nodes measuring \< 10 mm and normal tumour markers.A decrease in the sum of target disease of ≥ 30% represents partial response.Stable disease lies between partial response and progressive disease.

  2 years

Secondary Outcomes (2)

• Progression-free survival

  2 years

• overall survival

  2 years

Eligibility Criteria

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

Study Population

Gastrointestinal stromal tumor patients who are receiving treatment with Ripretinib at the research center.

You may qualify if:

• Patients who are aged ≥ 18 years.
• Gastrointestinal stromal tumors confirmed by histopathological examination, and CD117 and/or DOG-1-positive by immunohistochemistry.
• patients who are currently receiving Ripretinib treatment.
• Subjects must have at least one measurable lesion based on mRECIST v1.1 criteria, and have undergone at least one radiographic evaluation for efficacy analysis.
• Patients with an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 4
• Patient informed consent and signed written consent form.
• The patient was compliant and voluntarily scheduled for follow-up, treatment, laboratory tests, and other study procedures.

You may not qualify if:

• Unable to complete at least 15 consecutive days of Ripretinib due to intolerance or disease progression.
• Individuals with other serious acute or chronic physical or mental health problems, or abnormal laboratory test results that increase the risk associated with participation in the study or use of the drug, or that could interfere with the interpretation of study results, and who, in the opinion of the investigator, are not suitable for participation in the study.

Sponsors & Collaborators

• First Affiliated Hospital, Sun Yat-Sen University: lead

Study Sites (1)

The First Affiliated Hospital, Sun Yat-sen University

Guangzhou, 510080, China

RECRUITING

Related Publications (15)

• von Mehren M, Joensuu H. Gastrointestinal Stromal Tumors. J Clin Oncol. 2018 Jan 10;36(2):136-143. doi: 10.1200/JCO.2017.74.9705. Epub 2017 Dec 8.

  PMID: 29220298 BACKGROUND

• Di Vito A, Ravegnini G, Gorini F, Aasen T, Serrano C, Benuzzi E, Coschina E, Monesmith S, Morroni F, Angelini S, Hrelia P. The multifaceted landscape behind imatinib resistance in gastrointestinal stromal tumors (GISTs): A lesson from ripretinib. Pharmacol Ther. 2023 Aug;248:108475. doi: 10.1016/j.pharmthera.2023.108475. Epub 2023 Jun 10.

  PMID: 37302758 BACKGROUND

• Zalcberg JR. Ripretinib for the treatment of advanced gastrointestinal stromal tumor. Therap Adv Gastroenterol. 2021 Apr 15;14:17562848211008177. doi: 10.1177/17562848211008177. eCollection 2021.

  PMID: 33948116 BACKGROUND

• Janku F, Abdul Razak AR, Chi P, Heinrich MC, von Mehren M, Jones RL, Ganjoo K, Trent J, Gelderblom H, Somaiah N, Hu S, Rosen O, Su Y, Ruiz-Soto R, Gordon M, George S. Switch Control Inhibition of KIT and PDGFRA in Patients With Advanced Gastrointestinal Stromal Tumor: A Phase I Study of Ripretinib. J Clin Oncol. 2020 Oct 1;38(28):3294-3303. doi: 10.1200/JCO.20.00522. Epub 2020 Aug 17.

  PMID: 32804590 BACKGROUND

• Smith BD, Kaufman MD, Lu WP, Gupta A, Leary CB, Wise SC, Rutkoski TJ, Ahn YM, Al-Ani G, Bulfer SL, Caldwell TM, Chun L, Ensinger CL, Hood MM, McKinley A, Patt WC, Ruiz-Soto R, Su Y, Telikepalli H, Town A, Turner BA, Vogeti L, Vogeti S, Yates K, Janku F, Abdul Razak AR, Rosen O, Heinrich MC, Flynn DL. Ripretinib (DCC-2618) Is a Switch Control Kinase Inhibitor of a Broad Spectrum of Oncogenic and Drug-Resistant KIT and PDGFRA Variants. Cancer Cell. 2019 May 13;35(5):738-751.e9. doi: 10.1016/j.ccell.2019.04.006.

  PMID: 31085175 BACKGROUND

• Klug LR, Khosroyani HM, Kent JD, Heinrich MC. New treatment strategies for advanced-stage gastrointestinal stromal tumours. Nat Rev Clin Oncol. 2022 May;19(5):328-341. doi: 10.1038/s41571-022-00606-4. Epub 2022 Feb 25.

  PMID: 35217782 BACKGROUND

• Blay JY, Serrano C, Heinrich MC, Zalcberg J, Bauer S, Gelderblom H, Schoffski P, Jones RL, Attia S, D'Amato G, Chi P, Reichardt P, Meade J, Shi K, Ruiz-Soto R, George S, von Mehren M. Ripretinib in patients with advanced gastrointestinal stromal tumours (INVICTUS): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2020 Jul;21(7):923-934. doi: 10.1016/S1470-2045(20)30168-6. Epub 2020 Jun 5.

  PMID: 32511981 BACKGROUND

• Bauer S, Jones RL, Blay JY, Gelderblom H, George S, Schoffski P, von Mehren M, Zalcberg JR, Kang YK, Razak AA, Trent J, Attia S, Le Cesne A, Su Y, Meade J, Wang T, Sherman ML, Ruiz-Soto R, Heinrich MC. Ripretinib Versus Sunitinib in Patients With Advanced Gastrointestinal Stromal Tumor After Treatment With Imatinib (INTRIGUE): A Randomized, Open-Label, Phase III Trial. J Clin Oncol. 2022 Dec 1;40(34):3918-3928. doi: 10.1200/JCO.22.00294. Epub 2022 Aug 10.

  PMID: 35947817 BACKGROUND

• Li J, Cai S, Zhou Y, Zhang J, Zhou Y, Cao H, Wu X, Deng Y, Huang Z, Dong J, Shen L. Efficacy and Safety of Ripretinib in Chinese Patients with Advanced Gastrointestinal Stromal Tumors as a Fourth- or Later-Line Therapy: A Multicenter, Single-Arm, Open-Label Phase II Study. Clin Cancer Res. 2022 Aug 15;28(16):3425-3432. doi: 10.1158/1078-0432.CCR-22-0196.

  PMID: 35686969 BACKGROUND

• George S, Chi P, Heinrich MC, von Mehren M, Jones RL, Ganjoo K, Trent J, Gelderblom H, Razak AA, Gordon MS, Somaiah N, Jennings J, Meade J, Shi K, Su Y, Ruiz-Soto R, Janku F. Ripretinib intrapatient dose escalation after disease progression provides clinically meaningful outcomes in advanced gastrointestinal stromal tumour. Eur J Cancer. 2021 Sep;155:236-244. doi: 10.1016/j.ejca.2021.07.010. Epub 2021 Aug 12.

  PMID: 34391056 BACKGROUND

• Zalcberg JR, Heinrich MC, George S, Bauer S, Schoffski P, Serrano C, Gelderblom H, Jones RL, Attia S, D'Amato G, Chi P, Reichardt P, Somaiah N, Meade J, Reichert V, Shi K, Sherman ML, Ruiz-Soto R, von Mehren M, Blay JY. Clinical Benefit of Ripretinib Dose Escalation After Disease Progression in Advanced Gastrointestinal Stromal Tumor: An Analysis of the INVICTUS Study. Oncologist. 2021 Nov;26(11):e2053-e2060. doi: 10.1002/onco.13917. Epub 2021 Aug 16.

  PMID: 34313371 BACKGROUND

• Pan C, Cheng Y, He Q, Li M, Bu F, Zhu X, Li X, Xiang X. Evaluating the impact of co-administered drug and disease on ripretinib exposure: A physiologically-based pharmacokinetic modeling approach. Chem Biol Interact. 2023 Mar 1;373:110400. doi: 10.1016/j.cbi.2023.110400. Epub 2023 Feb 9.

  PMID: 36773833 BACKGROUND

• Li X, Shelton MJ, Wang J, Meade J, Ruiz-Soto R. Effects of CYP3A Inhibition, CYP3A Induction, and Gastric Acid Reduction on the Pharmacokinetics of Ripretinib, a Switch Control KIT Tyrosine Kinase Inhibitor. Clin Pharmacol Drug Dev. 2022 Oct;11(10):1165-1176. doi: 10.1002/cpdd.1110. Epub 2022 May 13.

  PMID: 35560823 BACKGROUND

• Demetri GD, Wang Y, Wehrle E, Racine A, Nikolova Z, Blanke CD, Joensuu H, von Mehren M. Imatinib plasma levels are correlated with clinical benefit in patients with unresectable/metastatic gastrointestinal stromal tumors. J Clin Oncol. 2009 Jul 1;27(19):3141-7. doi: 10.1200/JCO.2008.20.4818. Epub 2009 May 18.

  PMID: 19451435 BACKGROUND

• Yang W, Qian H, Yang L, Wang P, Qian H, Chu B, Liu Z, Sun J, Wu D, Sun L, Zhou W, Hu J, Chen X, Shou C, Ruan L, Zhang Y, Yu J. Efficacy and safety of ripretinib in Chinese patients with advanced gastrointestinal stromal tumors: a real-world, multicenter, observational study. Front Oncol. 2023 May 18;13:1180795. doi: 10.3389/fonc.2023.1180795. eCollection 2023.

  PMID: 37274264 BACKGROUND

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

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

Central Study Contacts

xinhua zhang, MD

CONTACT

+8613828463644; zhangxinhua@mail.sysu.edu.cn

yanzhe xia, MD

CONTACT

+8618680238481; xiayzh@mail.sysu.edu.cn

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief physician

Study Record Dates

• First Submitted: December 24, 2023
• First Posted: May 28, 2024
• Study Start: June 1, 2024
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: February 26, 2025

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)