Ripretinib Combined With Surgery in Advanced GIST That Have Failed Imatinib Therapy: A Multicenter,Observational Study

Gastrointestinal Stromal Tumor(GIST) Clinical Trial

Official title:

Ripretinib Combined With Surgery in Advanced Gastrointestinal Stromal Tumors That Have Failed Imatinib Therapy: A Multicenter,Observational Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05354388
• Other study ID #: 20211013
• Status: Recruiting
• Start date: October 1, 2021
• Est. completion date: December 30, 2023

Study information

• Verified date: April 2022
• Source: Sichuan Provincial People's Hospital
• Contact: Minghui Pang, Professor
• Phone: 18981838525
• Email: pangmh2000[@]163.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The objective of this observational study is to explore the efficacy and safety of ripretinib treatment combined with surgery in advanced gastrointestinal stromal tumors(GIST) after failure of imatinib therapy.

Description:

This study is a single-arm, multicenter, observational study. A total of approximately 30 subjects were be enrolled. The patient was orally administered with ripretinib150 mg QD. 4 weeks for one cycle. Efficacy was assessed every two cycles. For subjects with PR or SD after ripretinib treatment, resection of gastrointestinal stromal tumor was performed after discussion by MDT and ensure R0 resection as much as possible.Ripretinib 150mg QD was continued 2 weeks after surgery. Thereafter, subjectss entered the follow-up period for at least 1 year. Safety and survival information will be collected

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 30, 2023
• Est. primary completion date: December 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Patients voluntarily, and signed a written informed consent, good compliance with follow-up;

2. 18 years = age < 75 years, male or female;

3. Histopathological examination confirmed the diagnosis of recurrent and/or metastatic advanced unresectable gastrointestinal stromal tumor;

4. According to the modified RECISTv1.1-GIST-specific criteria, the subject has at least one measurable lesion;

5. Subjects must have progressed on imatinib or have documented intolerance to imatinib.

6. ECOG PS of = 2, ASA score = 3 at screening;

7. No other malignant tumors occurred within five years;

Exclusion Criteria:

1. Molecular pathology report PDGFRA Exon 18 mutation(including D842v);

2. Patients with other serious complications who cannot tolerate surgery: such as severe cardiopulmonary disease, heart function below clinical class 2, pulmonary infection, moderate to severe COPD, chronic bronchitis, severe diabetes and/or renal insufficiency, severe hepatitis and/or Child-pugh class C or B whose symptoms are significantly difficult to correct, severe malnutrition, etc;

3. Pregnant or lactating women;

4. 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.

5. Subject has known active central nervous system metastases.

6. Occurrence of bleeding, perforation, obstruction and other disease-related complications, requiring emergency surgery;

7. The patient has participated in or is participating in other clinical studies , or is taking other TKI agents;

Related Conditions & MeSH terms

• Gastrointestinal Stromal Tumor(GIST)
• Gastrointestinal Stromal Tumors

Intervention

Procedure:
• Resection surgery of gastrointestinal stromal tumor
oral administration of Ripretinib 150 mg QD. Resection of gastrointestinal stromal tumors was performed in patients who achieved PR or SD

Locations

Country	Name	City	State
China	Sichuan Provincial People's Hospital	Chengdu	Sichuan

Sponsors (1)

Lead Sponsor	Collaborator
Sichuan Provincial People's Hospital

Country where clinical trial is conducted

China, 

References & Publications (13)

Bannon AE, Klug LR, Corless CL, Heinrich MC. Using molecular diagnostic testing to personalize the treatment of patients with gastrointestinal stromal tumors. Expert Rev Mol Diagn. 2017 May;17(5):445-457. doi: 10.1080/14737159.2017.1308826. Epub 2017 Mar 27. Review. — View Citation

Blay JY, Serrano C, Heinrich MC, Zalcberg J, Bauer S, Gelderblom H, Schöffski 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. Erratum in: Lancet Oncol. 2020 Jul;21(7):e341. — View Citation

Bucher P, Villiger P, Egger JF, Buhler LH, Morel P. Management of gastrointestinal stromal tumors: from diagnosis to treatment. Swiss Med Wkly. 2004 Mar 20;134(11-12):145-53. Review. — View Citation

Den Hollander D, Van der Graaf WTA, Desar IME, Le Cesne A. Predictive factors for toxicity and survival of second-line sunitinib in advanced gastrointestinal stromal tumours (GIST). Acta Oncol. 2019 Nov;58(11):1648-1654. doi: 10.1080/0284186X.2019.1637017. Epub 2019 Jul 26. — View Citation

Dhillon S. Ripretinib: First Approval. Drugs. 2020 Jul;80(11):1133-1138. doi: 10.1007/s40265-020-01348-2. Review. Erratum in: Drugs. 2020 Dec;80(18):1999. — View Citation

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. — View Citation

Mantese G. Gastrointestinal stromal tumor: epidemiology, diagnosis, and treatment. Curr Opin Gastroenterol. 2019 Nov;35(6):555-559. doi: 10.1097/MOG.0000000000000584. Review. — View Citation

Martin-Broto J, Moura DS. New drugs in gastrointestinal stromal tumors. Curr Opin Oncol. 2020 Jul;32(4):314-320. doi: 10.1097/CCO.0000000000000642. Review. — View Citation

Reichardt P. The Story of Imatinib in GIST - a Journey through the Development of a Targeted Therapy. Oncol Res Treat. 2018;41(7-8):472-477. doi: 10.1159/000487511. Epub 2018 Jun 13. Review. — View Citation

Rubin BP, Heinrich MC, Corless CL. Gastrointestinal stromal tumour. Lancet. 2007 May 19;369(9574):1731-41. Review. Erratum in: Lancet. 2007 Aug 4;370(9585):388. — View Citation

Sciot R, Debiec-Rychter M, Daugaard S, Fisher C, Collin F, van Glabbeke M, Verweij J, Blay JY, Hogendoorn PC; EORTC Soft Tissue and Bone Sarcoma Group; Italian Sarcoma Group; Australasian Trials Group. Distribution and prognostic value of histopathologic data and immunohistochemical markers in gastrointestinal stromal tumours (GISTs): An analysis of the EORTC phase III trial of treatment of metastatic GISTs with imatinib mesylate. Eur J Cancer. 2008 Sep;44(13):1855-60. doi: 10.1016/j.ejca.2008.06.003. Epub 2008 Jul 22. — View Citation

Serrano C, George S. Recent advances in the treatment of gastrointestinal stromal tumors. Ther Adv Med Oncol. 2014 May;6(3):115-27. doi: 10.1177/1758834014522491. Review. — View Citation

Wozniak A, Rutkowski P, Piskorz A, Ciwoniuk M, Osuch C, Bylina E, Sygut J, Chosia M, Rys J, Urbanczyk K, Kruszewski W, Sowa P, Siedlecki J, Debiec-Rychter M, Limon J; Polish Clinical GIST Registry. Prognostic value of KIT/PDGFRA mutations in gastrointestinal stromal tumours (GIST): Polish Clinical GIST Registry experience. Ann Oncol. 2012 Feb;23(2):353-60. doi: 10.1093/annonc/mdr127. Epub 2011 Apr 28. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1-year Progression free survival rate	PFS Based on radiographic assessment using Choi criteria	12 monthes
Secondary	objective response rate(ORR)	Objective response rate as determined by confirmed CR + confirmed PR by radiologic review	12 monthes
Secondary	R0 resection rate	R0 is the proportion of subjects with no microscopic residual after resection	1 days after surgery
Secondary	2-year overall survival rate	Proportion of subjects with an overall survival time of at least 2 years	24 monthes
Secondary	time to progression (TTP)	The time from the start of treatment to the progression	12 monthes
Secondary	Duration of continuous medication before surgery	Only for subjects undergoing surgery	12 monthes