Clinical trial NCT05354388: Ripretinib Combined With Surgery in Advanced GIST That Have Failed Imatinib Therapy: A Multicenter,Observational Study
Official title: Ripretinib Combined With Surgery in Advanced Gastrointestinal Stromal Tumors That Have Failed Imatinib Therapy: A Multicenter,Observational Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Gastrointestinal Stromal Tumor(GIST)
Lead sponsor: Sichuan Provincial People's Hospital
Sponsor class: OTHER
First posted: 2022-04-29
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The patients enrolled in this study will be outpatients from Sichuan Provincial People's Hospital and cooperative hospitals

Brief 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.

Detailed 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

Eligibility criteria: 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;

Primary outcomes:
measure: 1-year Progression free survival rate
timeFrame: 12 monthes
Secondary outcomes:
measure: objective response rate（ORR）
timeFrame: 12 monthes
measure: R0 resection rate
timeFrame: 1 days after surgery
measure: 2-year overall survival rate
timeFrame: 24 monthes
measure: time to progression (TTP)
timeFrame: 12 monthes
measure: Duration of continuous medication before surgery
timeFrame: 12 monthes
Other outcomes:
Locations:
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
state: Sichuan
Study officials:
affiliation: Sichuan Provincial People's Hospital
name: Minghui Pang, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rubin BP, Heinrich MC, Corless CL. Gastrointestinal stromal tumour. Lancet. 2007 May 19;369(9574):1731-41. doi: 10.1016/S0140-6736(07)60780-6.
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.
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.
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.
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. doi: 10.4414/smw.2004.10530.
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.
citation: Dhillon S. Ripretinib: First Approval. Drugs. 2020 Jul;80(11):1133-1138. doi: 10.1007/s40265-020-01348-2.
citation: Mantese G. Gastrointestinal stromal tumor: epidemiology, diagnosis, and treatment. Curr Opin Gastroenterol. 2019 Nov;35(6):555-559. doi: 10.1097/MOG.0000000000000584.
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.
citation: 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.
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.
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.
citation: 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.