Avapritinib in the Treatment of Unresectable or Recurrent Metastatic GIST Non-exon18 Mutations of PDGFRA

NCT05461664 | Recruiting DMC

• 1 other identifier: No.[2022]107
• Study Type: observational
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, multicenter, observational real-world study to explore the Avapritinib therapy in GIST patients who definited Non-exon18 Mutations of PDGFRA.

Conditions

Gastrointestinal Stromal Tumors; Unresectable Solid Tumor; Recurrent Metastatic Malignant Neoplasm

Keywords

Avapritinib; Genetic testing

Outcome Measures

Primary Outcomes (3)

• 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 nodes measuring \< 10 mm and normal tumour markers.A decrease in the sum of target disease of ≥ 30% represents partial response.

  2 years

• Clinical Benefit Rate

  To evaluate clinical benefit 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 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

• Duration Of Response

  To evaluate duration of response (DOR) 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 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.If a lesion reappears after disappearing in a patient with complete response, progressive disease is declared. However, if such a lesion behaves in this manner in a patient with stable disease or partial response, it is the change in sum of target disease that defines the response or progression.

  2 years

Secondary Outcomes (5)

• Progression-free survival

  2 years

• overall survival

  2 years

• Treatment-emergent adverse events

  2 years

• adverse events of special interest

  2 years

• serious adverse events

  2 years

Eligibility Criteria

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

Study Population

Approximately 74 patients with metastatic or unresectable advanced gastrointestinal stromal tumors from tier-3 hospitals who meet the criteria will be enrolled in the study.

You may qualify if:

• Patients who are aged ≥ 18 years.
• Gastrointestinal stromal tumors confirmed by histopathological examination, and CD- and/or DOG-1-positive by immunohistochemistry.
• Presence of mRECIST v1.1-compliant lesions with at least one measurable lesion (non-lymphadenopathy ≥1.0 cm or ≥2-fold scan slice thickness).
• Treatment with Avapritinib.
• Patients with an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2 at screening.
• 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:

• KIT or PDGFRA wild type.
• Failure to complete continuous atorvastatin for at least 15 days due to intolerability or disease progression.
• Other serious acute or chronic physical or mental problems, or laboratory abnormalities, may increase the risk associated with participation in the study or use of drugs, or interfere with the judgment of the study results and, in the judgment of the investigator, are not considered appropriate for participation in the investigator.

Sponsors & Collaborators

• Xinhua Zhang, MD: lead
• Peking University Cancer Hospital & Institute: collaborator
• Fudan University: collaborator
• Peking University People's Hospital: collaborator
• Chinese PLA General Hospital: collaborator
• Xiangya Hospital of Central South University: collaborator
• Peking University Shenzhen Hospital: collaborator
• Nanfang Hospital, Southern Medical University: collaborator
• West China Hospital: collaborator
• Jiangsu Cancer Institute & Hospital: collaborator
• Shanghai Zhongshan Hospital: collaborator
• Sun Yat-sen University: collaborator
• Xijing Hospital: collaborator
• Shengjing Hospital: collaborator
• Shanghai Jiao Tong University School of Medicine: collaborator
• Liaoning Cancer Hospital & Institute: collaborator
• Sixth Affiliated Hospital, Sun Yat-sen University: collaborator
• Fujian Medical University Union Hospital: collaborator
• Cancer Hospital of Guangxi Medical University: collaborator
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: collaborator
• First Affiliated Hospital of Chongqing Medical University: collaborator
• Chongqing University Cancer Hospital: collaborator

Study Sites (1)

The First Affiliated Hospital, Sun Yat-sen University

Guangzhou, 510080, China

RECRUITING

Related Publications (13)

• Fletcher CD, Berman JJ, Corless C, Gorstein F, Lasota J, Longley BJ, Miettinen M, O'Leary TJ, Remotti H, Rubin BP, Shmookler B, Sobin LH, Weiss SW. Diagnosis of gastrointestinal stromal tumors: A consensus approach. Hum Pathol. 2002 May;33(5):459-65. doi: 10.1053/hupa.2002.123545.

  PMID: 12094370 BACKGROUND

• 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

• 中国临床肿瘤学会胃肠间质瘤专家委员会. 中国胃肠间质瘤诊断治疗共识（2017 年版）. 肿瘤综合治疗电子杂志. 2018;4(1): 31-42.

  BACKGROUND

• Ducimetiere F, Lurkin A, Ranchere-Vince D, Decouvelaere AV, Peoc'h M, Istier L, Chalabreysse P, Muller C, Alberti L, Bringuier PP, Scoazec JY, Schott AM, Bergeron C, Cellier D, Blay JY, Ray-Coquard I. Incidence of sarcoma histotypes and molecular subtypes in a prospective epidemiological study with central pathology review and molecular testing. PLoS One. 2011;6(8):e20294. doi: 10.1371/journal.pone.0020294. Epub 2011 Aug 3.

  PMID: 21826194 BACKGROUND

• Heinrich MC, Corless CL, Demetri GD, Blanke CD, von Mehren M, Joensuu H, McGreevey LS, Chen CJ, Van den Abbeele AD, Druker BJ, Kiese B, Eisenberg B, Roberts PJ, Singer S, Fletcher CD, Silberman S, Dimitrijevic S, Fletcher JA. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol. 2003 Dec 1;21(23):4342-9. doi: 10.1200/JCO.2003.04.190.

  PMID: 14645423 BACKGROUND

• Scheijen B, Griffin JD. Tyrosine kinase oncogenes in normal hematopoiesis and hematological disease. Oncogene. 2002 May 13;21(21):3314-33. doi: 10.1038/sj.onc.1205317.

  PMID: 12032772 BACKGROUND

• Debiec-Rychter M, Sciot R, Le Cesne A, Schlemmer M, Hohenberger P, van Oosterom AT, Blay JY, Leyvraz S, Stul M, Casali PG, Zalcberg J, Verweij J, Van Glabbeke M, Hagemeijer A, Judson I; EORTC Soft Tissue and Bone Sarcoma Group; Italian Sarcoma Group; Australasian GastroIntestinal Trials Group. KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. Eur J Cancer. 2006 May;42(8):1093-103. doi: 10.1016/j.ejca.2006.01.030. Epub 2006 Apr 18.

  PMID: 16624552 BACKGROUND

• Evans EK, Gardino AK, Kim JL, Hodous BL, Shutes A, Davis A, Zhu XJ, Schmidt-Kittler O, Wilson D, Wilson K, DiPietro L, Zhang Y, Brooijmans N, LaBranche TP, Wozniak A, Gebreyohannes YK, Schoffski P, Heinrich MC, DeAngelo DJ, Miller S, Wolf B, Kohl N, Guzi T, Lydon N, Boral A, Lengauer C. A precision therapy against cancers driven by KIT/PDGFRA mutations. Sci Transl Med. 2017 Nov 1;9(414):eaao1690. doi: 10.1126/scitranslmed.aao1690.

  PMID: 29093181 BACKGROUND

• Gebreyohannes YK, Wozniak A, Zhai ME, Wellens J, Cornillie J, Vanleeuw U, Evans E, Gardino AK, Lengauer C, Debiec-Rychter M, Sciot R, Schoffski P. Robust Activity of Avapritinib, Potent and Highly Selective Inhibitor of Mutated KIT, in Patient-derived Xenograft Models of Gastrointestinal Stromal Tumors. Clin Cancer Res. 2019 Jan 15;25(2):609-618. doi: 10.1158/1078-0432.CCR-18-1858. Epub 2018 Oct 1.

  PMID: 30274985 BACKGROUND

• Heinrich MC, Jones RL, von Mehren M, Schoffski P, Serrano C, Kang YK, Cassier PA, Mir O, Eskens F, Tap WD, Rutkowski P, Chawla SP, Trent J, Tugnait M, Evans EK, Lauz T, Zhou T, Roche M, Wolf BB, Bauer S, George S. Avapritinib in advanced PDGFRA D842V-mutant gastrointestinal stromal tumour (NAVIGATOR): a multicentre, open-label, phase 1 trial. Lancet Oncol. 2020 Jul;21(7):935-946. doi: 10.1016/S1470-2045(20)30269-2.

  PMID: 32615108 BACKGROUND

• Jones RL, Serrano C, von Mehren M, George S, Heinrich MC, Kang YK, Schoffski P, Cassier PA, Mir O, Chawla SP, Eskens FALM, Rutkowski P, Tap WD, Zhou T, Roche M, Bauer S. Avapritinib in unresectable or metastatic PDGFRA D842V-mutant gastrointestinal stromal tumours: Long-term efficacy and safety data from the NAVIGATOR phase I trial. Eur J Cancer. 2021 Mar;145:132-142. doi: 10.1016/j.ejca.2020.12.008. Epub 2021 Jan 16.

  PMID: 33465704 BACKGROUND

• George S, Jones RL, Bauer S, Kang YK, Schoffski P, Eskens F, Mir O, Cassier PA, Serrano C, Tap WD, Trent J, Rutkowski P, Patel S, Chawla SP, Meiri E, Gordon M, Zhou T, Roche M, Heinrich MC, von Mehren M. Avapritinib in Patients With Advanced Gastrointestinal Stromal Tumors Following at Least Three Prior Lines of Therapy. Oncologist. 2021 Apr;26(4):e639-e649. doi: 10.1002/onco.13674. Epub 2021 Feb 1.

  PMID: 33453089 BACKGROUND

• Grunewald S, Klug LR, Muhlenberg T, Lategahn J, Falkenhorst J, Town A, Ehrt C, Wardelmann E, Hartmann W, Schildhaus HU, Treckmann J, Fletcher JA, Jung S, Czodrowski P, Miller S, Schmidt-Kittler O, Rauh D, Heinrich MC, Bauer S. Resistance to Avapritinib in PDGFRA-Driven GIST Is Caused by Secondary Mutations in the PDGFRA Kinase Domain. Cancer Discov. 2021 Jan;11(1):108-125. doi: 10.1158/2159-8290.CD-20-0487. Epub 2020 Sep 24.

  PMID: 32972961 BACKGROUND

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors; Neoplasm Metastasis

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; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Xinhua Zhang, PhD

  First affiliated hosptial,Sun Yat-sen university

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xinhua Zhang, PhD

CONTACT

+8620-87332200; zhangxinhua@mail.sysu.edu.cn

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: First Affiliated Hospital, Sun Yat-Sen University

Study Record Dates

• First Submitted: July 9, 2022
• First Posted: July 18, 2022
• Study Start: July 10, 2022
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: February 26, 2025

Record last verified: 2025-02

Locations

CN (1)