Evaluate the Efficacy and Safety of Radiotherapy Combined With Ripretinib in the Treatment of Unresectable Advanced GIST

Official title

A Multicenter, Single-arm, Prospective Study to Evaluate the Efficacy and Safety of Radiotherapy Combined With Ripretinib in the Treatment of Unresectable Advanced GIST

Overview

The goal of this prospective study is to learn whether there is a synergistic effect when radiotherapy is combined with ripretinib in the treatment of patients with unresectable advanced GIST. It will also learn about the safety of this regimen.The main questions it aim to answer is: Dose radiotherapy combined with ripretinib prolong the time to disease progression for patients with advanced GIST?

Detailed description

ripretinib is the standard fourth-line treatment agent for inoperable advanced GIST patients, but the mPFS is only 6.3 months. Prolonging the time to TKI resistance by using a new treatment approach is important to increase the chances of surgery ,improve the survival time, and quality of life for patients. GIST was previously thought to be a tumor that was insensitive to radiotherapy, but a growing number of studies have shown that GIST is moderately sensitive to radiotherapy and that radiotherapy is effective in controlling the tumor. In our previous work, palliative radiotherapy was given to patients with advanced GIST after multiline drug resistance, and we achieved local control for nearly 2 years while significantly improving the patient's symptoms .

In recent years, radiotherapy technology has been continuously improved, and new radiotherapy techniques can be more precise and have less impact on surrounding organs, making it possible to increase the dose of radiotherapy. For large GIST, our research team has optimized the radiotherapy technique by using simultaneous integrated boost intensity-modulated radiotherapy technique, which can deliver a safe dose at the edge of the tumor while delivering a high dose of radiotherapy at the center of the tumor, ensuring safety and resulting in better therapeutic effects.

We proposed to select some patients with unresectable advanced GIST to explore the feasibility of radiotherapy combined with TKI for the treatment of advanced GIST after failure of first-, second-, and third-line drug therapies with simultaneous addition of radiotherapy to oral ripretinib treatment

Interventions

• Radiation simultaneous integrated boost intensity-modulated radiation therapy combined with ripretinib
  A cumulative radiation dose of 50 to 70 Gy is administered in 25-30 fractions, 5 fractions per week, to the target lesion(s). ripretinib: oral 150mg QD

Primary outcome measures

• Time to disease progression of irradiated lesions [Time frame: Approximately 12 months since the first subject enrolled]

Secondary outcome measures (3)

• Time to disease progression of any lesions [Time frame: Approximately 12 months since the first subject enrolled]
• Overall survival (OS) [Time frame: Approximately 12 months since the first subject enrolled]
• Objective Response Rate(ORR) of irradiated lesions [Time frame: Approximately 12 months since the first subject enrolled]

Eligibility criteria

Inclusion criteria

• Voluntary participation and signed informed consent;
• age: 18 to 75 years, Male or female
• Patients with histologically confirmed GIST and Imaging evaluated as unresectable recurrent and metastatic disease or locally advanced.
• ECOG Performance Score: 0-2
• Subjects who have progressed or documented intolerance after previous first-line, second-line, and third-line treatments.
• At least one measurable lesion in the abdominal or pelvic cavity that has progressed after frontline treatment
• Adequate organ function and bone marrow reserve

Exclusion criteria

• estimated life-expectancy less than 3 months.
• Patients who have received previous radiotherapy to the proposed radiotherapy site, or the tumor has significant mobility, poor tolerance of radiotherapy in adjacent organs, and who are considered unsuitable for radiotherapy after MDT discussion
• Any other clinically significant comorbidities, 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.
• If female, the patient is pregnant or lactating, or plans to become pregnant during the study treatment period

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The First Affiliated Hospital of Chongqing Medical University — Chongqing

Publications

• Hayashi Y, Nguyen VTT. A narrative review of imatinib-resistant gastrointestinal stromal tumors. Gastrointest Stromal Tumor. 2021 Oct;4:6. doi: 10.21037/gist-21-10. Epub 2021 Oct 30. PMID 35814621
• 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- PMID 32511981
• Joensuu H, Eriksson M, Collan J, Balk MH, Leyvraz S, Montemurro M. Radiotherapy for GIST progressing during or after tyrosine kinase inhibitor therapy: A prospective study. Radiother Oncol. 2015 Aug;116(2):233-8. doi: 10.1016/j.radonc.2015.07.025. Epub 2015 Jul 27. PMID 26228971
• Gatto L, Nannini M, Saponara M, Di Scioscio V, Beltramo G, Frezza GP, Ercolani G, Pinna AD, Astolfi A, Urbini M, Brandi G, Biasco G, Pantaleo MA. Radiotherapy in the management of gist: state of the art and new potential scenarios. Clin Sarcoma Res. 2017 Jan 10;7:1. doi: 10.1186/s13569-016-0065-z. eCollection 2017. PMID 28078078
• Li L, Yi X, Cui H, Zhao X, Dang J, Jiang Q, Li Y. Simultaneous Integrated Boost Intensity-Modulated Radiotherapy for Locally Advanced Drug-Resistant Gastrointestinal Stromal Tumors: A Feasibility Study. Front Oncol. 2020 Nov 23;10:545892. doi: 10.3389/fonc.2020.545892. eCollection 2020. PMID 33330024
• Cui H, Li Y, Huang W, Lu W, Yi X. Escalation of radiotherapy dose in large locally advanced drug-resistant gastrointestinal stromal tumors by multi-shell simultaneous integrated boost intensity-modulated technique: a feasibility study. Radiat Oncol. 2022 Dec 28;17(1):216. doi: 10.1186/s13014-022-02179-z. PMID 36578008
• Boruban C, Sencan O, Akmansu M, Atik ET, Ozbek S. Metastatic gastrointestinal stromal tumor with long-term response after treatment with concomitant radiotherapy and imatinib mesylate. Anticancer Drugs. 2007 Sep;18(8):969-72. doi: 10.1097/CAD.0b013e3280e94982. PMID 17667604

Identifiers

NCT: NCT06507683 · 1.0 /2024.05.01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗