Atezolizumab and BEvacizumab With STereotactic Body Radiotherapy for Advanced Hepatocellular Carcinoma

Официальное название

Atezolizumab and Bevacizumab With Stereotactic Body Radiotherapy for Advanced Hepatocellular Carcinoma

Обзор

To determine the efficacy and safety of atezolizumab-bevacizumab combination therapy plus stereotactic body radiotherapy(SBRT) in patients with advanced hepatocellular carcinoma, Subjects will start SBRT for one or more primary cancers and/or metastatic lesions and no more than 5 sites within two month before and after the start date of atezolizumab-bevacizumab combination therapy. In this study, it is expected to improve the treatment response rate of atezolizumab-bevacizumab therapy, which is currently first-line chemotherapy but has a low treatment response rate.

Подробное описание

The subjects with advanced hepatocellular carcinoma who are indicated for the first-line atezolizumab-bevacizumab combination therapy are the primary subjects, and if they voluntarily agree to the clinical trial after explanation of the clinical trial, they are included in the clinical trial. Subjects should begin SBRT(stereotactic body radiotherapy) to one or more but not more than five sites for primary cancer and/or metastatic lesions within two month before and after the start date of atezolizumab-bevacizumab combination therapy.

The followings are evaluation items for each visit.

Visit 1 (-6\~0 weeks) ± 7days \*Screening

* Informed consent form * Inclusion Criteria/ Exclusion Criteria * Medical history and physical examination * Staging via CT, MRI, PET-CT, etc. (PET-CT examination is not compulsory) * CBC, SMA, PT/aPTT, Tumor markers, Biomarkers * Stool microbiota NGS * QoL Questionnaire(EORTC-QLQ-C30 V3)

Visit 2 (0\~7 weeks) ± 7 days \*During SBRT

* Confirmation of adverse events * QoL Questionnaire(EORTC-QLQ-C30 V3)

Visit 3 (1\~8 weeks) \*1 week after SBRT

* Confirmation of adverse events * CBC, SMA, PT/aPTT, Tumor markers, Biomarkers * QoL Questionnaire(EORTC-QLQ-C30 V3)

Visit 4 (6\~9 weeks) ± 7 days \*After 2 cycles of chemotherapy

* Confirmation of adverse events * CBC, SMA, PT/aPTT, Tumor markers, Biomarkers * Stool microbiota NGS * QoL Questionnaire(EORTC-QLQ-C30 V3)

Visit: 5\~12 (3\~36 months) ± 2 weeks \*Follow-up

* Confirmation of adverse events * Evaluation of effectiveness\* (Imaging tests, Tumor markers, CBC, SMA, PT/aPTT are performed according to the need) * QoL Questionnaire(EORTC-QLQ-C30 V3)

Вмешательства

• Лучевая терапия Stereotactic body radiotherapy
  Patients with advanced hepatocellular carcinoma who are indicated for the first-line atezolizumab-bevacizumab combination therapy are the primary subjects, and they should begin stereotactic radiotherapy to one or more but not more than five sites for primary cancer and/or metastatic lesions within two month before and after the start date of atezolizumab-bevacizumab combination therapy.

Первичные конечные точки

• Progression-free survival at 6 month [Срок оценки: 6 months after registration]

Вторичные конечные точки (4)

• Overall survival [Срок оценки: 36 months after registration]
• Objective response rate [Срок оценки: 36 months after registration]
• Adverse event (Toxicity) [Срок оценки: 36 months after registration]
• Tumor marker response: AFP, PIVKA-II [Срок оценки: 36 months after registration]

Критерии участия

Критерии включения

• Age 19 to 80 years old
• Liver function Child-Pugh class A
• ECOG 0-1
• Patient clinically or pathologically diagnosed with hepatocellular carcinoma
• Advanced hepatocellular carcinoma that is inoperable
• Satisfies the dose limits for normal organs and lesions of an appropriate size to be included in the scope of radiotherapy.

Критерии исключения

• Brain metastases
• Have a history of malignancy other than hepatocellular carcinoma within the last 5 years (except for malignancies with little risk of metastasis or death, e.g., adequately treated cervical carcinoma in situ, non-melanoma skin cancer, localized prostate cancer, tubular carcinoma in situ, or stage 1 uterine cancer.)
• Subjects with a high probability of untreated gastric or esophageal varices or bleeding
• Serious uncontrolled medical comorbidities
• History of liver transplant surgery
• Autoimmune liver disease

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

South Korea · 1 центр

• Yongin Severance Hospital — Yongin-si

Публикации

• Meng L, Xu J, Ye Y, Wang Y, Luo S, Gong X. The Combination of Radiotherapy With Immunotherapy and Potential Predictive Biomarkers for Treatment of Non-Small Cell Lung Cancer Patients. Front Immunol. 2021 Sep 21;12:723609. doi: 10.3389/fimmu.2021.723609. eCollection 2021. PMID 34621270
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• Byun HK, Kim N, Park S, Seong J. Acute severe lymphopenia by radiotherapy is associated with reduced overall survival in hepatocellular carcinoma. Strahlenther Onkol. 2019 Nov;195(11):1007-1017. doi: 10.1007/s00066-019-01462-5. Epub 2019 Apr 15. PMID 30989242
• Theelen WSME, Peulen HMU, Lalezari F, van der Noort V, de Vries JF, Aerts JGJV, Dumoulin DW, Bahce I, Niemeijer AN, de Langen AJ, Monkhorst K, Baas P. Effect of Pembrolizumab After Stereotactic Body Radiotherapy vs Pembrolizumab Alone on Tumor Response in Patients With Advanced Non-Small Cell Lung Cancer: Results of the PEMBRO-RT Phase 2 Randomized Clinical Trial. JAMA Oncol. 2019 Sep 1;5(9):1276- PMID 31294749
• Luke JJ, Lemons JM, Karrison TG, Pitroda SP, Melotek JM, Zha Y, Al-Hallaq HA, Arina A, Khodarev NN, Janisch L, Chang P, Patel JD, Fleming GF, Moroney J, Sharma MR, White JR, Ratain MJ, Gajewski TF, Weichselbaum RR, Chmura SJ. Safety and Clinical Activity of Pembrolizumab and Multisite Stereotactic Body Radiotherapy in Patients With Advanced Solid Tumors. J Clin Oncol. 2018 Jun 1;36(16):1611-1618. PMID 29437535
• Benedict SH, Yenice KM, Followill D, Galvin JM, Hinson W, Kavanagh B, Keall P, Lovelock M, Meeks S, Papiez L, Purdie T, Sadagopan R, Schell MC, Salter B, Schlesinger DJ, Shiu AS, Solberg T, Song DY, Stieber V, Timmerman R, Tome WA, Verellen D, Wang L, Yin FF. Stereotactic body radiation therapy: the report of AAPM Task Group 101. Med Phys. 2010 Aug;37(8):4078-101. doi: 10.1118/1.3438081. PMID 20879569
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Идентификаторы

NCT: NCT06595108 · 09-2024-0026

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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