Phase IB Study of Atezolizumab and Bevacizumab With SBRT for Unresectable Hepatocellular Carcinoma

Massachusetts General Hospital3 个研究点分布在 1 个国家目标入组 20 人2022年8月23日

适应症Unresectable Hepatocellular Carcinoma

干预措施Atezolizumab Bevacizumab Stereotactic body radiation therapy (SBRT)

概览

阶段: 1 期
干预措施: Atezolizumab
疾病 / 适应症: Unresectable Hepatocellular Carcinoma
发起方: Massachusetts General Hospital
入组人数: 20
试验地点: 3
主要终点: Dose Limiting Toxicity Rate
状态: 招募中
最后更新: 2个月前

概览研究者入排标准研究组 & 干预措施结局指标研究点相似试验

概览

简要总结

This research study is evaluating the safety and tolerability of the drugs atezolizumab and bevacizumab with stereotactic body radiation therapy (SBRT) for treating unresectable hepatocellular carcinoma.

This study involves the following interventions:

Atezolizumab
Bevacizumab
Stereotactic body radiation therapy (SBRT)

详细描述

This is a single-arm phase 1B study designed to evaluate the combination of Atezolizumab and Bevacizumab with stereotactic body radiation therapy (SBRT for treating and limiting the recurrence of unresectable hepatocellular carcinoma. The U.S. Food and Drug Administration (FDA) has approved atezolizumab and bevacizumab for unresectable hepatocellular carcinoma. The FDA has not approved the combination of radiation therapy, atezolizumab, and bevacizumab. Atezolizumab is believed to work by increasing the immune system's response to cancer cells. Bevacizumab is believed to work by inhibiting cancer cells from growing by targeting a specific protein in the cancer cells. Radiation therapy is a standard of care treatment for unresectable hepatocellular carcinoma. Radiation therapy has also been shown to increase the effects of drugs like atezolizumab and bevacizumab. The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. Participants will be in this research study for as long as the study drugs are safe and beneficial to them. Participants will then be followed for up to 5 years. It is expected that about 20-32 people will take part in this research study. Genentech, a biotechnology company, is supporting this research study by providing funding for the study, including the study drugs.

注册库

clinicaltrials.gov

开始日期

2022年8月23日

结束日期

2032年1月31日

最后更新

2个月前

研究类型

Interventional

研究设计

Single Group

性别

All

研究者

发起方

Massachusetts General Hospital

责任方

Principal Investigator

主要研究者

Jennifer Wo

Principal Investigator

Massachusetts General Hospital

入排标准

入选标准

•Participants must have diagnosis of hepatocellular carcinoma (HCC) that is deemed unsuitable for surgical resection, transplant, or radiofrequency ablation (RFA). Participants may have up to 5 lesions with a total maximal tumor dimension of \< 20 cm, and no one lesion \> 15 cm. Diagnosis may be confirmed by at least 1 criteria listed below:
•Histologically or cytologically proven diagnosis of HCC within 180 days prior to study registration.
•At least 1 solid liver lesion or vascular tumor thrombus (involving portal vein, IVC, and/or hepatic vein) \> 1 cm with arterial enhancement and delayed washout on multiphasic CT or MRI. Radiologic imaging evaluation must occur within 28 days prior to study registration.
•Enhancing vascular thrombosis demonstrating arterial enhancement and delayed washout of multiphasic MRI. Radiologic imaging evaluation must occur within 30 days prior to study registration.
•Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm (≥2 cm) by chest x-ray or as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam. See Section 12 (Measurement of Effect) for the evaluation of measurable disease.
•Small volume extrahepatic disease permitted, defined as \<2.0 cm in sum of maximal diameters (e.g. presence of one 1.8 cm metastatic lymph node, or two 0.8 cm lung lesions are allowed). Bony lesions are included in the \<2.0 cm of extrahepatic disease. Note that benign periportal lymphadenopathy is not unusual in the presence of hepatitis and is permitted, even if the sum of enlarged nodes is \> 2.0 cm. Radiologic imaging of chest, abdomen, and pelvis via CT or MRI is required within 28 days prior to study registration. CT with contrast is required unless contrast is contraindicated.
•Participants may have received transarterial chemoembolization (TACE) or drug eluting beads (DEB). A 2 week (14 day) washout period is required prior to initiating study treatment.
•Age ≥18 years at the time of signing informed consent document.
•ECOG performance status 0-
•Child-Pugh A liver function within 7 days of study registration.

排除标准

•Prior systemic therapy
•Prior radiation to the region of the liver that would result in excessive doses to normal tissues due to overlap of RT fields is not allowed. Radiotherapy within 28 days and abdominal/pelvic radiotherapy within 60 days prior to initiation of study treatment are not allowed. Exception for palliative radiotherapy to bone lesions within 7 days prior to initiation of study treatment.
•Prior selective internal radiotherapy (SIRT) or hepatic arterial Yttrium therapy, at any time.
•Direct tumor extension into the stomach, duodenum, small bowel, or large bowel.
•Extrahepatic metastases or malignant nodes (that enhance with typical features of HCC) \> 2 cm, in sum of maximal diameters (e.g. presence of one 2.4 cm metastatic lymph node or two 1.2 cm lung lesions).
•Known fibrolamellar HCC, sarcomatoid HCC, or biphenotypic HCC.
•History of leptomingeal disease.
•GI bleed within 6 months prior to study registration.
•Metastatic disease that involves major airways or blood vessels, or centrally located mediastinal tumor masses (\<30 mm from the carina) of large volume. Participants with vascular invasion of the portal or hepatic veins may be enrolled.
•Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:

研究组 & 干预措施

Stereotactic beam radiation therapy (SBRT) +Atezolizumab + Bevacizumab

Study will begin with a safety lead of 6 participants to determine the maximum tolerated dose (MTD) of Stereotactic beam radiation therapy (SBRT) with atezolizumab and bevacizumab followed by study expansion to 14 more participants after maximum tolerated dose (MTD) is established. Safety Lead-In: 6 cycles/18 weeks (study cycle is 3 weeks/21 days) * Cycle 1: Atezolizumab + Bevacizumab (1x) with Stereotactic beam radiation therapy (SBRT) every 1-3 days * Cycles 2-6: Atezolizumab + Bevacizumab (1x) every 3 weeks Expanded Study: * Cycle 1: Atezolizumab + Bevacizumab (1x) with Stereotactic beam radiation therapy (SBRT) every 1-3 days * Cycles 2-End:Atezolizumab + Bevacizumab (1x) every cycle

干预措施: Atezolizumab