Pilot Study of Soft Tissue Sarcoma Treated With Propranolol and Radiation
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Incidence of adverse events
研究概览
简要总结
This phase I trial tests the safety, tolerability and impact of adding propranolol to standard radiation therapy (RT) before surgery for the treatment of patients with soft tissue sarcoma. Sarcomas are a diverse group of rare tumors arising from connective tissue. Approximately 13,000-16,000 new cases of sarcomas arise in the United States annually. Sarcoma management involves multidisciplinary team decision making and treatment is multimodal utilizing chemotherapy (if needed) and RT prior to surgical intervention. Propranolol is a drug that has been used for many years for high blood pressure by blocking both beta-1 and beta-2 adrenergic receptors. Preclinical data suggests that blocking the beta-2 adrenergic receptors can improve the response to both chemotherapy and radiation. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill tumor cells and shrink tumors. RT before surgery makes the tumor smaller and reduces the amount of tissue that needs to be removed during surgery. Surgery is the most common treatment for soft tissue sarcoma. Giving propranolol with standard RT before surgery may be safe, tolerable and impactful in treating patients with soft tissue carcinoma.
详细描述
PRIMARY OBJECTIVE:
I. To establish the safety and tolerability of adding propranolol to standard RT for soft tissue sarcoma.
SECONDARY OBJECTIVE:
I. To evaluate the response of tumor immune microenvironment to treatments for patients.
OUTLINE:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years old
- •Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
- •Eligible for curative-intent radiation therapy for a soft tissue extremity sarcoma
- •Ability to swallow and retain oral medication
- •Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
- •Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
排除标准
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Known hypersensitivity to propranolol
- •Contraindication to beta-blockers e.g.; uncontrolled depression, unstable angina pectoris, uncontrolled heart failure (New York Heart Association [NYHA] grade III or IV), hypotension (systolic blood pressure < 85 or fasting plasma glucose > 160 mg/dL at screening), symptomatic peripheral arterial disease or Raynaud's syndrome, untreated pheochromocytoma, current nondihydropyridines calcium channel blocker use (such as verapamil, diltiazem) or rhythm control agents such as digoxin and amiodarone. Patients with pacemakers will be excluded
- •Patients cannot be on propranolol and another beta-blocker simultaneously. Patients already on beta-blockers can (with approval and under supervision of their primary care physician and/or cardiologist) may choose to stop their current beta-blocker and switch to propranolol for the duration of the study
- •Pregnant or nursing female participants
- •Unwilling or unable to follow protocol requirements
- •Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug
研究组 & 干预措施
Treatment (propranolol, RT, surgery)
Patients receive propranolol PO BID for 2 weeks prior to standard of care RT (weeks 1 and 2) and then during and after standard of care RT (weeks 3-7). Treatment continues in the absence of disease progression or unacceptable toxicity until the time of standard of care surgery (week 8). Additionally, patients undergo PET scan and/or CT scan during screening and may undergo blood and tissue biopsy sample collection throughout the trial.
干预措施: Biopsy (Procedure)
Treatment (propranolol, RT, surgery)
Patients receive propranolol PO BID for 2 weeks prior to standard of care RT (weeks 1 and 2) and then during and after standard of care RT (weeks 3-7). Treatment continues in the absence of disease progression or unacceptable toxicity until the time of standard of care surgery (week 8). Additionally, patients undergo PET scan and/or CT scan during screening and may undergo blood and tissue biopsy sample collection throughout the trial.
干预措施: Biospecimen Collection (Procedure)
Treatment (propranolol, RT, surgery)
Patients receive propranolol PO BID for 2 weeks prior to standard of care RT (weeks 1 and 2) and then during and after standard of care RT (weeks 3-7). Treatment continues in the absence of disease progression or unacceptable toxicity until the time of standard of care surgery (week 8). Additionally, patients undergo PET scan and/or CT scan during screening and may undergo blood and tissue biopsy sample collection throughout the trial.
干预措施: Computed Tomography (Procedure)
Treatment (propranolol, RT, surgery)
Patients receive propranolol PO BID for 2 weeks prior to standard of care RT (weeks 1 and 2) and then during and after standard of care RT (weeks 3-7). Treatment continues in the absence of disease progression or unacceptable toxicity until the time of standard of care surgery (week 8). Additionally, patients undergo PET scan and/or CT scan during screening and may undergo blood and tissue biopsy sample collection throughout the trial.
干预措施: Positron Emission Tomography (Procedure)
Treatment (propranolol, RT, surgery)
Patients receive propranolol PO BID for 2 weeks prior to standard of care RT (weeks 1 and 2) and then during and after standard of care RT (weeks 3-7). Treatment continues in the absence of disease progression or unacceptable toxicity until the time of standard of care surgery (week 8). Additionally, patients undergo PET scan and/or CT scan during screening and may undergo blood and tissue biopsy sample collection throughout the trial.
干预措施: Propranolol (Drug)
Treatment (propranolol, RT, surgery)
Patients receive propranolol PO BID for 2 weeks prior to standard of care RT (weeks 1 and 2) and then during and after standard of care RT (weeks 3-7). Treatment continues in the absence of disease progression or unacceptable toxicity until the time of standard of care surgery (week 8). Additionally, patients undergo PET scan and/or CT scan during screening and may undergo blood and tissue biopsy sample collection throughout the trial.
干预措施: Radiation Therapy (Radiation)
Treatment (propranolol, RT, surgery)
Patients receive propranolol PO BID for 2 weeks prior to standard of care RT (weeks 1 and 2) and then during and after standard of care RT (weeks 3-7). Treatment continues in the absence of disease progression or unacceptable toxicity until the time of standard of care surgery (week 8). Additionally, patients undergo PET scan and/or CT scan during screening and may undergo blood and tissue biopsy sample collection throughout the trial.
干预措施: Surgical Procedure (Procedure)
结局指标
主要结局
Incidence of adverse events
时间窗: Up to 5 weeks post-surgery
Will evaluate safety and tolerability of adding propranolol to standard radiation therapy for soft tissue sarcoma. Will determine the occurrence of a grade 3 or higher treatment related adverse events. Will summarize using frequencies and relative frequencies, with the grade 3 or higher toxicity rate estimated using a 90% credible region obtained by Jeffrey's prior method. Will summarize toxicities and adverse events (as per Common Terminology Criteria for Adverse Events version 5.0) by attribution and grade using frequencies and relative frequencies.
次要结局
- Ribonucleic acid sequencing(Up to 12 weeks)
- Changes in immune markers(Up to 12 weeks)
- Catecholamines(Up to 12 weeks)
- Metabolites(Up to 12 weeks)