A Phase I Trial Combining Papaverine and Stereotactic Body Radiation Therapy for Non-Small Cell Lung Cancer or Lung Metastases
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Maximum-tolerated dose (MTD)
研究概览
简要总结
This phase I trial studies the side effects and how well papaverine hydrochloride and stereotactic radiation therapy body (SBRT) work in treating patients with non-small cell lung cancer. Papaverine hydrochloride may help radiation therapy work better by making tumor cells more sensitive to the radiation therapy. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving papaverine hydrochloride with SBRT may work in treating patients with non-small cell lung cancer.
详细描述
PRIMARY OBJECTIVES:
I. To assess the safety and tolerability of concurrent papaverine hydrochloride (PPV), and lung SBRT in patients with non-small cell lung cancer (NSCLC) or lung metastases.
SECONDARY OBJECTIVES:
I. To assess primary tumor control rate, local control rate, local-regional recurrence free-survival (LRRFS), disease-free survival (DFS), distant-metastasis-free survival (DMFS), and overall survival (OS).
II. To assess whether blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (MRI) studies can predict which patients may respond best to PPV + SBRT, and detect changes in oxygenation before and after PPV administration.
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
- •Histologically or cytologically proven NSCLC for whom SBRT to a single lesion has been chosen as the primary treatment modality (planned dose 50 Gy in 4-5 daily fractions). Patients with lung metastases from solid tumors are eligible.
- •Patients must have a tumor =< 5 cm as defined by computed tomography (CT) largest axial dimension. Presence of adjacent nodules considered neoplastic in the same lobe or other ipsilateral lobe are allowed as long as the nodule(s) can be encompassed in an SBRT gross tumor volume (GTV) of =< 5 cm, within 1 isocenter. Multiple isocenters are not allowed
- •No prior radiation resulting in overlapping fields
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Must be able to undergo correlative research MRIs
- •No active connective tissue disease (scleroderma) or idiopathic pulmonary fibrosis (IPF)
- •No history of complete atrioventricular block, hepatic dysfunction (e.g. cirrhosis), or priapism
- •Within 30 days of registration: patients must have vital signs, history/physical examination, and laboratory studies (liver function tests, creatinine or creatinine clearance assessment)
- •Life expectancy of at least 12 weeks in the opinion of investigator
- •Women of child-bearing potential (WOCBP) must have a negative pregnancy test within 14 days of registration. Urine human chorionic gonadotropin (HCG) is an acceptable pregnancy assessment. Nursing women may participate only if nursing is discontinued, due to the possibility of harm to nursing infants from the treatment regimen
- •Within 90 days of registration: pulmonary function tests (PFTs) including forced expiratory volume in 1 second (FEV-1) and diffusion capacity of the lung for carbon monoxide (DLCO)
- •Albumin >= 2.5 g/dL (within 30 days of study registration)
- •Total bilirubin =< 1.5 x upper limit of normal (ULN) (within 30 days of study registration)
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN (within 30 days of study registration)
- •Creatinine =< 1.5 x ULN or calculated creatinine >= 50 mL/min, calculated by the Cockcroft-Gault formula or 24-hour urine creatinine clearance >= 50 mL/min (within 30 days of study registration)
排除标准
- •History of another malignancy
- •Exception: Subjects who have been disease-free for >= 3 years, or subjects with a history of localized prostate cancer, in situ carcinoma (e.g. breast, cervix, oral cavity), differentiated thyroid neoplasm, completely resected non-melanoma skin cancer, are eligible
- •Any serious and/or unstable pre-existing medical disorder (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with subject?s safety, obtaining informed consent or compliance to the study procedures, in the opinion of the investigator
- •Pregnancy or breastfeeding: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, the duration of study participation and for 4 months after the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. No breastfeeding while patient is on study
- •Patients with history of pneumonectomy
- •Prior cytotoxic chemotherapy, molecularly-targeted agents (e.g. erlotinib, crizotinib), or immunotherapy unless >= 2 weeks from last dose. Patients can start chemotherapy, immunotherapy, or other systemic therapy after completion of SBRT, but this should be planned for ≥ 2 weeks from last SBRT dose.
- •History of active connective tissue disease (scleroderma), idiopathic pulmonary fibrosis, pneumonitis
- •Hepatic insufficiency resulting in jaundice and/or coagulation defects, or not meeting laboratory values (albumin, total bilirubin, AST/ALT)
研究组 & 干预措施
Treatment (BOLD fMRI, papaverine hydrochloride, SBRT)
Patients undergo BOLD fMRI and receive papaverine hydrochloride IV on days -7 to day 1. Within 30-90 minutes, patients undergo a second BOLD fMRI. Patients then receive papaverine hydrochloride IV and within 30-90 minutes after dose undergo SBRT for a up to 4-5 sessions over 2 weeks. Patients undergo CT scan throughout the study and blood sample collection on study.
干预措施: Blood Oxygen Level Dependent Imaging (Procedure)
Treatment (BOLD fMRI, papaverine hydrochloride, SBRT)
Patients undergo BOLD fMRI and receive papaverine hydrochloride IV on days -7 to day 1. Within 30-90 minutes, patients undergo a second BOLD fMRI. Patients then receive papaverine hydrochloride IV and within 30-90 minutes after dose undergo SBRT for a up to 4-5 sessions over 2 weeks. Patients undergo CT scan throughout the study and blood sample collection on study.
干预措施: Papaverine Hydrochloride (Drug)
Treatment (BOLD fMRI, papaverine hydrochloride, SBRT)
Patients undergo BOLD fMRI and receive papaverine hydrochloride IV on days -7 to day 1. Within 30-90 minutes, patients undergo a second BOLD fMRI. Patients then receive papaverine hydrochloride IV and within 30-90 minutes after dose undergo SBRT for a up to 4-5 sessions over 2 weeks. Patients undergo CT scan throughout the study and blood sample collection on study.
干预措施: Stereotactic Body Radiation Therapy (Radiation)
结局指标
主要结局
Maximum-tolerated dose (MTD)
时间窗: Up to 2 weeks
Will employ the Bayesian optimal interval (BOIN) design to find the MTD.
次要结局
- Primary tumor control(At 12 and 24 months after stereotactic body radiation therapy (SBRT) completion)
- Local control rate (primary tumor control + involved lobar control)(Up to 12 months after SBRT completion)
- Local-regional recurrence free-survival(From time of entry onto study until the time of documented local-regional recurrence or death, assessed up to 12 months after SBRT completion)
- Distant metastasis-free survival(Time from entry onto study until the time of documented metastatic recurrence or death, assessed up to 12 months after SBRT treatment)
- Disease-free survival(Time from entry onto study until the time of any documented disease recurrence or death, assessed up to 12 months after SBRT completion)
- Overall survival(Time from study entry until time of death from any cause, assessed up to 12 months after SBRT completion)
- Changes in magnetic resonance imaging (MRI) blood oxygen level-dependent (BOLD) response(Up to 4 hours)
- Change in hypoxia-inducible micro ribonucleic acids (miRNAs)(Up to 3 months)
研究者
Jeremy Brownstein
Principal Investigator
Ohio State University Comprehensive Cancer Center