Phase I Dose Escalation Trial of Nitroglycerin in Addition to 5-flourouracil and Radiation Therapy for Neo-adjuvant Treatment of Operable Rectal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- The Number of Participants Experiencing Dose Limiting Toxicities (DLT)
研究概览
简要总结
The purpose of this study is to determine whether topical nitroglycerin in addition to 5-flourouracil and radiation therapy are effective in the treatment of operable rectal cancer.
详细描述
This is an open label, non-randomized, multi-cohort, dose escalation trial to evaluate the safety, tolerability, feasibility and maximum tolerated dose (MTD) of topical nitroglycerin in addition to 5-flourouracil and radiation therapy for neo-adjuvant treatment of, T3-T4 or clinically node positive, operable rectal cancer.
Patients that would otherwise be eligible for concurrent neo-adjuvant chemotherapy with continuous infusion 5-FU, for locally advanced operable rectal cancer, will be assigned to 4 sequential cohorts of 3 different dose levels of nitro glycerin patches (0.2; 0.4; and 0.6 mg/hr). Each cohort will consist of 3 patients. All patients will receive radiation therapy, 45-50 Gy in 25-28 fractions to the pelvis along with continuous infusion 5-FU 225mg/M2 for the duration of the radiation therapy. The radiation therapy will be planned and delivered as per institutional standard of care for the Dallas VAMC radiation oncology department.
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 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Biopsy proven Rectal Adenocarcinoma
- •Histological diagnosis of operable T3-4, or T1-4 node positive, M0 rectal adenocarcinoma using endorectal ultrasound and/or MRI in addition to Computed Tomography (CT) of the chest, abdomen and pelvis for pre-study staging Acceptable alternatives for systemic staging instead of CT chest , abdomen, pelvis are CT abdomen and pelvis plus a Chest X-ray or a PET/CT
- •Ability to give informed consent and willingness to adhere to study protocol
- •Age ≥ 18 years and otherwise eligible to receive medical care at the Dallas VA Medical Center.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
- •Adequate hematological, hepatic and renal function defined as in protocol.
排除标准
- •Any condition that would hamper informed consent or ability to comply with the study protocol
- •Significant history of cardiac disease, e.g. uncontrolled hypertension, unstable angina, decompensated congestive-heart failure, myocardial infarction within the last six months or ventricular arrhythmias requiring medication.
- •Pregnant and lactating women.
- •Patients taking Phosphodiesterase - 5 inhibitors (e.g. Sildenafil, Vardenafil or Tadalafil) and is unable to stop for the duration of the chemoradiotherapy.
研究组 & 干预措施
Nitroglycerin
Dose escalation trial of Nitroglycerin
干预措施: Nitroglycerin 0.2 MG/HR (Drug)
Nitroglycerin
Dose escalation trial of Nitroglycerin
干预措施: Nitroglycerin 0.4 MG/HR (Drug)
Nitroglycerin
Dose escalation trial of Nitroglycerin
干预措施: Nitroglycerin 0.6 MG/HR (Drug)
结局指标
主要结局
The Number of Participants Experiencing Dose Limiting Toxicities (DLT)
时间窗: Up to 4-6 weeks for each dosing cohort
DLT was defined as greater or equal to two instances of grade 3 toxicity, or a single event of grade 4-5 toxicity deemed probably or definitely related to the addition of transdermal neoadjuvant chemoradiation to the standard neoadjuvant chemoradiation
次要结局
- Number of Participants With a Pathological Complete Response (pCR)(Time of surgery (~ 6-9 wks) following the completion of neoadjuvant therapy)
研究者
Jonathan E. Dowell
Professor of Medicine
University of Texas Southwestern Medical Center