A Pilot Study of Biomarker Evaluation and Safety of Pre-Incisional Ketorolac for Patients Undergoing Surgical Resection for Non-Small Cell Lung Cancer and Renal Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 68
- 试验地点
- 4
- 主要终点
- Number of Participants Experiencing Postoperative Renal Failure
研究概览
简要总结
This is a pilot study of biomarker evaluation and safety of pre-incisional ketorolac for patients undergoing surgical resection for non-small cell lung cancer and renal cell carcinoma. There is significant promise in the use of preoperative ketorolac to decrease the inflammatory response after surgical resection of tumors, thereby potentially reducing the risk of distant metastatic tumor spread and improving survival. This research will advance scientific knowledge by studying the safety of a preoperative dose of ketorolac prior to major surgical resection, which needs to be assessed prior to proceeding with a larger phase II study designed to evaluate traditional efficacy endpoints such as recurrence and overall survival.
详细描述
Surgical resection is a cornerstone of standard-of-care treatment for early-stage non-small cell lung carcinoma (NSCLC) and renal cell carcinoma (RCC). Yet despite optimal treatment, many of these patients will develop cancer recurrence within the first few years. For example, the 5-year survival rate for patients with stage I/II NSCLC is only around 55%. As a result, more effective treatments that decrease cancer recurrence and increase survival are still needed.
Surgery induces inflammation, immunosuppression and angiogenesis. Although these processes are important for wound healing in response to tissue injury caused by surgery, they also support the survival, growth and dissemination of any remaining cancer cells and can lead to systemic recurrence soon after surgery. Surgical trauma increases the production of prostaglandins and thromboxanes, which have tumor-promoting and immunosuppressive activities, and reduces the activity of natural killer cells, which impairs the ability of the immune system to keep cancer cells in check. However, if given just before tissue injury, non-steroidal anti-inflammatory drugs (NSAIDs) may be able to block the production of prostaglandins/thromboxanes and boost the activity of natural killer cells, and thereby decrease the risk of cancer recurrence. NSAIDs such as ketorolac are already routinely given to cancer patients postoperatively for pain management and are sometimes given intraoperatively (immediately before or during surgery) to prevent postoperative pain. A retrospective clinical analysis found that intraoperative intravenous ketorolac or diclofenac (another NSAID), when added to standard of care for patients with stage I/II NSCLC, was associated with decreased risks of distant recurrence and mortality.
In this study, patients with NSCLC or RCC will be screened and recruited during the preoperative period by the responsible medical and surgical team. Participants will be randomized on the day of surgery to either the preoperative ketorolac group or a concurrent control group who will not receive preincisional ketorolac. Participants will be followed for 28 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pathology-proven or suspected stage 1 or 2 NSCLC and Stage 3 tumor stage 3, node stage 0 (T3N0) RCC, that require surgical resection as the treatment of choice
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- •Ability to understand and the willingness to sign an informed written consent
排除标准
- •Individuals with pure lung ground-glass opacity (GGO) lesions or mixed GGO with <50% solid component
- •Patients undergoing pneumonectomy
- •History of cancer in the 3 years prior to surgery (except for basal-cell carcinoma of the skin or cervical neoplasia).
- •Contraindication for NSAIDs, including peptic ulcer disease, preoperative chronic kidney disease with estimated glomerular filtration rate (eGFR) <45, allergies or intolerance to NSAIDs, coagulation disorder, or age > 80 years
- •Having taken an NSAID within 5 days prior to surgery
- •Immunocompromised status
- •Refusal or inability to understand the protocol and consent form or to receive follow-up in line with the recommendations
- •Preoperative hemoglobin < 9.0
研究组 & 干预措施
Preoperative Ketorolac For Participants with Non-small Cell Lung Carcinoma (NSCLC)
Participants randomized to receive ketorolac prior to surgery for stage I/II non-small cell lung carcinoma (NSCLC). Participants receive standard-of-care surgery. Open, video-assisted thoracic surgery, laparoscopy, or robotic surgery are allowed. Standard anesthesia is administered.
干预措施: Preoperative Ketorolac (Drug)
Preoperative Ketorolac For Participants with renal cell carcinoma (RCC)
Participants randomized to receive ketorolac prior to surgery for stage III renal cell carcinoma (RCC). Participants receive standard-of-care surgery. Open, video-assisted thoracic surgery, laparoscopy, or robotic surgery are allowed. Standard anesthesia is administered.
干预措施: Preoperative Ketorolac (Drug)
结局指标
主要结局
Number of Participants Experiencing Postoperative Renal Failure
时间窗: Prior to Hospital Discharge (up to 13 days post surgery)
Postoperative renal failure is assessed as the number of participants experiencing renal failure prior to hospital discharge.
Number of Participants Receiving a Blood Transfusion
时间窗: Prior to Hospital Discharge (up to 13 days post surgery)
Hemorrhagic side effects among participants receiving ketorolac preoperatively will be assessed as the need for blood transfusions before being discharged from the hospital after surgery. The need for a blood transfusion is defined as needing two or more units of blood, which are not related to vascular injury due to technical considerations or complications, as determined by the operating surgeon.
Number of Participants Experiencing Clinically Significant Hematoma Development
时间窗: Prior to Hospital Discharge (up to 13 days post surgery)
Post-surgical significant hematoma development is assessed as the number of participants experiencing a hematoma prior to hospital discharge.
Number of Participants Returning to the Operating Room for Bleeding
时间窗: Prior to Hospital Discharge (up to 13 days post surgery)
Post-operative bleeding is assessed at the number of participants needing to return to the operating room for bleeding, as determined by the treating surgeon.
Number of Participants Experiencing Postoperative Morbidity
时间窗: Prior to Hospital Discharge (up to 13 days post surgery)
Postoperative morbidity is assessed as the count of participants experiencing at least one adverse event or serious adverse event from surgery to hospital discharge.
次要结局
未报告次要终点