Pre-Incisional Ketorolac for Patients Undergoing Surgery for Non-Small Cell Lung Cancer and Renal Cell Carcinoma

NCT ID: NCT04495894

Last Updated: 2025-03-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-24
• Study Completion Date: 2024-02-01

Brief Summary

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.

Detailed Description

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.

Conditions

Non-small Cell Lung Cancer; Renal Cell Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Preoperative Ketorolac

Intervention Type: DRUG

30 mg ketorolac will be administered intravenously 30 minutes prior to incision.

Control Group For Participants with Non-small Cell Lung Carcinoma (NSCLC)

Participants randomized to the control group receiving the standard of care during surgery for stage I/II non-small cell lung carcinoma (NSCLC). Open, video-assisted thoracic surgery, laparoscopy, or robotic surgery are allowed. Standard anesthesia is administered. The concurrent control group is to obtain untreated biologic samples for biologic correlative studies and secondary endpoints.

Group Type: NO_INTERVENTION

No interventions assigned to this group

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.

Group Type: EXPERIMENTAL

Preoperative Ketorolac

Intervention Type: DRUG

30 mg ketorolac will be administered intravenously 30 minutes prior to incision.

Control Group For Participants with renal cell carcinoma (RCC)

Participants randomized to the control group receiving the standard of care during surgery for stage III renal cell carcinoma (RCC). Open, video-assisted thoracic surgery, laparoscopy, or robotic surgery are allowed. Standard anesthesia is administered. The concurrent control group is to obtain untreated biologic samples for biologic correlative studies and secondary endpoints.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Preoperative Ketorolac

30 mg ketorolac will be administered intravenously 30 minutes prior to incision.

Intervention Type: DRUG

Other Intervention Names

Acular; Acuvail

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Viraj Master

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Viraj Master, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Onkar Khullar, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Emory University Hospital Midtown

Atlanta, Georgia, United States

Emory Clinic

Atlanta, Georgia, United States

Emory University Hospital

Atlanta, Georgia, United States

Winship Cancer Institute

Atlanta, Georgia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

STUDY00000205

Identifier Type: -

Identifier Source: org_study_id