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

February 26, 2025 updated by: Viraj Master, Emory University

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
68

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital
      • Atlanta, Georgia, United States, 30308
        • Emory University Hospital Midtown
      • Atlanta, Georgia, United States, 30322
        • Emory Clinic
      • Atlanta, Georgia, United States, 30322
        • Winship Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Drug: Preoperative Ketorolac
30 mg ketorolac will be administered intravenously 30 minutes prior to incision.
Other Names:
  • Acular
  • Acuvail
No Intervention: 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.
Experimental: 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.
Drug: Preoperative Ketorolac
30 mg ketorolac will be administered intravenously 30 minutes prior to incision.
Other Names:
  • Acular
  • Acuvail
No Intervention: 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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants Receiving a Blood Transfusion
Time Frame: 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.
Prior to Hospital Discharge (up to 13 days post surgery)
Number of Participants Experiencing Clinically Significant Hematoma Development
Time Frame: 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.
Prior to Hospital Discharge (up to 13 days post surgery)
Number of Participants Returning to the Operating Room for Bleeding
Time Frame: 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.
Prior to Hospital Discharge (up to 13 days post surgery)
Number of Participants Experiencing Postoperative Renal Failure
Time Frame: 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.
Prior to Hospital Discharge (up to 13 days post surgery)
Number of Participants Experiencing Postoperative Morbidity
Time Frame: 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.
Prior to Hospital Discharge (up to 13 days post surgery)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Interleukin-1 alpha (IL-1alpha) Levels
Time Frame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
IL-1alpha levels will be compared between study arms.
Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
Interleukin-1beta (IL-1β) Levels
Time Frame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
IL-1beta levels will be compared between study arms.
Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
Interleukin-2 (IL-2) Levels
Time Frame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
IL-2 levels will be compared between study arms.
Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
Interleukin-6 (IL-6) Levels
Time Frame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
IL-6 levels will be compared between study arms.
Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
Interleukin-8 (IL-8) Levels
Time Frame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
IL-8 levels will be compared between study arms.
Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
Interleukin-10 (IL-10) Levels
Time Frame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
IL-10 levels will be compared between study arms.
Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
Interleukin-12p70 (IL-12p70) Levels
Time Frame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
IL-12p70 levels will be compared between study arms.
Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
Tumor Necrosis Factor-alpha (TNF-alpha) Levels
Time Frame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
TNF-alpha levels will be compared between study arms.
Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
Interferon (INF)-gamma Levels
Time Frame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
INF-gamma levels will be compared between study arms.
Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) Levels
Time Frame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
GM-CSF levels will be compared between study arms.
Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
Monocyte Chemotactic and Activating Factor (MCAF) Levels
Time Frame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
MCAF levels will be compared between study arms.
Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Interleukin-1beta (IL-1β) Levels
Time Frame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
IL-1beta levels will be compared between study arms.
Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
Interleukin-2 (IL-2) Levels
Time Frame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
IL-2 levels will be compared between study arms.
Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
Interleukin-6 (IL-6) Levels
Time Frame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
IL-6 levels will be compared between study arms.
Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
Interleukin-8 (IL-8) Levels
Time Frame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
IL-8 levels will be compared between study arms.
Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
Interleukin-10 (IL-10) Levels
Time Frame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
IL-10 levels will be compared between study arms.
Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
Interleukin-12p70 (IL-12p70) Levels
Time Frame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
IL-12p70 levels will be compared between study arms.
Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
Tumor Necrosis Factor-alpha (TNF-alpha) Levels
Time Frame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
TNF-alpha levels will be compared between study arms.
Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) Levels
Time Frame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
GM-CSF levels will be compared between study arms.
Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
Monocyte Chemotactic and Activating Factor (MCAF) Levels
Time Frame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
MCAF levels will be compared between study arms.
Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
Transcriptome Analysis
Time Frame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
Transcriptome analysis will be performed to evaluate the effects of ketorolac on immune response pathways.
Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
Flow Cytometry
Time Frame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
Flow Cytometry will be performed to evaluate the effects of ketorolac on immune response pathways.
Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
T-Cell Receptor (TCR) Sequencing
Time Frame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
T-Cell receptor (TCR) sequencing will be performed to evaluate the effects of ketorolac on immune response pathways.
Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
Single Cell RNA Sequencing
Time Frame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
Single cell RNA sequencing will be performed to evaluate the effects of ketorolac on immune response pathways.
Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
Interleukin-1 Alpha (IL-1alpha) Levels
Time Frame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
IL-1alpha levels will be compared between study arms.
Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
Interferon (INF)-Gamma Levels
Time Frame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
INF-gamma levels will be compared between study arms.
Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Emory University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Viraj Master, MD, PhD, Emory University
  • Principal Investigator: Onkar Khullar, MD, Emory University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 24, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 29, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 29, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 3, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 26, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • STUDY00000205

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data which will be available for sharing includes renal function data, complications of surgery, and immune correlates.

IPD Sharing Time Frame

Data will be available for sharing once results from this study are published.

IPD Sharing Access Criteria

Data will be available for validation analyses.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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