Non-small Cell Lung CancerPhase 2NCT04495894
Pre-Incisional Ketorolac for Patients Undergoing Surgery for Non-Small Cell Lung Cancer and Renal Cell Carcinoma
A Phase 2 study testing Preoperative Ketorolac in people with Non-small Cell Lung Cancer and Renal Cell Carcinoma, run by Emory University at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Non-small Cell Lung Cancer, Renal Cell Carcinoma
- What is being tested?
- Preoperative Ketorolac
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 4 sitesUnited States
- Study dates
- 24 Aug 2020to 1 Feb 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Emory University Hospital Midtown
Atlanta, Georgia, 30308
Emory Clinic
Atlanta, Georgia, 30322
Emory University Hospital
Atlanta, Georgia, 30322
Winship Cancer Institute
Atlanta, Georgia, 30322
About this study
Official title: 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.
Read the 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
- Being tested
- Preoperative Ketorolac
- Keywords
- Surgery
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Preoperative KetorolacDrug
Also called Acular, Acuvail
30 mg ketorolac will be administered intravenously 30 minutes prior to incision.
| Study group | Role | What they receive |
|---|---|---|
| Preoperative Ketorolac For Participants with Non-small Cell Lung Carcinoma (NSCLC) | Experimental | 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. Receives: Drug: Preoperative Ketorolac |
| Control Group For Participants with Non-small Cell Lung Carcinoma (NSCLC) | No intervention | 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. |
| Preoperative Ketorolac For Participants with renal cell carcinoma (RCC) | Experimental | 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. Receives: Drug: Preoperative Ketorolac |
| Control Group For Participants with renal cell carcinoma (RCC) | No intervention | 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 being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Receiving a Blood Transfusion
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.
Measured: Prior to Hospital Discharge (up to 13 days post surgery)
Number of Participants Experiencing Clinically Significant Hematoma Development
Post-surgical significant hematoma development is assessed as the number of participants experiencing a hematoma prior to hospital discharge.
Measured: Prior to Hospital Discharge (up to 13 days post surgery)
Number of Participants Returning to the Operating Room for Bleeding
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.
Measured: Prior to Hospital Discharge (up to 13 days post surgery)
Number of Participants Experiencing Postoperative Renal Failure
Postoperative renal failure is assessed as the number of participants experiencing renal failure prior to hospital discharge.
Measured: Prior to Hospital Discharge (up to 13 days post surgery)
Number of Participants Experiencing Postoperative Morbidity
Postoperative morbidity is assessed as the count of participants experiencing at least one adverse event or serious adverse event from surgery to hospital discharge.
Measured: Prior to Hospital Discharge (up to 13 days post surgery)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2020
- Study start24 Aug 2020
- Primary completion1 Feb 2024
- Study completion1 Feb 2024
Why it stopped: This study was terminated after interim analyses showed no benefits.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non-small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Viraj Master, Emory University
- Investigators
- Viraj Master, MD, PhD, Principal investigator, Emory UniversityOnkar Khullar, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04495894
- Sponsor's protocol ID
- STUDY00000205
- Status last verified
- Feb 2025
- First submitted
- 29 Jul 2020
- Last updated
- 4 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04495894
- Acronym / sponsor ID
- STUDY00000205
- Conditions
- Non-small Cell Lung Cancer, Renal Cell Carcinoma
- Keywords
- Surgery
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This study was terminated after interim analyses showed no benefits.
- Enrolment
- 68 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Study start
- 24 Aug 2020 (actual)
- Primary completion
- 1 Feb 2024 (actual)
- Study completion
- 1 Feb 2024 (actual)
- First posted
- 3 Aug 2020 (actual)
- Results
- Posted 4 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Preoperative Ketorolac For Participants with Non-small Cell Lung Carcinoma (NSCLC) | Experimental | Drug: Preoperative KetorolacParticipants 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. |
| Control Group For Participants with Non-small Cell Lung Carcinoma (NSCLC) | No intervention | –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. |
| Preoperative Ketorolac For Participants with renal cell carcinoma (RCC) | Experimental | Drug: Preoperative KetorolacParticipants 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. |
| Control Group For Participants with renal cell carcinoma (RCC) | No intervention | –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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Preoperative KetorolacAlso: Acular, Acuvail30 mg ketorolac will be administered intravenously 30 minutes prior to incision. | Drug | Preoperative Ketorolac For Participants with Non-small Cell Lung Carcinoma (NSCLC), Preoperative Ketorolac For Participants with renal cell carcinoma (RCC) |
Primary outcome
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.
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.
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.
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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Viraj Master, MD, PhD principal investigator
Emory University
Onkar Khullar, MD principal investigator
Emory University
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Preoperative Ketorolac in people with Non-small Cell Lung Cancer and Renal Cell Carcinoma, run by Emory University at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Receiving a Blood Transfusion (time frame: Prior to Hospital Discharge (up to 13 days post surgery)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2025.