Clinical trial NCT04495894: Pre-Incisional Ketorolac for Patients Undergoing Surgery for Non-Small Cell Lung Cancer and Renal Cell Carcinoma
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Renal Cell Carcinoma
Keywords: Surgery
Lead sponsor: Emory University
Sponsor class: OTHER
First posted: 2020-08-03
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

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

Primary outcomes:
measure: Number of Participants Receiving a Blood Transfusion
timeFrame: Prior to Hospital Discharge (up to 13 days post surgery)
measure: Number of Participants Experiencing Clinically Significant Hematoma Development
timeFrame: Prior to Hospital Discharge (up to 13 days post surgery)
measure: Number of Participants Returning to the Operating Room for Bleeding
timeFrame: Prior to Hospital Discharge (up to 13 days post surgery)
measure: Number of Participants Experiencing Postoperative Renal Failure
timeFrame: Prior to Hospital Discharge (up to 13 days post surgery)
measure: Number of Participants Experiencing Postoperative Morbidity
timeFrame: Prior to Hospital Discharge (up to 13 days post surgery)
Secondary outcomes:
Other outcomes:
measure: Transcriptome Analysis
timeFrame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
measure: Flow Cytometry
timeFrame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
measure: T-Cell Receptor (TCR) Sequencing
timeFrame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
measure: Single Cell RNA Sequencing
timeFrame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
measure: Interleukin-1 Alpha (IL-1alpha) Levels
timeFrame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
measure: Interleukin-1beta (IL-1β) Levels
timeFrame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
measure: Interleukin-2 (IL-2) Levels
timeFrame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
measure: Interleukin-6 (IL-6) Levels
timeFrame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
measure: Interleukin-8 (IL-8) Levels
timeFrame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
measure: Interleukin-10 (IL-10) Levels
timeFrame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
measure: Interleukin-12p70 (IL-12p70) Levels
timeFrame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
measure: Tumor Necrosis Factor-alpha (TNF-alpha) Levels
timeFrame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
measure: Interferon (INF)-Gamma Levels
timeFrame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
measure: Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) Levels
timeFrame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
measure: Monocyte Chemotactic and Activating Factor (MCAF) Levels
timeFrame: Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
Locations:
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Emory Clinic
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Atlanta
country: United States
facility: Winship Cancer Institute
state: Georgia
Study officials:
affiliation: Emory University
name: Viraj Master, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Emory University
name: Onkar Khullar, MD
role: PRINCIPAL_INVESTIGATOR
References: