Clinical Trials /

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

NCT04495894

Description:

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. A total of 56 patients (28 per disease site) will be enrolled into the experimental arm and will receive ketorolac prior to surgery. About 10 patients will be allocated randomly into a control group, for each disease site, for a total of 76 patients enrolled. The 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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
  • Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: STUDY00000205
  • NCT ID: NCT04495894

Conditions

  • Non-small Cell Lung Cancer
  • Renal Cell Carcinoma

Interventions

DrugSynonymsArms
Preoperative KetorolacAcular, AcuvailPreoperative Ketorolac

Purpose

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. A total of 56 patients (28 per disease site) will be enrolled into the experimental arm and will receive ketorolac prior to surgery. About 10 patients will be allocated randomly into a control group, for each disease site, for a total of 76 patients enrolled. The 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.

      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.

      Patients will be screened and recruited during the preoperative period by the responsible
      medical and surgical team. Blood will be drawn preoperatively and then at the end of the
      surgical procedure. Participants will be randomized to either preoperative ketorolac group or
      a concurrent control group who will not receive preincisional ketorolac. The concurrent
      control group is to obtain untreated biologic samples for biologic correlative studies and
      secondary endpoints. These patients will not be compared to the investigational cohort in
      regards to the primary endpoint of safety. Patients will be randomized on the day of surgery
      to either the experimental or control arms and participants will be followed or 28 days.
      Medical records will be reviewed at 1 and 2 years post-surgery for survival assessment.
    

Trial Arms

NameTypeDescriptionInterventions
Preoperative KetorolacExperimentalParticipants randomized to receive ketorolac prior to surgery for stage I/II NSCLC and stage III RCC. Participants will receive standard-of-care surgery. Open, video-assisted thoracic surgery, laparoscopy, or robotic surgery are allowed. Standard anesthesia will be administered.
  • Preoperative Ketorolac
Control GroupNo InterventionParticipants randomized to the control group receiving the standard of care during surgery for stage I/II NSCLC and stage III RCC. Open, video-assisted thoracic surgery, laparoscopy, or robotic surgery are allowed. Standard anesthesia will be administered. The concurrent control group is to obtain untreated biologic samples for biologic correlative studies and secondary endpoints.

    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) <60, 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
          
    Maximum Eligible Age:80 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Incidence of Blood Transfusion Among Ketorolac Group
    Time Frame:Prior to Hospital Discharge (generally up to 7 days post surgery)
    Safety Issue:
    Description: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 greater than two units of blood, which are not related to vascular injury due to technical considerations or complications, as determined by the operating surgeon.

    Secondary Outcome Measures

    Measure:Change in Interleukin-1 alpha (IL-1alpha) Levels
    Time Frame:Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
    Safety Issue:
    Description:IL-1alpha levels will be compared between study arms.
    Measure:Change in Interleukin-1beta (IL-1β) Levels
    Time Frame:Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
    Safety Issue:
    Description:IL-1beta levels will be compared between study arms.
    Measure:Change in Interleukin-2 (IL-2) Levels
    Time Frame:Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
    Safety Issue:
    Description:IL-2 levels will be compared between study arms.
    Measure:Change in Interleukin-6 (IL-6) Levels
    Time Frame:Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
    Safety Issue:
    Description:IL-6 levels will be compared between study arms.
    Measure:Change in Interleukin-8 (IL-8) Levels
    Time Frame:Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
    Safety Issue:
    Description:IL-8 levels will be compared between study arms.
    Measure:Change in Interleukin-10 (IL-10) Levels
    Time Frame:Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
    Safety Issue:
    Description:IL-10 levels will be compared between study arms.
    Measure:Change in Interleukin-12p70 (IL-12p70) Levels
    Time Frame:Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
    Safety Issue:
    Description:IL-12p70 levels will be compared between study arms.
    Measure:Change in Tumor Necrosis Factor-alpha (TNF-alpha) Levels
    Time Frame:Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
    Safety Issue:
    Description:TNF-alpha levels will be compared between study arms.
    Measure:Change in Interferon (INF)-gamma Levels
    Time Frame:Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
    Safety Issue:
    Description:INF-gamma levels will be compared between study arms.
    Measure:Change in Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) Levels
    Time Frame:Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
    Safety Issue:
    Description:GM-CSF levels will be compared between study arms.
    Measure:Change in Monocyte Chemotactic and Activating Factor (MCAF) Levels
    Time Frame:Baseline, Day 1, Day 3 (if admitted to hospital), Day 7, Day 28
    Safety Issue:
    Description:MCAF levels will be compared between study arms.

    Details

    Phase:Early Phase 1
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:Emory University

    Trial Keywords

    • Surgery

    Last Updated

    July 29, 2020