Lidocaine Infusion for Pancreatic Cancer

Overseen By Gina E. Votta-Velis, MD PhD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Illinois at Chicago

Must not be taking: Class I antiarrhythmics, Amiodarone

Disqualifiers: Heart block, Sinoatrial block, HIV, others

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 hours

46 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently taking certain heart medications like quinidine, flecainide, disopyramide, or procainamide, or if you have been treated with amiodarone in the past.

What data supports the effectiveness of the drug lidocaine for pancreatic cancer?

A study found that intravenous lidocaine during pancreatic cancer surgery is linked to reduced opioid use and may improve long-term survival, suggesting potential benefits for patients undergoing surgery. ^{1 2 3 4 5}

Is lidocaine safe for use in humans?

Lidocaine is generally safe for use in humans, but there are risks of overdose, especially in children, when used in high doses or frequently. It has been used safely in various forms for pain relief, but caution is needed to avoid toxic reactions, particularly with viscous lidocaine. ^{6 7 8 9 10}

How is the drug lidocaine used in treating pancreatic cancer different from other treatments?

Lidocaine infusion for pancreatic cancer is unique because it is administered intravenously during surgery and may improve long-term survival by reducing inflammation and possibly having anti-tumor effects, unlike standard treatments that primarily focus on chemotherapy or radiation. ^{1 6 11 12 13}

What is the purpose of this trial?

This study elucidates the effects of the intravenous (IV) lidocaine infusion on the biology of pancreatic circulating tumor cells (CTCs) isolated from patients undergoing robotic pancreatectomy for all types of pancreatic cancer. A prospective randomized controlled double blinded trial design will be used for the proposed study.

Research Team

Gina E. Votta-Velis, MD PhD

Principal Investigator

Associate Professor

Eligibility Criteria

This trial is for patients with pancreatic cancer that was initially thought to be removable but found to have spread at surgery. They may have had previous treatments like chemo. Participants must understand and sign a consent form, and their cancer should be measurable by certain medical criteria.

Inclusion Criteria

My cancer was thought to be removable but was found to have spread during surgery.

I have read, understood, and signed the approved consent form.

I have at least one tumor that can be measured.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a 24-hour lidocaine infusion or a saline infusion during the perioperative period

24 hours

In-hospital during surgery

Follow-up

Participants are monitored for safety and effectiveness after treatment, with blood samples collected perioperatively

1-2 weeks

Treatment Details

Interventions

• Lidocaine Hydrochloride

Trial Overview The study is testing the effects of IV lidocaine (a local anesthetic) on circulating tumor cells in patients undergoing robotic surgery for pancreatic cancer. It's a controlled experiment where neither doctors nor patients know who gets lidocaine or a saline placebo.

Participant Groups

Group I: Lidocaine Hydrochloride Experimental Treatment 1 Intervention

The IV bolus and infusions of lidocaine to those patients assigned to the lidocaine group will be started in the operating room and will continue until 24 h later. The group receiving the lidocaine infusion will first be administered a 1.0 - 1.5 mg/kg loading infusion over 5 minutes followed by a 1.0 - 1.5 mg/kg/h infusion for 24 h

Group II: Saline Solution for Injection Placebo Group 1 Intervention

The group receiving the saline infusion will be administered an equivalent volume of saline infused over 5 min followed by a saline infusion at the same flow rate as that used in the lidocaine group for 24 h (1.0 - 1.5 mg/kg/hr)

Lidocaine Hydrochloride is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Xylocaine for:

• Local anesthesia
• Regional anesthesia
• Heart arrhythmia
• Post-herpetic neuralgia

Approved in United States as Lidocaine for:

• Local anesthesia
• Regional anesthesia
• Heart arrhythmia
• Post-herpetic neuralgia
• Skin graft donor site pain

Approved in Canada as Xylocaine for:

• Local anesthesia
• Regional anesthesia
• Heart arrhythmia

Approved in Japan as Lidocaine for:

• Local anesthesia
• Regional anesthesia

Who Is Running the Clinical Trial?

University of Illinois at Chicago

Lead Sponsor

Trials

653

Recruited

1,574,000+

Findings from Research

In a double-blind, cross-over study involving 10 cancer patients with cutaneous allodynia, intravenous lidocaine provided complete pain relief for one patient and partial relief for another, but overall, it did not significantly reduce pain intensity compared to placebo.

The study concluded that intravenous lidocaine is not recommended as a routine treatment for pain in cancer patients with cutaneous allodynia, highlighting the need for further research on its effects with different types of pain stimuli.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trial of intravenous lidocaine on painful neuropathy in cancer patients. Ellemann, K., Sjögren, P., Banning, AM., et al.[2019]

Lidocaine hydrochloride 3.5% ophthalmic gel achieves maximum concentration in ocular tissues within 20 minutes of application, indicating rapid onset of action for topical ocular anesthesia.

The gel demonstrates high intraocular penetration with significantly lower systemic exposure, making it an effective and safe local anesthetic for ophthalmic procedures, with longer elimination half-lives in ocular tissues compared to plasma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocular and systemic pharmacokinetics of lidocaine hydrochloride ophthalmic gel in rabbits after topical ocular administration. Liu, B., Ding, L., Xu, X., et al.[2022]

In a survey of 437 dermatologic surgeons, the average volume of 1% lidocaine used for facial skin cancer excision was 3.44 mL, and for reconstruction, it was 11.70 mL, indicating that the amounts used are modest and within safe limits.

No cases of lidocaine toxicity were reported, and the incidence of mild adverse events related to anesthesia was very low (greater than 0.15%), suggesting that lidocaine is a safe option for local anesthesia in dermatologic procedures compared to general anesthesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Local Intracutaneous Lidocaine Anesthesia Used by Dermatologic Surgeons for Skin Cancer Excision and Postcancer Reconstruction: Quantification of Standard Injection Volumes and Adverse Event Rates. Alam, M., Schaeffer, MR., Geisler, A., et al.[2022]

In a study involving 30 children aged 4-8 years, buccal infiltration with articaine was found to cause less pain and discomfort compared to the traditional inferior alveolar nerve block (IANB) with lignocaine during pulp therapy for primary mandibular second molars.

The results indicated that articaine infiltration not only provided effective anesthesia but also allowed for a more positive patient experience, suggesting it as a preferable alternative to IANB in pediatric dentistry.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing the Pain Reaction of Children and Evaluation of Efficacy of Buccal Infiltration with Articaine and Inferior Alveolar Nerve Block with Lignocaine for Pulp Therapy in Primary Mandibular Second Molars. Daneswari, V., Venugopal Reddy, N., Madhavi, G., et al.[2022]

Intraoperative intravenous lidocaine significantly reduced the consumption of opioids during surgery and was associated with improved overall survival rates in patients undergoing pancreatic cancer surgery, with 1-year survival rates of 68.0% compared to 62.6% in the non-lidocaine group.

While there was no significant difference in disease-free survival or length of stay between the lidocaine and non-lidocaine groups, the use of lidocaine was linked to a prolonged overall survival, suggesting it may enhance long-term outcomes after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between intraoperative intravenous lidocaine infusion and survival in patients undergoing pancreatectomy for pancreatic cancer: a retrospective study. Zhang, H., Yang, L., Zhu, X., et al.[2020]

The needle-free powder lidocaine delivery system provided significantly better pain relief compared to a sham placebo in pediatric patients undergoing venipuncture, as shown by lower pain scores on the Wong-Baker FACES scale (P = 0.0022).

The treatment was well tolerated with only minor side effects, such as erythema and petechiae, and no serious adverse events were reported, indicating it is a safe option for providing analgesia in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of a Needle-free Powder Lidocaine Delivery System in Pediatric Patients Undergoing Venipuncture or Peripheral Venous Cannulation: Randomized Double-blind COMFORT-004 Trial. Schmitz, ML., Zempsky, WT., Meyer, JM.[2018]

Viscous lidocaine can pose a high risk of overdose in pediatric patients due to their altered pharmacokinetics, making doses safe for adults potentially toxic for children.

Benzocaine is recommended as a safer alternative for treating painful mouth lesions in children, as it has a lower incidence of side effects, but if lidocaine must be used, clear and specific dosing instructions should be provided to parents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lidocaine overdose: another preventable case? Gonzalez del Rey, J., Wason, S., Druckenbrod, RW.[2019]

A case of lidocaine toxicity was reported in a 22-year-old man who used over 240 ml of oral viscous lidocaine daily for severe tongue ulcers, highlighting the risk of overdose even when serum levels are below toxic thresholds.

The persistence of toxic symptoms despite lower serum lidocaine levels suggests that metabolites of lidocaine may also play a role in toxicity, indicating the need for careful monitoring in patients using viscous lidocaine frequently.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lidocaine toxicity during frequent viscous lidocaine use for painful tongue ulcer. Yamashita, S., Sato, S., Kakiuchi, Y., et al.[2019]

Lidocaine hydrochloride gel is shown to be at least as effective as other anesthetic methods for pain control during various ophthalmic surgeries, with a longer duration of action compared to topical drops, based on a review of 26 studies involving 1167 participants.

Patient and surgeon satisfaction with lidocaine gel is high, and adverse effects are rare and similar to those associated with traditional anesthetic drops, indicating it is a safe option for ocular anesthesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, efficacy, and patient acceptability of lidocaine hydrochloride ophthalmic gel as a topical ocular anesthetic for use in ophthalmic procedures. Page, MA., Fraunfelder, FW.[2021]

In a study of four pediatric oncology patients aged 8 to 18, continuous lidocaine infusions significantly reduced pain scores from a median of 8/10 to 2/10 during treatment, indicating its efficacy in managing severe, opioid-refractory cancer pain.

The infusions were generally well tolerated with minimal side effects, and pain relief often persisted beyond the infusion period, suggesting a potential long-term modulation effect on pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuous Lidocaine Infusions to Manage Opioid-Refractory Pain in a Series of Cancer Patients in a Pediatric Hospital. Gibbons, K., DeMonbrun, A., Beckman, EJ., et al.[2017]

The lidocaine-epirubicin-lipiodol emulsion showed higher concentrations of lidocaine in tumor tissues compared to the control group, indicating effective delivery and sustained release of lidocaine during TACE procedures.

Patients receiving the emulsion (Group B) reported significantly lower pain levels and required less additional analgesics compared to those receiving a bolus injection (Group A), demonstrating both the efficacy and safety of this method for pain control in TACE for hepatocellular carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraarterial Lidocaine Administration for Pain Control by Water-in-Oil Technique in Transarterial Chemoembolization: in vivo and Randomized Clinical Trial. Wang, LZ., Hu, XX., Shen, XC., et al.[2022]

Intra-arterial infusion of lidocaine into the celiac trunk significantly reduced the severity of cerulein-induced acute pancreatitis in Wistar rats, as evidenced by lower serum levels of pancreatic enzymes amylase and lipase compared to the control group.

Histopathological analysis showed that lidocaine treatment led to less severe pancreatic damage, highlighting the importance of early vasodilation in managing acute pancreatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of intra-arterial lidocaine infusion in the treatment of cerulein-induced acute pancreatitis. Antkowiak, R., Antkowiak, Ł., Grzegorczyn, S., et al.[2020]

In a study of 563 patients undergoing surgery for pancreatic cancer, intravenous lidocaine did not improve overall or disease-free survival after pancreatectomy, indicating it may not be an effective intervention for enhancing long-term outcomes in this context.

However, lidocaine infusion significantly reduced the need for intraoperative opioids and decreased circulating neutrophil extracellular traps (NETs) post-surgery, suggesting some benefits in pain management and inflammation, even though it did not affect tumor-associated NETs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative lidocaine infusion in patients undergoing pancreatectomy for pancreatic cancer: a mechanistic, multicentre randomised clinical trial. Zhang, H., Qu, M., Guo, K., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Trial of intravenous lidocaine on painful neuropathy in cancer patients. [2019]

2. France pubmed.ncbi.nlm.nih.gov

Ocular and systemic pharmacokinetics of lidocaine hydrochloride ophthalmic gel in rabbits after topical ocular administration. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Safety of Local Intracutaneous Lidocaine Anesthesia Used by Dermatologic Surgeons for Skin Cancer Excision and Postcancer Reconstruction: Quantification of Standard Injection Volumes and Adverse Event Rates. [2022]

4. India pubmed.ncbi.nlm.nih.gov

Assessing the Pain Reaction of Children and Evaluation of Efficacy of Buccal Infiltration with Articaine and Inferior Alveolar Nerve Block with Lignocaine for Pulp Therapy in Primary Mandibular Second Molars. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Association between intraoperative intravenous lidocaine infusion and survival in patients undergoing pancreatectomy for pancreatic cancer: a retrospective study. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of a Needle-free Powder Lidocaine Delivery System in Pediatric Patients Undergoing Venipuncture or Peripheral Venous Cannulation: Randomized Double-blind COMFORT-004 Trial. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Lidocaine overdose: another preventable case? [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Lidocaine toxicity during frequent viscous lidocaine use for painful tongue ulcer. [2019]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Safety, efficacy, and patient acceptability of lidocaine hydrochloride ophthalmic gel as a topical ocular anesthetic for use in ophthalmic procedures. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Continuous Lidocaine Infusions to Manage Opioid-Refractory Pain in a Series of Cancer Patients in a Pediatric Hospital. [2017]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Intraarterial Lidocaine Administration for Pain Control by Water-in-Oil Technique in Transarterial Chemoembolization: in vivo and Randomized Clinical Trial. [2022]

12. Poland pubmed.ncbi.nlm.nih.gov

Efficacy of intra-arterial lidocaine infusion in the treatment of cerulein-induced acute pancreatitis. [2020]

13. England pubmed.ncbi.nlm.nih.gov

Intraoperative lidocaine infusion in patients undergoing pancreatectomy for pancreatic cancer: a mechanistic, multicentre randomised clinical trial. [2023]