Gabapentin + Ketamine for Head and Neck Cancer Pain Management

Overseen By Vanderbilt-Ingram Service for Timely Access

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Dianne Lou

Must not be taking: Gabapentin, Ketamine

Disqualifiers: Seizure disorder, Schizophrenia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days

64 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine a safe and effective dose of gabapentin and ketamine for managing pain in individuals with head and neck cancer undergoing chemoradiation (a combination of chemotherapy and radiation therapy). Participants take gabapentin (commonly used for nerve pain) and ketamine (an anesthetic and pain reliever) three times daily to assess their ability to prevent treatment-related pain. This study may suit individuals diagnosed with locally advanced head and neck cancer who are about to begin chemoradiation and are not currently taking gabapentin or ketamine. As a Phase 1, Phase 2 trial, the research focuses on understanding the treatment's effects and measuring its effectiveness in an initial, smaller group.

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 gabapentin or ketamine.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that combining gabapentin and ketamine is being tested to help manage pain in patients with head and neck cancer. Previous patients have generally tolerated this combination well. Early studies reported some side effects, mostly mild to moderate. While some discomfort might occur, severe reactions are not expected.

Gabapentin is already approved for other uses, such as treating nerve pain. Ketamine is also used for pain and is considered safe in controlled settings. The current study aims to find the best dose that is both safe and effective for cancer pain. So far, treatments with gabapentin and ketamine have not shown any serious safety issues. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Gabapentin and Ketamine for head and neck cancer pain management because it offers a novel approach compared to standard treatments like opioids and NSAIDs. Gabapentin is known for treating nerve pain, while Ketamine is recognized for its rapid-acting pain relief and potential to reduce opioid use. This combination targets pain pathways differently, potentially providing more effective relief with fewer side effects than traditional options.

What evidence suggests that gabapentin and ketamine might be an effective treatment for head and neck cancer pain?

Studies have shown that gabapentin can reduce the need for opioids in patients with head and neck cancer, suggesting its effectiveness in managing pain. Research indicates that combining gabapentin with ketamine can improve pain control without significantly increasing doses, thereby minimizing side effects. In this trial, participants will receive the gabapentin-ketamine combination to determine its effectiveness in preventing and reducing pain in cancer patients, particularly those undergoing chemoradiation. Overall, this combination is under study for its potential to enhance pain management and safety for cancer patients. ^{1 2 3 4 5}

Who Is on the Research Team?

Natalie Lockney, MD

Principal Investigator

Vanderbilt-Ingram Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 21 with advanced but non-metastatic head and neck cancer, who are about to undergo or are currently receiving radiation or chemoradiation. Participants must be able to consent and speak English. Those already on gabapentin or ketamine, with a history of seizures, schizophrenia, high brain pressure, or poor kidney function cannot join.

Inclusion Criteria

I am 21 years old or older.

My cancer is in the head or neck area, confirmed by a biopsy.

My cancer is advanced but hasn't spread to distant parts of my body.

Exclusion Criteria

I am currently taking gabapentin or ketamine.

I have had issues with high pressure inside my skull.

You have been diagnosed with schizophrenia in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive gabapentin and ketamine three times per day during chemoradiation

28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants are assessed for pain, symptom burden, functionality, and quality of life

Up to 30 days post-treatment

What Are the Treatments Tested in This Trial?

Interventions

• Gabapentin
• Ketamine

Trial Overview The study is testing the safety and appropriate dose of gabapentin combined with ketamine given before treatment to prevent acute and chronic pain in patients undergoing chemoradiation for head and neck cancer.

How Is the Trial Designed?

Group I: Gabapentin plus Ketamine Experimental Treatment 2 Interventions

Gabapentin and Ketamine will be taken 3 times per day.

Gabapentin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Neurontin for:

• Postherpetic neuralgia
• Partial-onset seizures

Approved in European Union as Gabapentin for:

• Peripheral neuropathic pain
• Partial-onset seizures

Approved in Canada as Gabapentin for:

• Postherpetic neuralgia
• Partial-onset seizures

Who Is Running the Clinical Trial?

Dianne Lou

Lead Sponsor

Trials

1

Recruited

60+

Natalie Lockney

Lead Sponsor

Trials

1

Recruited

60+

Published Research Related to This Trial

In a study of 185 head and neck cancer patients, those treated with prophylactic gabapentin showed a significant reduction in opioid use at 3 months, with only 39.6% using opioids compared to 58.3% in the non-gabapentin group.

Gabapentin was found to be independently associated with lower opioid use, suggesting it can help patients taper off opioids more effectively, especially in those not reliant on gastrostomy tubes or using opioids before treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of gabapentin in reducing opioid requirements after radiation in head and neck cancer in a single institution. Gilley, DR., Clark, AD., Wieser, ME., et al.[2022]

A systematic review identified 10 studies on medications for neuropathic pain in head and neck cancer patients undergoing radiotherapy, highlighting the effectiveness of pregabalin, methadone, ketamine, and gabapentin in reducing pain compared to placebo or standard treatments.

Despite the availability of various pharmacological options, there is a significant lack of research specifically targeting neuropathic pain management in head and neck cancer patients, indicating a need for more studies to develop tailored treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological Management of Neuropathic Pain after Radiotherapy in Head and Neck Cancer Patients: A Systematic Review. Kouri, M., Rekatsina, M., Vadalouca, A., et al.[2023]

A new lozenge formulation of ketamine, containing 25 mg, demonstrated good chemical stability for at least 14 weeks, making it a viable option for pain management.

The bioavailability of the lozenge was found to be 24% for both oral and sublingual administration, indicating it could effectively deliver ketamine for treating chronic neuropathic pain, although further efficacy studies are needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a sublingual/oral formulation of ketamine for use in neuropathic pain: Preliminary findings from a three-way randomized, crossover study. Chong, C., Schug, SA., Page-Sharp, M., et al.[2021]

This phase II trial aims to evaluate the efficacy of ketamine mouthwash in reducing pain and opioid use in patients with head and neck cancer undergoing radiation therapy, specifically after the onset of grade 3 mucositis.

The study will enroll 23 participants in the first stage, with the potential to expand to 33 if initial results meet statistical criteria, focusing on pain response and secondary outcomes like dysphagia and sleep quality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of ketamine mouthwash in the management of oral and pharyngeal toxicity associated with head and neck chemoradiotherapy: protocol for a phase II, Simon's two-stage trial. Koffler, D., Eckstein, J., Herman, J., et al.[2023]

Topical gabapentin (6%) significantly reduced pruritus scores in patients with chronic kidney disease-associated pruritus after 2 weeks of treatment, demonstrating its efficacy in managing this condition.

The study, involving 30 patients on hemodialysis, reported no drug-related adverse events, indicating a good safety profile for short-term use of topical gabapentin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled study of 6% gabapentin topical formulation for chronic kidney disease-associated pruritus. Aquino, TMO., Luchangco, KAC., Sanchez, EV., et al.[2021]

A recent randomized controlled trial found that subcutaneous ketamine does not provide a clinical benefit over placebo for managing cancer pain that does not respond to other treatments, leading to significant changes in clinical practice among Australasian clinicians.

Following the trial, 65% of surveyed clinicians altered their prescribing habits for ketamine, with many prescribing it less frequently or only in specific situations, reflecting a shift in practice based on the trial's findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implementing practice change in chronic cancer pain management: clinician response to a phase III study of ketamine. Hardy, JR., Spruyt, O., Quinn, SJ., et al.[2015]

In a study of 417 cervical carcinoma patients with mild to moderate depression, high-dose S-ketamine (0.5 mg/kg) significantly reduced pain and depression scores compared to control and other treatment groups at 1 and 3 days post-surgery.

Both low-dose (0.25 mg/kg) and high-dose S-ketamine improved short-term outcomes better than racemic ketamine, with increased serum levels of BDNF and 5-HT, indicating a potential mechanism for its efficacy in managing depression and pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Various Doses of S-Ketamine in Treatment of Depression and Pain in Cervical Carcinoma Patients with Mild/Moderate Depression After Laparoscopic Total Hysterectomy. Wang, J., Wang, Y., Xu, X., et al.[2021]

Oral ketamine has shown potential as a treatment for neuropathic and cancer pain in palliative care, but the evidence is limited and mixed, primarily from small studies and anecdotal reports.

A case report highlighted the effectiveness of oral ketamine in a patient with chronic pain resistant to other therapies, suggesting it may be beneficial for patients in palliative care, even without prior intravenous trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral ketamine in the palliative care setting: a review of the literature and case report of a patient with neurofibromatosis type 1 and glomus tumor-associated complex regional pain syndrome. Soto, E., Stewart, DR., Mannes, AJ., et al.[2021]

Gabapentin is generally considered safe and non-toxic, but this case report highlights a potential risk of neurologic toxicity in a 75-year-old man with renal dysfunction due to drug accumulation.

The findings suggest that further studies are needed to investigate the neurologic adverse effects of gabapentin, particularly in patients with renal issues, to better understand the risks associated with its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gabapentin-induced neurologic toxicities. Bookwalter, T., Gitlin, M.[2018]

Gabapentin (GBP) is generally considered safe with a low incidence of serious adverse effects, even in cases of intentional overdose, but this case report highlights a rare instance of fatality associated with acute GBP ingestion.

A 47-year-old woman was found dead with a significant concentration of GBP in her system, suggesting that while GBP is usually safe, there can be severe outcomes in isolated cases of overdose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An acute gabapentin fatality: a case report with postmortem concentrations. Cantrell, FL., Mena, O., Gary, RD., et al.[2022]

Ketamine, when applied topically or through localized injections, can provide analgesia for chronic pain, particularly by blocking N-methyl-D-aspartate receptors, although controlled trials have not consistently confirmed its effectiveness for neuropathic pain.

While some case reports suggest that combining topical ketamine with other agents can lead to significant pain relief (40% to 75% response rates), the optimal dosing and combinations remain unclear, indicating a need for further research to identify the best treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical and peripheral ketamine as an analgesic. Sawynok, J.[2021]

A focus group study involving 33 individuals misusing gabapentin revealed that many had been prescribed the drug for legitimate medical reasons over 10 years ago, but now use it recreationally, often in combination with other substances like opioids and cocaine.

Participants reported that gabapentin is low-cost and increasingly popular for its central nervous system effects, indicating a significant potential for abuse that healthcare providers should recognize, suggesting a need to reconsider its regulatory status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A qualitative analysis of gabapentin misuse and diversion among people who use drugs in Appalachian Kentucky. Vickers Smith, R., Boland, EM., Young, AM., et al.[2021]

Gabapentin toxicity can lead to new motor symptoms such as myokymia, as demonstrated in a case study of a 69-year-old man who experienced muscle spasms and tremors after taking a high daily dose of 9600 mg.

A temporary discontinuation of gabapentin (a 'gabapentin holiday') effectively resolved the myokymia and other motor symptoms, highlighting the importance of recognizing this adverse effect for timely diagnosis and treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gabapentin-Induced Myokymia: A Case Report. Brown, A., Esechie, A., Gogia, B., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05156060

Study Details | NCT05156060 | Gabapentin & Ketamine for ... This is a study to establish a safe and feasible dose for prophylactic use of a combination of gabapentin and ketamine in head and neck cancer patients ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.12123

Phase I/II trial of gabapentin plus intranasal ketamine for ... In combination with other analgesics, ketamine may enhance acute and chronic pain control at lower doses thus avoiding dose-limited toxicities.

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-12386

Gabapentin plus Ketamine for the Prevention of Acute and ... This will be the basis for a future, larger study to look at how effective this combination is at reducing and/or preventing pain in head and neck cancer ...

4. withpower.com withpower.com/trial/phase-2-head-and-neck-neoplasms-2022-ee174

Gabapentin + Ketamine for Head and Neck Cancer Pain ... Gabapentin has been shown to reduce opioid use in head and neck cancer patients, indicating its potential effectiveness in managing pain. Additionally, ketamine ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT449220

Phase I/II trial of gabapentin plus intranasal ketamine ... Phase I/II trial of gabapentin plus intranasal ketamine for the prevention and treatment of pain in patients undergoing radiotherapy for head and neck cancer.