Efficacy of Ketamine Mouthwash in the Management of Oral and Pharyngeal Toxicity Associated With Head and Neck Chemoradiotherapy: A Phase 2, Simon 2-stage Trial

NCT05331131 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 22-0292
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with head and neck cancer generally receive a standard of care of 7 weeks of daily radiation therapy given alongside an aggressive chemotherapy drug called cisplatin. While rates of cure are often strong for patients who are able to complete treatment without any unscheduled breaks, the rates of high grade toxicity associated with this treatment are high even with the use of the most modern techniques of treatment. Pain, swallowing dysfunction, loss of taste sensation, and ulceration of the mouth and throat are ubiquitous and often contribute to a nutritional breakdown requiring feeding tube placement. Unfortunately, even with aggressive use of opioids and other conventional palliation methods, breakthrough pain and other toxicities are very common. In addition to the quality of life burdens of these side effects, patients who are unable to complete treatment on schedule have worse control of their cancer and worse overall survival. Clearly, there is a clinical need for better management of these toxicities. The investigators hypothesize that ketamine mouthwash may effectively reduce both pain and the need for opioid drugs in this patient population. There is a large body of literature supporting the use of ketamine for pain control in diseases other than cancer, and a smaller but growing body of literature showing the effectiveness of ketamine for control of cancer-associated pain. Additionally, by providing ketamine in mouthwash form, the evidence shows that one can avoid the side effects associated with giving ketamine throughout the body, and in fact no significant side effects have been reported so far with this treatment. In this study, the investigators will provide ketamine mouthwash to patients undergoing the standard treatment for this disease over a two week period, and measure their response in terms of both pain and need for opioids, as well as other measurements of quality of life. The investigators will also measure unscheduled interruptions in treatment. In years to come, the data from this study may show an impact on cancer control and survival.

Conditions

Cancer of Head and Neck; Mucositis Oral; Pharyngeal Mucositis

Keywords

Cancer of Head and Neck; Radiation Therapy; Intensity-Modulated Radiation Therapy; Concurrent chemotherapy; Ketamine; Ketamine mouthwash; Oral mucositis; Pharyngeal mucositis

Outcome Measures

Primary Outcomes (1)

• Assessing Pain Response

  Pain response, defined by international consensus criteria as a combination of pain score per visual analogue scale (0-10) and opioid analgesic use (morphine-equivalent dose), through which the combination of the two measures are unified into a single evaluation of complete response (CR), partial response (PR), indeterminate response (IR), or pain progression (PP), depending upon the dynamics of VAS and MED taken separately

  14 days

Secondary Outcomes (8)

• Assessing Patient-reported pain score

  Daily for 14 days

• Measuring opioid analgesic burden

  Daily for 14 days

• Assessing Sleep Quality

  Nightly for 14 days

• Assessing Dysphagia

  Baseline and repeated at 14 days

• Evaluating the placement of a feeding tube

  Categorical (yes/no) measurement at any time after start of ketamine therapy and prior to completion of cancer-directed therapy, a maximum 14 day period

Study Arms (1)

Ketamine Mouthwash

EXPERIMENTAL

Enrolled patients with histologically confirmed squamous cell carcinoma of the head and neck undergoing definitive radiation therapy to 70Gy with concurrent cisplatin chemotherapy who develop grade 3+ toxicity will be prescribed ketamine mouthwash at a strength of 20mg/5mL in NovaFilm suspension with OraSweet flavoring agent via "swish and spit" route of administration. They will take the investigational drug four times daily.

Drug: Ketamine Topical

Interventions

Ketamine Topical DRUG

Ketamine hydrochloride in mouthwash form

Also known as: Ketamine mouthwash

Ketamine Mouthwash

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged 18-70
• Pathologically proven squamous cell carcinoma of the oral cavity, oropharynx, nasopharynx, larynx, or hypopharynx, with the exception of stages I-II glottic cancer
• Prescribed a curative regimen of definitive radiotherapy to with concurrent cisplatin-based chemotherapy, administered in standard fractionated doses to 70 Gy in 35 Fx
• CTCAE v 5.0 grade 3 or greater oral cavity or pharyngeal mucositis documented to have developed subsequent to initiation of radiation therapy, defined as severe pain limiting oral intake, with at least 14 remaining days on treatment with radiation therapy

You may not qualify if:

• Unable to render informed consent
• Prior history of radiation therapy
• Any other malignancy diagnosed or treated within 10 years prior to enrollment
• Feeding tube placement or tracheostomy prior to initiation of radiation therapy
• Deemed by attending radiation oncologist to be unlikely to adhere to the QID study intervention and daily outcomes reporting as described below
• Any of the following contraindications for ketamine use: high risk for complications due to blood pressure elevation, documented hypersensitivity to ketamine, history of illicit drug use disorder, history of psychotic disorder, or any other medical contraindication attested to by the attending radiation oncologist
• Pregnant or breastfeeding at the time of screening visit

Sponsors & Collaborators

• Northwell Health: lead

Study Sites (1)

Center for Advanced Medicine

Lake Success, New York, 11042, United States

Location

Related Publications (1)

• Koffler D, Eckstein J, Herman J, Martins-Welch D, Seetharamu N, Ghaly M, Kohn N, Potters L, Frank D, Sullivan K, Parashar B. 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. BMJ Open. 2023 Apr 11;13(4):e064809. doi: 10.1136/bmjopen-2022-064809.

  PMID: 37041046 DERIVED

MeSH Terms

Conditions

Head and Neck Neoplasms; Stomatitis

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Mouth Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Bhupesh Parashar, MD, DrPH

  Northwell Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Simon 2-stage

Study Record Dates

• First Submitted: March 24, 2022
• First Posted: April 15, 2022
• Study Start: September 19, 2022
• Primary Completion: May 1, 2025
• Study Completion: November 14, 2025
• Last Updated: January 24, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)