A randomized trial to assess the effect of Oral Cryotherapy in prevention of mucositis in head and neck cancer patients receiving Chemo-Radiotherapy

Rationalefor the study:

Oral mucositis is one of the most commonside effects in cancer treatment. Severe mucositis may lead to non-complianceto treatment and complications that could add substantially to the cost ofcare. Oral cryotherapy is effective for the prevention of oral mucositis inadults receiving chemotherapy for solid cancer patients. But the effect of oralcryotherapy in patient receiving Chemoradiation for the treatment of head andneck cancer is still unknown.

Aim**:**To assess the effect of oral-cryotherapy in preventionof oral-mucositis in head and neck cancer patients receivingChemo-radiotherapy.

Primary Objective**:**

To assess the effect of addition ofprophylactic oral-cryotherpy in prevention of Gr-3 to Gr-4 oral Mucositis inpatients who receive chemo-radiotherapy for Head and Neck cancers.

SecondaryObjective:

To compare the QOL at theend of CTRT between the 2 arms.

To compare the patientcompliance to definitive treatment.

Toassess additional cost incurred for  management of Mucositis in both thearms.

StudyType:

Open label, parallel design, randomizedcontrolled study

Study Methodolgy:

Screening Visit:

Allpatients who are planned for Chemoradiotherapy in Tata Memorial Centre will bescreened for the study. If the inclusion/Exclusion criteria are fulfilled thepatient will be enrolled after well informed written consent and randomized.

Randomization:

Patientswill be randomly assigned to  either of the 2 arms in 1:1 ratio by stratified randomization method where stratum would consistof platinum based chemotherapy, taxane based chemotherapy and others.

Study Intervention:

Arm A- Interventionarm(Definitive CT-RT + Oral-cryotherapy)

Arm B- Controlarm(Definitive CT-RT)

Arm A**:** All patientsrandomized to Arm-A will be given oral-cryotherapy in the form of ice cubes/ice-chips/icedwater within 5 fractions of start of Radio-therapy till the end of Radiotherapyor occurrence of Gr-3 or more mucositis whichever is earlier.

Arm B**:** Patients will begiven Chemo-radiotherapy as per the treatment plan.

Chemoradiation in both arms will be in accordance with theinstitutional standards and standard guidelines like NCCN, ESMO.

Patients may be advised sodium bicarbonate gargles as per thetreating physician.

Cryotherapy administration**:**

Patient has to take oral-cryotherapy 5-7 times a day by theprocedure as specified.

Patientswill be provided with ice cubes/crushed ice or ice pop 30 min prior to thestart of radiotherapy. Once the ice melts, the liquid is rinsed around themouth to cool as large surface as possible of the oral mucosa. In addition, toachieve cooling of the hindmost part of the throat, the liquid is gurgled for afew seconds before it is swallowed or spat out. The procedure is repeated for20-30minutes until start of radiotherapy and 10 minutes after the terminationof the Radiotherapy dose for the day. The same will be followed if patient haschemotherapy dose also, except that the patient has to keep cold water in mouthduring chemotherapy. Other than chemo/radio-therapy dose of the day, thepatient has to repeat the same for 5-6 times per day

During treatmentthe patient may if necessary, rest for a maximum of 5 min. Food and drinkshould, whenever possible, be consumed either before or after the coolingsession.

Data Collection at baseline:

All patients will undergo baselineevaluations.

Demographic details will berecorded

Baseline evaluations of height,Weight, BMI

Previous medical history will becollected.

Baseline Oral Mucositis gradingwill be done as per NCI-CTCAE 5.0.

Quality of Life will be measuredusing QLQ-C30 and H&N-35

Study Visits:

The follow-up visits will be asper routine visits for patients under CT-RT.

Patients will undergo laboratoryinvestigations as per their physician’s discretion.

Compliance with trial interventionwill be evaluated.

Oral Mucositis grading will bedone at each visit as per NCI-CTCAE 5.0. Weight loss if any will be recorded ateach visit and graded as per NCI-CTCAE 5.0.

Any other adverse event orConcomitant medications will be recorded at each visit.

Quality of Life will be recordedat baseline and first 3 months follow-up post CTRT

Withdrawal Rules:

The following are reasonsfor removing a patient from the trial:

Any condition that is acontra-indication for oral intake

Definitive treatmentwith-held due to toxicity.

Patient elects todiscontinue his/her participation in the trial by withdrawing consent

Progressive diseaseleading to discontinuation of definitive treatment.

Gr-3 or Gr-4 mucositisthat would require management

PrimaryEnd-point**:**

Occurrence of Gr-3 to Gr-5Mucositis at any time point during CT-RT and post 3 months of its completion

SecondaryEnd-points**:**

To compare the complianceto definitive treatment between two arms

To compare the QOL at theend of CTRT between the 2 arms

To compare the costincurred for management of mucositis between 2 arms

Sample Size Calculation:

Assuminggrade 3 and above mucositis incidence of 67%, to decrease the mucositis by 10%using a type 1 error of 5% and type of 20% , 1:1 allocation , we will require128 patients.