A Phase 2 randomized study to assess the radioprotective effect of oral chlorophyllin in acute toxicity reduction for Head Neck cancer patients receiving radiation / chemoradiation.

Head and Neck cancers are one of the commonest cancers in India. Radiation Therapy (RT) either alone or in combination with chemotherapy (chemoradiotherapy-CTRT) is one of the common treatments of head and neck cancers with around 60-80% of patients in India. While RT/ CTRT remains a very effective treatment for head and neck cancers, there are some side effects associated with them including - skin peeling, skin discoloration, mouth ulcers, eating/ swallowing difficulty, dryness of mouth, fever and reduced blood counts. These side effects cause significant deterioration in quality of life of head and neck cancer patients. Recently a study from BARC has demonstrated the benefit of using chlorophyllin (CHL) tablets as an agent which can reduce the side effects associated with RT/ CTRT in certain cancers. This drug is well tolerated and has minimal side effects in the previous studies conducted. However, till date there is no data about the benefit of CHL in head and neck cancers In this study, patients with head and neck cancers will be randomly given Chlorophyllin tablets or a placebo (a placebo is an inactive substance that looks like the drug or treatment being tested) when they are receiving RT/ CTRT. Our primary aim is to assess if CHL can reduce the toxicity of radiotherapy/ chemoradiotherapy in head and neck cancers.

**OBJECTIVES OF THE STUDY:**To assess the efficacy and safety of oral CHL in reducing the acute side effects of RT/ CTRT in HNSCC

It is Phase II Prospective Randomized Placebo controlled trial.

METHODS & INTERVENTIONS

All patients will be discussed in a multidisciplinary tumor board before initiation of RT. The indications of addition of concurrent chemotherapy will be as per standard institutional and national guidelines

In the intervention arm, in addition to the routine standard of care patients will be started on CHL 750 mg OD (provided by IDRS lab, Bengaluru) 7 days prior to the planned RT start date (morning empty stomach). During the course of RT patients will take CHL 750 mg OD 1 hour prior to planned RT delivery (at least 4 hours empty stomach) every day. After the completion of RT patients will take CHL 750 mg OD once daily in the morning (empty stomach) for 7 days.

The compliance to CHL will be ensured by the nursing coordinator assigned to the trial. For patients who undergo a feeding tube insertion during RT, CHL will be given after crushing in water via the nasogastric tube. CHL will be stopped in patients who have any severe side effects likely due to CHL.

Patients in the standard arm will receive a placebo tablet in a similar schedule as CHL. This placebo will be matched in physical properties to CHL and is biologically inert.

The placebo will be provided by IDRS lab, Bengaluru.

The acute toxicity (primary endpoint) will be assessed at any time during the course of RT to 3 months post completion of RT. The primary hypothesis of the study is that CHL will decrease the proportion of patients with grade 3+ acute toxicity (dermatitis, mucositis, dysphagia and xerostomia) from 40% in the standard arm to 25% in the CHL arm. This corresponds to an effect size of 0.33. For an alpha=0.1 and Beta=80%, this corresponds to 100 patients in each arm accrued over 2.5 years (One sided Fisher’s exact test). Assuming a 10% attrition rate the total sample size of the study is n=220 (110 in each arm). The expected duration of trial will be 24 months.

QOL analysis will be conducted using the following tools (with appropriate language translations)

â— EORTC QLQ-30

◠EORTC QLQ – H&N43

QOL analysis will be conducted at every patient visit & Follow Up visits as well.