Clinical trial NCT06536699: Trial Comparing Avg. Global Qual of Lifescore in Hypo Frac. RT vs Conv. Frac. in H&N Cancers
Official title: A Randomised Non Inferiority Trial to Compare the Average Global Quality of Life Score Following Hypofractionated Radiotherapy Versus Conventional Fractionation in Head and Neck Cancers
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Radiation Treatment
Keywords: Hypofractionated radiotherapy
Head and Neck cancer
Lead sponsor: Tata Medical Center
Sponsor class: OTHER
First posted: 2024-08-05
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Comparison of a shorter course of radiotherapy in 4 weeks with standard treatment of 6 weeks for head and neck cancers
Primary purpose: TREATMENT

Brief summary: Radiotherapy forms an integral part of Head and Neck cancer treatment in both definitive as well as adjuvant setting. This study explores the use of hypofractionated radiotherapy, delivering 55Gy in 20 fractions over 4 weeks in comparison to the conventional approach which involves 70 Gy over 6 weeks.

Hypofractionated radiotherapy would result in significant benefits in terms of shortening the overall treatment time, countering accelerated hypofraction effects that typically arise after the 4th week. The new approach is also anticipated to offer resource and financial advantages, involving less machine time per patient, and potentially leading to better patient compliance. Previous studies on hypofractionation in Head and Neck cancer have demonstrated good local control and acceptable toxicity levels compared to conventional methods.

The primary objective of this study is to compare the average global quality of life following hypofractionated radiotherapy versus conventional fractionation, with secondary objectives including a comparison of locoregional control at 2 years and assessment of acute and late toxicities.

The study will require 600 eligible patients randomly assigned to either the hypofractionated or conventional arm. For definitive chemoradiation, the control arm will receive 66Gy in 30 fractions over 6 weeks, while the experimental arm will receive 55Gy in 20 fractions over 4 weeks, along with Inj Cisplatin @ 100mg/m2 3 weekly for 2 cycles. In the adjuvant setting control arm will receive 60Gy in 30 fractions over 6 weeks and experimental arm will receive 52.5Gy in 20 fractions over 4 weeks along with Inj Cisplatin @ 100mg /m2 3 weekly for 2 cycles for both arms based on histopathological indications.

Physician reported and patient reported acute toxicities like mucositis, dermatitis and dysphagia, weight loss, requirement and duration of feeding tubes as well as patients reported outcomes in the form of EORTC QLQ C30, HN43 and XeQoLS will be recorded both during and after treatment at regular intervals for 2 years.

The study's duration is five years, aiming to determine whether the hypofractionated schedule is non-inferior to conventional radiotherapy in terms of safety and disease-related outcomes

Detailed description: Head and neck cancers comprise of cancers of arising from the epithelial lining of the lip, oral cavity, pharynx and larynx. The overall incidence of Head and Neck cancers continues to increase, despite decrease in the incidence of smoking suggestive of potential change in etiology. Presently Head and Neck cancer form the seventh most common cancer globally The primary treatment of oral cavity cancer comprises of surgery with adjuvant radiation with or without chemotherapy for locally advanced cancers or early-stage cancer in presence of high-risk factor. Cancers of the oropharynx are treated primarily with radiotherapy for early stage and chemoradiation for locally advanced disease. Laryngeal cancers are treated with either radiotherapy alone or chemoradiation, with surgery reserved for patients with laryngeal cartilage involvement or non-functional larynx.

Radiotherapy for head and neck cancer is delivered with conventional fractionation at 2- 2.2Gy per fraction to a total of 70 Gy dose equivalent. There are certain other altered fractionation types which has been tested like hyperfractionation with an intention to reduce late toxicities as well as accelerated and hypofractionation to counteract the effects of accelerated repopulation. Altered fractionation trials with hyperfractionation show increase in overall survival benefit when compared to radiotherapy alone but worse OS outcomes when compared to chemoradiation with lower toxicities. The advent of the COVID 19 pandemic popularised hypofractionated regimens with the ASTRO-ESTRO consensus statement which achieved a strong consensus about hypofractionated RT.

The addition of concurrent chemotherapy has been found to be superior compared to radiation alone in terms of locoregional control as well as overall survival. The MACH-NC meta analysis showed a 6.5% difference at 5 years and 3.6% at 10 years in favour of concurrent chemotherapy. The optimal dose of chemotherapy remains an important question. Although several studies have shown a significant improvement in overall survival with increasing cumulative cisplatin doses there might not be additional benefit of increasing dose of chemotherapy beyond a cumulative dose of 200mg/m2.

Through this study, the investigators aim to assess and compare the disease related outcomes, acute and late toxicities as well as the quality of life parameters of patients treated with hypofractionated radiotherapy along with two cycles 3 weekly concurrent chemotherapy versus those following the conventional chemotherapy regimen.

Rationale of study

1. Reduction in overall treatment time Squamous cell cancer of the Head and Neck region are rapidly proliferating cancers. Earlier studies have estimated a median value of labeling S-phase fraction (LI), duration, and estimated potential doubling time (Tpot) as 9%, 9 hours, and 5 days respectively. Although some studies failed to show any predictive value of pretreatment potential doubling time and labeling index in patients treated with conventional fractionation the effect of accelerated repopulation which is estimated to be triggered around about 4 +/- 1 weeks cannot be undermined. Several studies have shown a strong negative relation between overall treatment time and locoregional control and overall survival with an average loss of LRC from 1-1.2% per day to 12-14% per week. The dose time factor, also known as the K factor (or λ/α factor as used in some publications) ranges between 0.5 and 0.99 Gy/day with a recent meta-analysis on laryngeal cancers estimating it as 0.6 - 0.8.
2. Resource and financial benefits for patients, caregivers and hospitals. Reduction in total number of fractions will lead to an overall shorter duration of treatment and lesser number of hospital visits. For patients, an earlier end to treatment and lesser number of hospital visits will be a source of physical and financial relief. For caregivers, this will allow an earlier return to work or other responsibilities. For the healthcare system, it allows more patients to be offered treatment using the same resources.
3. Better patient compliance Reduced treatment time will increase patient compliance especially for patients who are taking treatment away from home.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years
2. ECOG performance status 0 - 2.
3. Patients diagnosed with invasive squamous cell cancer of the head and neck region which includes lip, oral cavity, nasopharynx, oropharynx, hypopharynx, supraglottis, glottis and subglottis.
4. Patients who are being treated with curative intent treatment either with surgery followed by adjuvant radiotherapy with or without chemotherapy or definitive chemoradiation.
5. Patients must have a histopathological proof of malignancy, such as biopsy or post operative histopathology report. Biopsies or surgeries done outside must have been reviewed for pathological confirmation and specimen adequacy at the treating institute.
6. Patients with non metastatic cancer, optimally staged with the following:

   1. Contrast enhanced CT scan of the neck and thorax for cancer lip, oral cavity, oropharynx, hypopharynx, supraglottis, glottis and subglottis
   2. Magnetic Resonance Imaging of the neck and CT thorax for cancer of nasopharynx

Exclusion Criteria:

1. Concurrent illness like severe cardiac, renal or hepatic dysfunction and, including severe infection that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety
2. Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol.

Primary outcomes:
measure: To compare the average global quality of life score following hypofractionated radiotherapy versus conventional fractionation in head and neck cancer
timeFrame: 2 Years
Secondary outcomes:
measure: To compare the locoregional control at 2 years between the hypofractionated and conventional arm.
timeFrame: 2 Years
measure: To compare acute and late toxicities of hypofractionated radiotherapy with conventional fractionation
timeFrame: 2 Years
Other outcomes:
Locations:
city: Kolkata
country: India
facility: Tata Medical Center
state: West Bengal
Study officials:
affiliation: Tata Medical Center
name: Sanjoy Sanjoy, MRCP,FRCR
role: PRINCIPAL_INVESTIGATOR
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