Radiation TreatmentHYPORT-HNNCT06536699
Trial Comparing Avg. Global Qual of Lifescore in Hypo Frac. RT vs Conv. Frac. in H&N Cancers
A study testing Radiotherapy - hypofractionated and Radiotherapy - Conventional in people with Radiation Treatment, run by Tata Medical Center at 1 site in India.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Radiation Treatment
- What is being tested?
- Radiotherapy - hypofractionated and Radiotherapy - Conventional
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 600 participants
- Where
- 1 siteIndia
- Study dates
- 7 Aug 2024to 1 Jul 2031
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- ECOG performance status 0 - 2.
- 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.
- Patients who are being treated with curative intent treatment either with surgery followed by adjuvant radiotherapy with or without chemotherapy or definitive chemoradiation.
- 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.
- Patients with non metastatic cancer, optimally staged with the following:
- Contrast enhanced CT scan of the neck and thorax for cancer lip, oral cavity, oropharynx, hypopharynx, supraglottis, glottis and subglottis
- Magnetic Resonance Imaging of the neck and CT thorax for cancer of nasopharynx
Who cannot join
- 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
- Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
India1 site
Tata Medical Center
Kolkata, West Bengal, 700160
Sanjoy Chatterjee, MRCP,FRCR, 9038161825, sanjoy.chatterjee@tmckolkata.com
Indranil Mallick, MD, DNB
About this study
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
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.
Read more
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
Read the 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
- 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.
- 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.
- Better patient compliance Reduced treatment time will increase patient compliance especially for patients who are taking treatment away from home.
- Conditions
- Radiation Treatment
- Being tested
- Radiotherapy - hypofractionated, Radiotherapy - Conventional
- Keywords
- Hypofractionated radiotherapy, Head and Neck cancer
- Medical subject headings
- Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Radiotherapy - hypofractionatedRadiation
Hypofractionated Radiotherapy of 55 Gy in 20 fractions in definitive setting and 52.5 Gy in 20 fractions in adjuvant setting. Total duration - 4 Weeks
Radiotherapy - ConventionalRadiation
Conventional Radiotherapy of 66 Gy in 30 fractions in definitive setting and 60 Gy in 30 fractions in adjuvant setting. Total duration - 6 Weeks
| Study group | Role | What they receive |
|---|---|---|
| Radiotherapy - conventional | Active comparator | Conventional Radiotherapy of 66 Gy in 30 fractions in definitive setting and 60 Gy in 30 fractions in adjuvant setting Total Duration- 6 weeks Receives: Radiation: Radiotherapy - Conventional |
| Radiotherapy - hypofractionated | Experimental | Hypofractionated Radiotherapy of 55 Gy in 20 fractions in definitive setting and 52.5 Gy in 20 fractions in adjuvant setting. Total duration - 4 Weeks Receives: Radiation: Radiotherapy - hypofractionated |
What is being measured
The primary outcome is the main question the study is designed to answer.
To compare the average global quality of life score following hypofractionated radiotherapy versus conventional fractionation in head and neck cancer
Patients reported outcomes in the form of EORTC QLQ C30 questionnaire at regular designated intervals using electronic patient reported outcome monitoring systems (e-PROMS).
EORTC QLQ C30 stands for European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire C30.
The score will range from 0 to 100 as per the Scoring of the EORTC QLQ-C30 version 3.0.
A higher score will denote a better quality of life.
Measured: 2 Years
Secondary outcomes (2)
To compare the locoregional control at 2 years between the hypofractionated and conventional arm.
To get a Radiological assessment done 3 months post treatment and then followup the patient clinically and only get a radiological correlation if suggested clinically.
Measured: 2 Years
To compare acute and late toxicities of hypofractionated radiotherapy with conventional fractionation
To compare physician reported and patient reported acute toxicities like mucositis, dermatitis and dysphagia between the two groups using weekly assessment of acute toxicities using the RTOG and CTCAE v5 criteria during radiation.
Measured: 2 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2024
- Study start7 Aug 2024 (estimated)
- Primary completion1 Jul 2029 (estimated)
- Study completion1 Jul 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (37)Papers the sponsor has linked to this study.
- Other trials for Radiation TreatmentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Comparison of a shorter course of radiotherapy in 4 weeks with standard treatment of 6 weeks for head and neck cancers
- Masking
- None (open label)
- Enrolment
- 600 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tata Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sanjoy Sanjoy, MRCP,FRCR, Principal investigator, Tata Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06536699
- Sponsor's protocol ID
- 2024/TMC/307/IRB11
- Acronym
- HYPORT-HN
- Status last verified
- Aug 2024
- First submitted
- 1 Jul 2024
- Last updated
- 5 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices).
Publications
Baujat B, Bourhis J, Blanchard P, Overgaard J, Ang KK, Saunders M, Le Maitre A, Bernier J, Horiot JC, Maillard E, Pajak TF, Poulsen MG, Bourredjem A, O'Sullivan B, Dobrowsky W, Andrzej H, Skladowski K, Hay JH, Pinto LH, Fu KK, Fallai C, Sylvester R, Pignon JP; MARCH Collaborative Group. Hyperfractionated or accelerated radiotherapy for head and neck cancer. Cochrane Database Syst Rev. 2010 Dec 8;2010(12):CD002026. doi: 10.1002/14651858.CD002026.pub2.
PubMed 21154350Bentzen SM, Gupta T, Jacinto AA, Rosenblatt E, Bhasker S, Napoles M, Binia S, Chansilpa Y, Aguiar S, Nagarajan M, Laskar SG, De Marchi P, Goloubeva O, Hopkins K, Zubizarreta E, Agarwal JP, Abdel-Wahab M. Hypofractionated Versus Normofractionated Accelerated Radiation Therapy With or Without Cisplatin for Locally Advanced Head and Neck Squamous Cell Carcinoma (HYPNO): A Randomized, Open-Label, Phase 3, Noninferiority Trial. Int J Radiat Oncol Biol Phys. 2026 Jun 1;125(2):387-398. doi: 10.1016/j.ijrobp.2025.12.056. Epub 2026 Feb 19.
PubMed 41711624Fu KK, Pajak TF, Trotti A, Jones CU, Spencer SA, Phillips TL, Garden AS, Ridge JA, Cooper JS, Ang KK. A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: first report of RTOG 9003. Int J Radiat Oncol Biol Phys. 2000 Aug 1;48(1):7-16. doi: 10.1016/s0360-3016(00)00663-5.
PubMed 10924966Thomson DJ, Palma D, Guckenberger M, Balermpas P, Beitler JJ, Blanchard P, Brizel D, Budach W, Caudell J, Corry J, Corvo R, Evans M, Garden AS, Giralt J, Gregoire V, Harari PM, Harrington K, Hitchcock YJ, Johansen J, Kaanders J, Koyfman S, Langendijk JA, Le QT, Lee N, Margalit D, Mierzwa M, Porceddu S, Soong YL, Sun Y, Thariat J, Waldron J, Yom SS. Practice recommendations for risk-adapted head and neck cancer radiotherapy during the COVID-19 pandemic: An ASTRO-ESTRO consensus statement. Radiother Oncol. 2020 Oct;151:314-321. doi: 10.1016/j.radonc.2020.04.019. Epub 2020 Jul 27.
PubMed 32730830Gupta T, Ghosh-Laskar S, Agarwal JP. Resource-sparing curative-intent hypofractionated-accelerated radiotherapy in head and neck cancer: More relevant than ever before in the COVID era. Oral Oncol. 2020 Dec;111:105045. doi: 10.1016/j.oraloncology.2020.105045. Epub 2020 Oct 20.
PubMed 33091846Adelstein DJ, Li Y, Adams GL, Wagner H Jr, Kish JA, Ensley JF, Schuller DE, Forastiere AA. An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. J Clin Oncol. 2003 Jan 1;21(1):92-8. doi: 10.1200/JCO.2003.01.008.
PubMed 12506176Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, Glisson B, Trotti A, Ridge JA, Chao C, Peters G, Lee DJ, Leaf A, Ensley J, Cooper J. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003 Nov 27;349(22):2091-8. doi: 10.1056/NEJMoa031317.
PubMed 14645636Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, Kish JA, Kim HE, Cmelak AJ, Rotman M, Machtay M, Ensley JF, Chao KS, Schultz CJ, Lee N, Fu KK; Radiation Therapy Oncology Group 9501/Intergroup. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med. 2004 May 6;350(19):1937-44. doi: 10.1056/NEJMoa032646.
PubMed 15128893Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefebvre JL, Greiner RH, Giralt J, Maingon P, Rolland F, Bolla M, Cognetti F, Bourhis J, Kirkpatrick A, van Glabbeke M; European Organization for Research and Treatment of Cancer Trial 22931. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med. 2004 May 6;350(19):1945-52. doi: 10.1056/NEJMoa032641.
PubMed 15128894Lacas B, Carmel A, Landais C, Wong SJ, Licitra L, Tobias JS, Burtness B, Ghi MG, Cohen EEW, Grau C, Wolf G, Hitt R, Corvo R, Budach V, Kumar S, Laskar SG, Mazeron JJ, Zhong LP, Dobrowsky W, Ghadjar P, Fallai C, Zakotnik B, Sharma A, Bensadoun RJ, Ruo Redda MG, Racadot S, Fountzilas G, Brizel D, Rovea P, Argiris A, Nagy ZT, Lee JW, Fortpied C, Harris J, Bourhis J, Auperin A, Blanchard P, Pignon JP; MACH-NC Collaborative Group. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group. Radiother Oncol. 2021 Mar;156:281-293. doi: 10.1016/j.radonc.2021.01.013. Epub 2021 Jan 27.
PubMed 33515668Haselow RE, Warshaw MG, Oken MM, et al. Radiation alone versus radiation with weekly low dose cis-platinum in unresectable cancer of the head and neck. In: Fee WE Jr, Goepfert H, Johns ME, et al, editors. Head and Neck Cancer, vol. II. Toronto, Canada and Philadelphia, PA: BC Decker; 1990. pp 279-281.
Quon H, Leong T, Haselow R, Leipzig B, Cooper J, Forastiere A. Phase III study of radiation therapy with or without cis-platinum in patients with unresectable squamous or undifferentiated carcinoma of the head and neck: an intergroup trial of the Eastern Cooperative Oncology Group (E2382). Int J Radiat Oncol Biol Phys. 2011 Nov 1;81(3):719-25. doi: 10.1016/j.ijrobp.2010.06.038. Epub 2010 Oct 1.
PubMed 20888709Jeremic B, Shibamoto Y, Stanisavljevic B, Milojevic L, Milicic B, Nikolic N. Radiation therapy alone or with concurrent low-dose daily either cisplatin or carboplatin in locally advanced unresectable squamous cell carcinoma of the head and neck: a prospective randomized trial. Radiother Oncol. 1997 Apr;43(1):29-37. doi: 10.1016/s0167-8140(97)00048-0.
PubMed 9165134Jeremic B, Milicic B, Dagovic A, Vaskovic Z, Tadic L. Radiation therapy with or without concurrent low-dose daily chemotherapy in locally advanced, nonmetastatic squamous cell carcinoma of the head and neck. J Clin Oncol. 2004 Sep 1;22(17):3540-8. doi: 10.1200/JCO.2004.10.076.
PubMed 15337803Jeremic B, Shibamoto Y, Milicic B, Nikolic N, Dagovic A, Aleksandrovic J, Vaskovic Z, Tadic L. Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplatin in locally advanced squamous cell carcinoma of the head and neck: a prospective randomized trial. J Clin Oncol. 2000 Apr;18(7):1458-64. doi: 10.1200/JCO.2000.18.7.1458.
PubMed 10735893
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06536699
- Acronym / sponsor ID
- HYPORT-HN / 2024/TMC/307/IRB11
- Conditions
- Radiation Treatment
- Keywords
- Hypofractionated radiotherapy, Head and Neck cancer
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 600 participants (estimated)
- Lead sponsor
- Tata Medical CenterUniversity, hospital or other
- Study start
- 7 Aug 2024 (estimated)
- Primary completion
- 1 Jul 2029 (estimated)
- Study completion
- 1 Jul 2031 (estimated)
- First posted
- 5 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- 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.
- 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.
- Better patient compliance Reduced treatment time will increase patient compliance especially for patients who are taking treatment away from home.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Comparison of a shorter course of radiotherapy in 4 weeks with standard treatment of 6 weeks for head and neck cancers
| Arm | Type | Receives |
|---|---|---|
| Radiotherapy - conventional | Active comparator | Radiation: Radiotherapy - ConventionalConventional Radiotherapy of 66 Gy in 30 fractions in definitive setting and 60 Gy in 30 fractions in adjuvant setting Total Duration- 6 weeks |
| Radiotherapy - hypofractionated | Experimental | Radiation: Radiotherapy - hypofractionatedHypofractionated Radiotherapy of 55 Gy in 20 fractions in definitive setting and 52.5 Gy in 20 fractions in adjuvant setting. Total duration - 4 Weeks |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age ≥ 18 years
- ECOG performance status 0 - 2.
- 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.
- Patients who are being treated with curative intent treatment either with surgery followed by adjuvant radiotherapy with or without chemotherapy or definitive chemoradiation.
- 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.
Key exclusion criteria (2 listed)
- 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
- Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Radiotherapy - hypofractionatedHypofractionated Radiotherapy of 55 Gy in 20 fractions in definitive setting and 52.5 Gy in 20 fractions in adjuvant setting. Total duration - 4 Weeks | Radiation | Radiotherapy - hypofractionated |
| Radiotherapy - ConventionalConventional Radiotherapy of 66 Gy in 30 fractions in definitive setting and 60 Gy in 30 fractions in adjuvant setting. Total duration - 6 Weeks | Radiation | Radiotherapy - conventional |
Primary outcome
To compare the average global quality of life score following hypofractionated radiotherapy versus conventional fractionation in head and neck cancer
Time frame: 2 Years
Patients reported outcomes in the form of EORTC QLQ C30 questionnaire at regular designated intervals using electronic patient reported outcome monitoring systems (e-PROMS). EORTC QLQ C30 stands for European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire C30. The score will range from 0 to 100 as per the Scoring of the EORTC QLQ-C30 version 3.0. A higher score will denote a better quality of life.
2 secondary outcomes
To compare the locoregional control at 2 years between the hypofractionated and conventional arm.
Time frame: 2 Years
To compare acute and late toxicities of hypofractionated radiotherapy with conventional fractionation
Time frame: 2 Years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2024.
- Background: PubMed 21154350Baujat B, Bourhis J, Blanchard P, Overgaard J, Ang KK, Saunders M, Le Maitre A, Bernier J, Horiot JC, Maillard E, Pajak TF, Poulsen MG, Bourredjem A, O'Sullivan B, Dobrowsky W, Andrzej H, Skladowski K, Hay JH, Pinto LH, Fu KK, Fallai C, Sylvester R, Pignon JP; MARCH Collaborative Group. Hyperfractionated or accelerated radiotherapy for head and neck cancer. Cochrane Database Syst Rev. 2010 Dec 8;2010(12):CD002026. doi: 10.1002/14651858.CD002026.pub2.
- Background: PubMed 41711624Bentzen SM, Gupta T, Jacinto AA, Rosenblatt E, Bhasker S, Napoles M, Binia S, Chansilpa Y, Aguiar S, Nagarajan M, Laskar SG, De Marchi P, Goloubeva O, Hopkins K, Zubizarreta E, Agarwal JP, Abdel-Wahab M. Hypofractionated Versus Normofractionated Accelerated Radiation Therapy With or Without Cisplatin for Locally Advanced Head and Neck Squamous Cell Carcinoma (HYPNO): A Randomized, Open-Label, Phase 3, Noninferiority Trial. Int J Radiat Oncol Biol Phys. 2026 Jun 1;125(2):387-398. doi: 10.1016/j.ijrobp.2025.12.056. Epub 2026 Feb 19.
- Background: PubMed 10924966Fu KK, Pajak TF, Trotti A, Jones CU, Spencer SA, Phillips TL, Garden AS, Ridge JA, Cooper JS, Ang KK. A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: first report of RTOG 9003. Int J Radiat Oncol Biol Phys. 2000 Aug 1;48(1):7-16. doi: 10.1016/s0360-3016(00)00663-5.
- Background: PubMed 32730830Thomson DJ, Palma D, Guckenberger M, Balermpas P, Beitler JJ, Blanchard P, Brizel D, Budach W, Caudell J, Corry J, Corvo R, Evans M, Garden AS, Giralt J, Gregoire V, Harari PM, Harrington K, Hitchcock YJ, Johansen J, Kaanders J, Koyfman S, Langendijk JA, Le QT, Lee N, Margalit D, Mierzwa M, Porceddu S, Soong YL, Sun Y, Thariat J, Waldron J, Yom SS. Practice recommendations for risk-adapted head and neck cancer radiotherapy during the COVID-19 pandemic: An ASTRO-ESTRO consensus statement. Radiother Oncol. 2020 Oct;151:314-321. doi: 10.1016/j.radonc.2020.04.019. Epub 2020 Jul 27.
- Background: PubMed 33091846Gupta T, Ghosh-Laskar S, Agarwal JP. Resource-sparing curative-intent hypofractionated-accelerated radiotherapy in head and neck cancer: More relevant than ever before in the COVID era. Oral Oncol. 2020 Dec;111:105045. doi: 10.1016/j.oraloncology.2020.105045. Epub 2020 Oct 20.
- Background: PubMed 12506176Adelstein DJ, Li Y, Adams GL, Wagner H Jr, Kish JA, Ensley JF, Schuller DE, Forastiere AA. An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. J Clin Oncol. 2003 Jan 1;21(1):92-8. doi: 10.1200/JCO.2003.01.008.
- Background: PubMed 14645636Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, Glisson B, Trotti A, Ridge JA, Chao C, Peters G, Lee DJ, Leaf A, Ensley J, Cooper J. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003 Nov 27;349(22):2091-8. doi: 10.1056/NEJMoa031317.
- Background: PubMed 15128893Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, Kish JA, Kim HE, Cmelak AJ, Rotman M, Machtay M, Ensley JF, Chao KS, Schultz CJ, Lee N, Fu KK; Radiation Therapy Oncology Group 9501/Intergroup. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med. 2004 May 6;350(19):1937-44. doi: 10.1056/NEJMoa032646.
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- Background: PubMed 33515668Lacas B, Carmel A, Landais C, Wong SJ, Licitra L, Tobias JS, Burtness B, Ghi MG, Cohen EEW, Grau C, Wolf G, Hitt R, Corvo R, Budach V, Kumar S, Laskar SG, Mazeron JJ, Zhong LP, Dobrowsky W, Ghadjar P, Fallai C, Zakotnik B, Sharma A, Bensadoun RJ, Ruo Redda MG, Racadot S, Fountzilas G, Brizel D, Rovea P, Argiris A, Nagy ZT, Lee JW, Fortpied C, Harris J, Bourhis J, Auperin A, Blanchard P, Pignon JP; MACH-NC Collaborative Group. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group. Radiother Oncol. 2021 Mar;156:281-293. doi: 10.1016/j.radonc.2021.01.013. Epub 2021 Jan 27.
- BackgroundHaselow RE, Warshaw MG, Oken MM, et al. Radiation alone versus radiation with weekly low dose cis-platinum in unresectable cancer of the head and neck. In: Fee WE Jr, Goepfert H, Johns ME, et al, editors. Head and Neck Cancer, vol. II. Toronto, Canada and Philadelphia, PA: BC Decker; 1990. pp 279-281.
- Background: PubMed 20888709Quon H, Leong T, Haselow R, Leipzig B, Cooper J, Forastiere A. Phase III study of radiation therapy with or without cis-platinum in patients with unresectable squamous or undifferentiated carcinoma of the head and neck: an intergroup trial of the Eastern Cooperative Oncology Group (E2382). Int J Radiat Oncol Biol Phys. 2011 Nov 1;81(3):719-25. doi: 10.1016/j.ijrobp.2010.06.038. Epub 2010 Oct 1.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Sanjoy Sanjoy, MRCP,FRCR principal investigator
Tata Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Radiotherapy - hypofractionated and Radiotherapy - Conventional in people with Radiation Treatment, run by Tata Medical Center at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 5 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sanjoy Sanjoy, MRCP,FRCR (9038161825, sanjoy.chatterjee@tmckolkata.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To compare the average global quality of life score following hypofractionated radiotherapy versus conventional fractionation in head and neck cancer (time frame: 2 Years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06536699, which also lists 37 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2024.