| CTRI Number |
CTRI/2023/06/054417 [Registered on: 26/06/2023] Trial Registered Prospectively |
| Last Modified On: |
05/12/2024 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Interventional |
|
Type of Study
|
Radiation Therapy |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
Analyzing the feasibility and benefit of Hippocampus sparing in Head and Neck cancer radiotherapy. |
|
Scientific Title of Study
|
RANDOMISED CONTROLLED TRIAL ANALYSING DOSIMETRY AND NEUROCOGNITIVE OUTCOMES OF HIPPOCAMPAL SPARING RADIOTHERAPY IN HEAD AND NECK CANCERS |
| Trial Acronym |
HipART-HN |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Ashutosh Mukherji |
| Designation |
Professor and Head of the Department |
| Affiliation |
Mahamana Pandit Madanmohan Malaviya Cancer Centre and Homi Bhabha Cancer Hospital, Varanasi |
| Address |
Department of Radiation Oncology,
Mahamana Pandit Madanmohan Malaviya Cancer Centre and Homi Bhabha Cancer Hospital, Near Naria Gate, Sunderpur,
Varanasi
Varanasi
UTTAR PRADESH
221005
India |
| Phone |
9489146747 |
| Fax |
|
| Email |
drashutoshm@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Ashutosh Mukherji |
| Designation |
Professor and Head of the Department |
| Affiliation |
Mahamana Pandit Madanmohan Malaviya Cancer Centre and Homi Bhabha Cancer Hospital, Varanasi |
| Address |
Department of Radiation Oncology,
Mahamana Pandit Madanmohan Malaviya Cancer Centre and Homi Bhabha Cancer Hospital, Near Naria Gate, Sunderpur,
Varanasi
UTTAR PRADESH
221005
India |
| Phone |
9489146747 |
| Fax |
|
| Email |
drashutoshm@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr NARAPAREDDY VENKATA DINESH REDDY |
| Designation |
JUNIOR RESIDENT |
| Affiliation |
Mahamana Pandit Madanmohan Malaviya Cancer Centre and Homi Bhabha Cancer Hospital, Varanasi |
| Address |
Department of Radiation Oncology,
Mahamana Pandit Madanmohan Malaviya Cancer Centre and Homi Bhabha Cancer Hospital, Near Naria Gate, Sunderpur,
Varanasi
Varanasi
UTTAR PRADESH
221005
India |
| Phone |
7981905443 |
| Fax |
|
| Email |
nv35853@gmail.com |
|
|
Source of Monetary or Material Support
|
| Tata Memorial Centre, Varanasi, Uttar Pradesh- 221005 |
|
|
Primary Sponsor
|
| Name |
Dr Ashutosh Mukherji |
| Address |
Professor and Head of Department,
Department of Radiation Oncology, Mahamana Pandit Madanmohan
Malaviya Cancer Centre and Homi Bhabha Cancer Hospital, Near
Naria Gate, Sunderpur, Varanasi
Varanasi
UTTAR PRADESH
221005
India |
| Type of Sponsor |
Other [Self] |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Ashutosh Mukherji |
Mahamana Pandit Madan Mohan Malviya Cancer Center |
RT Review room, Department of Radiation Oncology, Mahamana Pandit Madan Mohan Malviya Cancer Center, Sundar Bagiya, Sundarpur, Varanasi
Varanasi
UTTAR PRADESH |
9489146747
drashutoshm@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| INSTITUTIONAL ETHICS COMMITTEE (IEC) |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C300||Malignant neoplasm of nasal cavity, (2) ICD-10 Condition: C00-C14||Malignant neoplasms of lip, oral cavity and pharynx, (3) ICD-10 Condition: C696||Malignant neoplasm of orbit, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Hippocampal Sparing Radiotherapy |
All patients will be treated with 2-3 planning target volumes [PTV]- High risk and Low-risk PTVs [Intermediate risk PTVs, if needed], among which the high-risk volume will receive a simultaneous integrated boost (SIB). Post-operative patients who need adjuvant RT will be prescribed a dose of 60Gy-66Gy (depending on Margin status) and 54Gy in 30-33 once-daily fractions respectively with IMRT/Rapid ARC. Patients who are planned for definitive RT/ Chemo-RT will be prescribed doses of 66-70Gy and 54-56 Gy in 30-33 once-daily fractions to HR- PTV and LR-PTV respectively with IMRT/Rapid ARC technique. The use of concurrent chemotherapy will be as per standard guidelines. Treatment planning will be done using Eclipse Version 15.1. Inverse optimization to achieve dose constraints for OARs is as per standard guidelines.
In addition to the standard of care planning in the comparator arm,, the Hippocampus will be delineated for all patients in the HS-RT arm according to the criterion of RTOG 0933 using T1 weighted MRI images. Hippocampal avoidance regions will be generated by expanding hippocampal contours by a margin of 5mm. Standard constraints for the hippocampus can be taken from standard constraints of Whole brain RT with D40 7.2Gy, Dmax 16Gy, and D100 9Gy as per RTOG 0933.
The best plan thus generated will be approved by consensus of the PI and co-investigators. Then the approved IMRT/ RapidARC plan will be used to treat the patient in the planned 30-33 fractions as per the appropriate dose prescription. At a planned rate of 5 fractions per week, the total radiotherapy treatment will be delivered in 6 to 7 weeks. |
| Comparator Agent |
Standard IMRT/ Rapid ARC Radiotherapy Planning |
All patients will be treated with 2-3 planning target volumes [PTV]- High risk and Low-risk PTVs [Intermediate risk PTVs, if needed], among which the high-risk volume will receive a simultaneous integrated boost (SIB).
Post-operative patients who need adjuvant RT will be prescribed a dose of 60Gy-66Gy (depending on Margin status) and 54Gy in 30-33 once-daily fractions respectively with IMRT/Rapid ARC. Patients who are planned for definitive RT/ Chemo-RT will be prescribed doses of 66-70Gy and 54-56 Gy in 30-33 once-daily fractions to HR- PTV and LR-PTV respectively with IMRT/Rapid ARC technique.
The use of concurrent chemotherapy will be as per standard guidelines. Treatment planning will be done using Eclipse Version 15.1. Inverse optimization to achieve dose constraints for OARs is as per standard guidelines. The best plan thus generated will be approved by consensus of the PI and co-investigators. Then the approved IMRT/ RapidARC plan will be used to treat the patient in the planned 30-33 fractions as per the appropriate dose prescription. At a planned rate of 5 fractions per week, the total radiotherapy treatment will be delivered in 6 to 7 weeks. |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
75.00 Year(s) |
| Gender |
Both |
| Details |
- Head and neck Squamous or Adeno carcinoma post-operative with PTV involving high masticator space or high infratemporal fossa or nasal cavity or paranasal sinuses planned for adjuvant radiotherapy with or without concurrent chemotherapy with equivalent prescription doses in the range of 60-66 Gy (depending on margin status).
- Cancers of the nasopharynx or nasal cavity or paranasal sinuses or orbit planned for definitive radiotherapy with or without concurrent chemotherapy with equivalent prescription doses above 66-70Gy
- Age: 18-75years
- ECOG: 0-2
- Non-Metastatic disease
- Curative Intent of treatment |
|
| ExclusionCriteria |
| Details |
- Prior Radiotherapy to Head and Neck region/ Brain
- Gross tumor volume in the hippocampal region or within a 5mm margin around the hippocampus
- Previous or present history of neurological diseases or syndromes
- Pregnant or Lactating women
- Blindness
- Contraindications to MR imaging such as Implanted Metal devices or foreign bodies, severe claustrophobia
- Co-existing surgical or medical conditions precluding the use of Radical/Adjuvant RT/CTRT. |
|
|
Method of Generating Random Sequence
|
Stratified block randomization |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Participant Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Dosimetric differences between hippocampal sparing & non-hippocampal sparing radiotherapy in patients of head & neck cancers |
Radiotherapy Planning before Radiotherapy Treatment |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| Neurocognitive function measured by ADDENBROOKE’S COGNITIVE EXAMINATION – ACE-III |
3- & 6-months post radiotherapy follow-up |
| Acute toxicities as per RTOG criteria will be recorded |
During Radiotherapy & 1 & 3 months post radiotherapy treatment |
|
|
Target Sample Size
|
Total Sample Size="56"
Sample Size from India="56"
Final Enrollment numbers achieved (Total)= "56"
Final Enrollment numbers achieved (India)="56" |
|
Phase of Trial
|
Phase 2 |
|
Date of First Enrollment (India)
|
04/07/2023 |
| Date of Study Completion (India) |
Date Missing |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Date Missing |
|
Estimated Duration of Trial
|
Years="1"
Months="6"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Yet Recruiting |
| Recruitment Status of Trial (India) |
Completed |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
Head and Neck cancers are one of the most common cancers in many developing countries like India. The mainstay of treatment for loco-regionally advanced head and neck cancer is either surgery followed by adjuvant radiation therapy or definitive radiotherapy with/ without concurrent chemotherapy. In radiotherapy in head and neck malignancies, the hippocampus has not been conventionally considered as a organ-at risk and has not been delineated and spared. In radiotherapy to the brain in case of CNS malignancies, recent evidence has demonstrated the effectiveness of hippocampal sparing in reducing radiation-related cognitive decline and QoL, using more conformal techniques like Intensity Modulated Radiotherapy [IMRT], Volumetric Modulated Arc Therapy [VMAT], and Proton Therapy. Recent dosimetric studies have established that the hippocampus dose in routine head and neck radiotherapy is often significant and may potentially lead to hippocampal toxicities.
This trial aims to firstly dosimetrically study the hippocampal radiation dose with and without specific hippocampal avoidance techniques in radiotherapy planning without compromising on the target structure doses. Secondly, this trial aims to study whether hippocampal sparing in radiotherapy leads to measurable reduction in neurocognitive decline. |