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This is a non-randomised study to develop personalised treatment approaches in participants with Locally Advanced Head and Neck Cancer (HNC) of the oropharynx and base of skull by integrating the use of MR-guided Adaptive Radiotherapy (MRgRT) and functional image-guided radiotherapy (FIgRT).
The study is made up of two parts:
Feasibility planning study consisting of a total of 13 patients. This will include patients with either Human papilomavirus-associated (HPV-associated) oropharyngeal cancer (OPC), Human papilomavirus-negative (HPV-negative) OPC or Base of Skull HNC.
Single centre prospective interventional phase I/II study (main study) made up of 3 independent arms (on the condition of success of the feasibility stage).
This study is looking at improving radiotherapy treatment for head and neck cancers by:
The 3 groups of patients are:
Investigators will also test if they can predict response to treatment by checking blood for fragments of the cancer and using a special MRI.
The study will be conducted at the Royal Marsden in Sutton only and will be followed up for 2 years.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Feasibility Study | No Intervention | This is a radiotherapy planning study to evaluate the feasibility to acquire longitudinal MRI scans during radiotherapy (prior to the main study) thus, participants will receive standard-of-care chemoradiation therapy (CRT) as per departmental protocol without any treatment adaptation. | |
| HPV associated OPC Participants | Experimental | Participants will be treated initially with the standard radiotherapy dose of:
In the 2nd week and 4th week of treatment, the participants will undergo Adaptive Radiotherapy to account for anatomical changes. |
|
| HPV negative OPC Participants - Radiotherapy dose escalation | Experimental | Participants will be treated initially with the standard radiotherapy dose of:
After 10 fractions the participants will be stratified into either "responders" or "non-responders" categories based on Apparent Diffusion Coefficients (ADC) response at week 2 of CRT. Participants classified as "responders" will complete treatment without any radiotherapy dose changes. Their radiotherapy treatment target volumes will be adapted at weeks 2 and 4 of CRT to account for volume changes to the tumour. The "non-responders" will undergo an increase in dose per fraction to Clinical Target Volume-1 (CTV-1) primary for fractions 11 to 30. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Adaptive Radiotherapy | Radiation | Determining the radiotherapy dose delivered to organs at risk (OAR) or to the target volume (dependent on what arm the participant is assigned to) through adaptive radiotherapy volume adaption planning |
| Measure | Description | Time Frame |
|---|---|---|
| Assess the feasibility of participants undergoing MR scan at baseline, week 2 and week 4 and feasibility of producing an adaptive radiotherapy plan | To calculate the proportion of participants who have successfully undergone the planned MRI scan at baseline and weeks 2 and 4 to determine the feasibility of producing an adaptive radiotherapy plan in the feasibility study. | Through feasibility study completion, estimated 6 months. |
| Compare the mean cumulative radiotherapy doses Main Study, Cohort 1: Compare the mean cumulative radiotherapy doses received by the parotid gland in an adaptive plan at weeks 3 and 5 to a non-adaptive plan | To determine the radiotherapy dose delivered to the parotid gland through adaptive radiotherapy volume adaptation planning compared to a non-adaptive radiotherapy approach in the main study, cohort 1. | Through main study treatment period, estimated 5 years. |
| Assess the safety of radiotherapy dose escalation by measuring the grades of acute radiation induced toxicities using NCI CTCAE v5.0 scores at 3 months | To assess the safety of radiotherapy dose escalation by measuring the grades of acute radiation induced toxicities which will be assessed using the NCI CTCAE v5.0 scores at 3 months in the main study, cohort 2. | Through main study treatment period, estimated 5 years. |
| Determine the Maximum Tolerated Dose (MTD) of the escalated radiotherapy dose as per the dose escalation criteria and stopping rules set out in the protocol | To determine the MTD of the escalated radiotherapy dose in the main study as per the dose escalation criteria and stopping rules as outlined in the protocol in the main study, cohort 2. | Through main study treatment period, estimated 5 years. |
| Compare the radiotherapy doses to the parotid glands calculated and recorded at baseline with doses from the adaptive plan at weeks 3 and 5 |
| Measure | Description | Time Frame |
|---|---|---|
| Calculate the proportion of patients who investigators can successfully produce an adaptive radiotherapy plan at weeks 3 and 5 within 1 week of their rescan to account for anatomical changes. | To calculate the proportion of patients who investigators can successfully produce an adaptive radiotherapy plan at weeks 3 and 5 within 1 week of their rescan to account for anatomical changes. To calculate whether investigators can create an adaptive radiotherapy plan at weeks 3 and 5. |
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Inclusion Criteria:
Feasibility study and Main Study:
Feasibility Study:
- Participants with either HPV associated OPC, HPV negative OPC or Base of Skull HNC.
Low Risk HPV associated OPC:
HPV Associated OPC:
HPV negative OPC, hypopharyngeal or laryngeal cancer:
Base of skull Head and Neck Cancer:
- Participants with histologically proven squamous cell carcinoma or undifferentiated carcinoma of the head and neck (sinonasal and nasopharynx)
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Abi Temple | Contact | 020 8661 3561 | 4020 | abigail.temple@rmh.nhs.uk |
| Amy Scott | Contact | 020 8661 3561 | 4020 | amy.scott@rmh.nhs.uk |
| Name | Affiliation | Role |
|---|---|---|
| Kee H. Wong, MD | Royal Marsden NHS Foundation Trust | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Head and Neck Unit, Royal Marsden Hospital | Recruiting | Sutton | Surrey | SM2 5PT | United Kingdom |
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| ID | Term |
|---|---|
| D006258 | Head and Neck Neoplasms |
| D009369 | Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
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The study will commence with a Feasibility Radiotherapy planning CT study consisting of 13 participants, then will recruit to the the main phase I/II interventional study consisting of 3 independent cohorts.
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| Base of Skull HNC Participants | Experimental | Participants will be treated initially with the standard radiotherapy dose of:
Participants will undergo standard treatment with 3 cycles of induction chemotherapy followed by chemo-radiotherapy dose. Their radiotherapy treatment will be adapted at weeks 2 and 4 of CRT to account for volume changes to the tumour. |
|
To calculate and record radiotherapy doses to the parotid glands at baseline and compare these to doses from the adaptive plan at weeks 3 and 5 in the main study, cohort 3. |
| Through main study treatment period, estimated 5 years. |
| Through feasibility study completion, estimated 6 months. |
| Calculate participants complete response rate at 3 months which is defined as no clinically visible, palpable or measurable disease on imaging or no residual tumour on neck dissection or directed biopsy | To calculate the complete response rate of participants at 3 months in the main study, cohorts 1-3. Response rate is defined as no clinically visible, palpable or measurable disease on imaging (PET-CT and/or MRI) or no residual tumour on neck dissection or directed biopsy. | Through main study treatment period, estimated 5 years. |
| Calculate the progression free survival which is defined as the time from entry into the study until disease progression or death (days) | To calculate the progression free survival which is defined as the time from entry into the study until disease progression or death in the main study, cohorts 1-3. This will be measured in whole days. | Through main study treatment period, estimated 5 years. |
| Calculate the disease specific survival which is defined as the time from entry into the study until death from any cause (days) | Calculate the disease specific survival which is defined as the time from entry into the study until death from any cause in the main study, cohorts 1-3. This will be measured in whole days. | Through main study treatment period, estimated 5 years. |
| Assess quality of life using the EORTC Quality of Life Questionnaire (QLQ) C30 version 3.0 with the associated Head and Neck module (HN35) | Assess quality of life using the EORTC Quality of Life Questionnaire (QLQ) C30 version 3.0 with the associated Head and Neck module (HN35) in the main study, cohorts 1-3. | Through main study treatment period, estimated 5 years. |
| Assess late radiation induced toxicities which will be recorded using the late effects in normal tissues subjective, objective, management and analytic scales (LENT SOMA) score and NCI CTCAE v5.0 late radiotherapy scoring systems. | To assess late radiation induced toxicities which will be recorded using the LENT SOMA score and NCI CTCAE v5.0 late radiotherapy scoring systems. The incidence and prevalence (highest grades) of late side effects of radiotherapy will be reported in the main study, cohorts 1-3. | Through main study treatment period, estimated 5 years. |
| Calculate the duration of acute radiation induced toxicities will be assessed using the NCI CTCAE v5.0 score (HPV associated OPC and skull base tumours); All participants will be evaluated assess xerostomia, mucositis, dysphagia and dermatitis | To calculate the duration of acute radiation induced toxicities will be assessed using the NCI CTCAE v5.0 score (HPV associated OPC and skull base tumours); All participants will be evaluated using the NCI CTCAE v5.0 score to assess xerostomia, mucositis, dysphagia and dermatitis in the main study, cohorts 1-3. | Through main study treatment period, estimated 5 years. |
| Assess the Incidence of feeding tube dependency at one year (HPV negative) which is defined as participant needing supplementation of nutrition by feeding tube. | To assess the Incidence of feeding tube dependency at one year (HPV negative) which is defined as participant needing supplementation of nutrition by feeding tube In the main study, cohorts 1-3. | Through main study treatment period, estimated 5 years. |
| Calculate the mean radiotherapy doses to the organs at risk (spinal cord, optic chiasm and brainstem) and target volume will be calculated and recorded at baseline and compared to doses from the adaptive plan at weeks 3 and 5. | To calculate the mean radiotherapy doses to the organs at risk (spinal cord, optic chiasm and brainstem) and target volume will be calculated and recorded at baseline and compared to doses from the adaptive plan at weeks 3 and 5 in the main study, cohort 3. | Through main study treatment period, estimated 5 years. |
| Calculate the mean radiotherapy doses to the organs at risk (salivary gland, spinal cord and brainstem) will be calculated and recorded at baseline and compared to doses from the adaptive plan at weeks 3 and 5. | To calculate the mean radiotherapy doses to the organs at risk (salivary gland, spinal cord and brainstem) will be calculated and recorded at baseline and compared to doses from the adaptive plan at weeks 3 and 5 in the main study, cohort 1. | Through main study treatment period, estimated 5 years. |