Optimising Radiation Therapy in Head and Neck Cancers Using Functional Image-Guided Radiotherapy and Novel Biomarkers

NCT ID: NCT04242459

Last Updated: 2021-07-22

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 73 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-23
• Study Completion Date: 2024-05-01

Brief Summary

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:

1. 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.

2. 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).

1. Cohort 1: HPV-associated OPC consisting of 25 participants

2. Cohort 2: HPV-negative OPC consisting of a minimum of 10 patients and a maximum of 53 participants

3. Cohort 3: Base of Skull HNC consisting of 25 participants

Detailed Description

This study is looking at improving radiotherapy treatment for head and neck cancers by:

1. Repeating the radiotherapy planning scan at weeks 2 and 4 of treatment so that investigators can adapt the radiotherapy to changes to the shape of the cancer and the patient's body. These changes can affect the accuracy and the radiotherapy doses delivered.

2. Using a MR (magnetic resonance) scans to view and target the cancer with more precision.

3. Identifying HPV negative oropharyngeal cancer who are non-responders and increasing the radiotherapy dose.

The 3 groups of patients are:

1. Cancers of the oropharynx (middle of the throat) that test positive for HPV (human papilloma virus). If HPV is present, the cancer responds better to treatment and there is a higher chance of cure. In this group, the investigators aim is to reduce radiotherapy associated long-term side effects by sparing healthy tissue from high doses.

2. If the oropharyngeal cancers test negative for HPV, they are less likely to respond well to treatment. The investigator's department has shown that investigators can predict which patients will respond to treatment using a special type of MR scan. Investigators will increase the dose of radiotherapy to HPV negative patients who are predicted to be non-responders with the aim of improving the chance of cure.

3. Cancers that located at the base of the skull are not seen very well on CT scan. By using MR imaging, investigators can visualize the surrounding normal organs and the cancer better, target the cancer with more precision and adapt to changes to the healthy organs and tumour.

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.

Conditions

Head and Neck Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Feasibility Study

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

HPV associated OPC Participants

Participants will be treated initially with the standard radiotherapy dose of:

• 65 grays (Gy) in 30 fractions (2.17Gy per fraction) over 6 weeks to the primary and nodal tumour.
• 54Gy in 30 fractions (1.8Gy per fraction) over 6 weeks to the nodal areas at risk of harbouring microscopic disease

In the 2nd week and 4th week of treatment, the participants will undergo Adaptive Radiotherapy to account for anatomical changes.

Group Type: EXPERIMENTAL

Adaptive Radiotherapy

Intervention Type: 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

HPV negative OPC Participants - Radiotherapy dose escalation

Participants will be treated initially with the standard radiotherapy dose of:

• 65Gy in 30 fractions (2.17Gy per fraction) over 6 weeks to the primary and nodal tumour.
• 54Gy in 30 fractions (1.8Gy per fraction) over 6 weeks to the nodal areas at risk of harbouring microscopic disease

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.

Group Type: EXPERIMENTAL

Adaptive Radiotherapy

Intervention Type: 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

Base of Skull HNC Participants

Participants will be treated initially with the standard radiotherapy dose of:

• 65Gy in 30 fractions (2.17Gy per fraction) over 6 weeks to the primary and nodal tumour.
• 54Gy in 30 fractions (1.8Gy per fraction) over 6 weeks to the nodal areas at risk of harbouring microscopic disease

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.

Group Type: EXPERIMENTAL

Adaptive Radiotherapy

Intervention Type: 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

Interventions

Adaptive Radiotherapy

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

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

Feasibility study and Main Study:

• Participants with stage III/IV ((American Joint Committee (AJC) Tumour, Nodes, Metastasis (TMN) on Cancer Version 7)) head and neck cancer planned for primary radical chemo-radiotherapy OR induction chemotherapy followed by chemoradiotherapy with concomitant platinum-based chemotherapy.
• Age between 18 and 70 years.
• Participant can provide informed consent.
• World Health Organisation (WHO) performance status 0 - 1.
• Creatinine Clearance >50ml/minute
• Absolute Neutrophil Count ≥1.5 x10^9/L
• Platelets ≥100 x10^9/L
• Haemoglobin ≥90g/L

Feasibility Study:

• Participants with either HPV associated OPC, HPV negative OPC or Base of Skull HNC.

Low Risk HPV associated OPC:

• T1-3, N0-2c (AJCC 7th Edition, stage III and above)
• Participants with histologically proven squamous cell carcinoma of the head and neck
• p16 positive (defined as >70% cells staining positive)
• <10 year pack smoking history

HPV Associated OPC:

• Patients with histologically proven squamous cell carcinoma of the head and neck
• T1-3,N0-2c (AJCC 7th Edition, stage III and above) with ≥10 pack/ year smoking history
• p16 positive
• Any T4 and/or N3 regardless of smoking history
• Primary tumour size </=5cm

HPV negative OPC, hypopharyngeal or laryngeal cancer:

• Patients with histologically proven squamous cell carcinoma of the head and neck
• T1-4,N0-3 (AJCC 7th edition, stage III and above)
• p16 negative (if OPC)
• Primary tumour size </=5cm

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

• WHO performance status >=2.
• Participants with any previous malignancy except non-melanoma skin cancer.
• Participants with prior radiotherapy to the head and neck region
• Participants with contraindications to MRI scan.
• Participants with contraindications to IV contrast agents.
• Participants with renal failure

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Royal Marsden NHS Foundation Trust

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kee H. Wong, MD

Role: PRINCIPAL_INVESTIGATOR

Royal Marsden NHS Foundation Trust

Locations

Head and Neck Unit, Royal Marsden Hospital

Sutton, Surrey, United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

Abi Temple

Role: CONTACT

abigail.temple@rmh.nhs.uk

020 8661 3561 ext. 4020

Amy Scott

Role: CONTACT

amy.scott@rmh.nhs.uk

020 8661 3561 ext. 4020

Facility Contacts

Abi Temple

Role: primary

abigail.temple@rmh.nhs.uk

0208 661 3561 ext. 4020

Amy Scott

Role: backup

amy.scott@rmh.nhs.uk

0208 661 3561 ext. 4020

Other Identifiers

CCR4934

Identifier Type: -

Identifier Source: org_study_id