Clinical trial NCT04242459: Optimising Radiation Therapy in Head and Neck Cancers Using Functional Image-Guided Radiotherapy and Novel Biomarkers
Official title: Optimising Radiation Therapy in Head and Neck Cancers Using Functional Image-Guided Radiotherapy and Novel Biomarkers
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Head and Neck Cancer
Keywords: Cancer
Oropharynx
HPV
Base of Skull
Lead sponsor: Royal Marsden NHS Foundation Trust
Sponsor class: OTHER
First posted: 2020-01-27
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Assess the feasibility of participants undergoing MR scan at baseline, week 2 and week 4 and feasibility of producing an adaptive radiotherapy plan
timeFrame: Through feasibility study completion, estimated 6 months.
measure: 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
timeFrame: Through main study treatment period, estimated 5 years.
measure: 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
timeFrame: Through main study treatment period, estimated 5 years.
measure: 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
timeFrame: Through main study treatment period, estimated 5 years.
measure: Compare the radiotherapy doses to the parotid glands calculated and recorded at baseline with doses from the adaptive plan at weeks 3 and 5
timeFrame: Through main study treatment period, estimated 5 years.
Secondary outcomes:
measure: 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.
timeFrame: Through feasibility study completion, estimated 6 months.
measure: 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
timeFrame: Through main study treatment period, estimated 5 years.
measure: Calculate the progression free survival which is defined as the time from entry into the study until disease progression or death (days)
timeFrame: Through main study treatment period, estimated 5 years.
measure: Calculate the disease specific survival which is defined as the time from entry into the study until death from any cause (days)
timeFrame: Through main study treatment period, estimated 5 years.
measure: Assess quality of life using the EORTC Quality of Life Questionnaire (QLQ) C30 version 3.0 with the associated Head and Neck module (HN35)
timeFrame: Through main study treatment period, estimated 5 years.
measure: 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.
timeFrame: Through main study treatment period, estimated 5 years.
measure: 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
timeFrame: Through main study treatment period, estimated 5 years.
measure: Assess the Incidence of feeding tube dependency at one year (HPV negative) which is defined as participant needing supplementation of nutrition by feeding tube.
timeFrame: Through main study treatment period, estimated 5 years.
measure: 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.
timeFrame: Through main study treatment period, estimated 5 years.
measure: 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.
timeFrame: Through main study treatment period, estimated 5 years.
Other outcomes:
Locations:
city: Sutton
country: United Kingdom
facility: Head and Neck Unit, Royal Marsden Hospital
state: Surrey
Study officials:
affiliation: Royal Marsden NHS Foundation Trust
name: Kee H. Wong, MD
role: PRINCIPAL_INVESTIGATOR
References: