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

NCT04242459 | Unknown Phase 1 DMC

• 1 other identifier: CCR4934
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 1

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. 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. 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).
3. 3.Cohort 1: HPV-associated OPC consisting of 25 participants
4. 4.Cohort 2: HPV-negative OPC consisting of a minimum of 10 patients and a maximum of 53 participants
5. 5.Cohort 3: Base of Skull HNC consisting of 25 participants

Conditions

Head and Neck Cancer

Keywords

Cancer; Oropharynx; HPV; Base of Skull

Outcome Measures

Primary Outcomes (5)

• 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

  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.

Secondary Outcomes (10)

• 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.

  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

  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)

  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)

  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)

  Through main study treatment period, estimated 5 years.

Study Arms (4)

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: * 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.

Radiation: Adaptive Radiotherapy

HPV negative OPC Participants - Radiotherapy dose escalation

EXPERIMENTAL

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.

Radiation: Adaptive Radiotherapy

Base of Skull HNC Participants

EXPERIMENTAL

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.

Radiation: Adaptive Radiotherapy

Interventions

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

Base of Skull HNC Participants; HPV associated OPC Participants; HPV negative OPC Participants - Radiotherapy dose escalation

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Royal Marsden NHS Foundation Trust: lead

Study Sites (1)

Head and Neck Unit, Royal Marsden Hospital

Sutton, Surrey, SM2 5PT, United Kingdom

RECRUITING

MeSH Terms

Conditions

Head and Neck Neoplasms; Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site

Study Officials

• Kee H. Wong, MD

  Royal Marsden NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Abi Temple

CONTACT

020 8661 3561; abigail.temple@rmh.nhs.uk

Amy Scott

CONTACT

020 8661 3561; amy.scott@rmh.nhs.uk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 8, 2019
• First Posted: January 27, 2020
• Study Start: October 23, 2019
• Primary Completion: May 1, 2024
• Study Completion: May 1, 2024
• Last Updated: July 22, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)