Post-operative adjuvant treatment for HPV-positive tumours

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Cardiff University

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

27 Oct 2020 → ongoing

Decision date (initial)

2025-01-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-516673-68-00

EudraCT number

2014-003392-32

ClinicalTrials.gov

NCT02215265

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy

1. To demonstrate if swallowing function can be improved and toxicities reduced following transoral surgery for HPV-positive oropharyngeal cancer, by reducing the intensity of adjuvant treatment protocols.
2. To demonstrate the non-inferiority of reducing the intensity of adjuvant treatment protocols in terms of overall survival

Secondary objectives 6

1. Standardisation of transoral surgery for OPSCC by rigorous application of surgical standards.
2. The credentialing of participating surgeons (not applicable in France)
3. Standardisation of surgical margin assessment after transoral surgery and examination of the clinical-pathological correlates of HPV-positive OPSCC by central pathology review of specimens.
4. Development of a standardised, multi-faceted swallowing assessment tool for patients undergoing treatment for OPSCC, applicable by Speech and Language Therapists (SLTs) in multiple centres.
5. Development of a RTTQA package and adjuvant Intensity Modulated Radiotherapy (IMRT) protocol for OPSCC. Dose/volume data for swallowing structures will be recorded so that the relationship between long-term swallowing function (phase II endpoint) and dose/volumes received by the swallowing organs can be prospectively analysed.
6. A programme of translational research will be developed to utilize PATHOS clinical samples.

Conditions and MedDRA coding

Human papillomavirus (HPV)-positive oropharyngeal cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. Histologically confirmed or suspected squamous cell carcinoma of the oropharynx.
2. UICC/AJCC TNM 7th edition stage T1-T3*, N0-N2b (or UICC TNM 8th edition stage T1-T3, N0-N1) disease.
3. Multidisciplinary team (MDT) decision to treat with primary transoral resection and neck dissection.
4. Patients considered fit for surgery and adjuvant radiotherapy
5. Aged 18 or over.
6. Written informed consent provided (not applicable for France).
7. Patients must be affiliated to a Social Security System (applicable for France only)
8. Patient must have signed informed consent prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient’s consent (applicable for France only).
9. Patients must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures (applicable for France only).
10. Group B : Fit to undergo radiotherapy.
11. Group B : HPV positive by both P16 and either High Risk HPV In-Situ Hybridization (ISH) or validated Polymerase Chain Reaction (PCR) technique
12. Group C : Fit for, and able to potentially benefit from chemoRT, as decided by an MDT.
13. Group C : Willing to be treated with chemotherapy
14. Group C : HPV positive by both P16 and either High Risk HPV In-Situ Hybridization (ISH) or validated Polymerase Chain Reaction (PCR) technique
15. Group C : Bone marrow reserve adequate for chemotherapy (i.e. absolute neutrophil count (ANC) ≥ 1.5 x 109/l and platelet count ≥ 100 x 109/l).
16. Group C : Adequate GFR for Cisplatin chemotherapy, defined as GFR ≥ 50 ml/min.

Exclusion criteria 20

1. Known HPV negative squamous cell carcinomas of the head and neck: A negative result for p16 Immunohistochemistry automatically excludes a patient from the trial. If initial p16 testing is positive but High-Risk HPV (HR HPV) In-Situ Hybridization (ISH) / Polymerase Chain Reaction (PCR) does not demonstrate the presence of HR HPV DNA, the patient will also be excluded. Patients who are p16 positive may complete swallowing assessments, excluding videofluoroscopy, and surgery whilst HR HPV DNA status is being determined (with recourse to central concordance testing, if appropriate, for UK centres). HPV positivity, as determined by p16 and the demonstration of HR HPV DNA is essential before patients undergo videofluoroscopy or randomisation.
2. T4 and/or T1-T3 tumours where transoral surgery is considered not feasible.
3. UICC/AJCC TNM 7th edition N2c-N3 nodal disease (or UICC/AJCC TNM 8th edition N2-N3 nodal disease).
4. Patients for whom transoral surgery and neck dissection is not considered the primary treatment modality.
5. Current smokers with clinically staged N2b disease (including smokers up to 6 months before diagnosis), even if HPV-positive. Vaping is permitted and should be considered as non-smoking status.
6. Any pre-existing medical condition likely to impair swallowing function and/ or a history of pre-existing swallowing dysfunction prior to index oropharyngeal cancer.
7. Patients with distant metastatic disease as determined by routine pre-operative staging radiological investigations e.g., CT thorax and upper abdomen or PET-CT.
8. Patients with a history of malignancy in the last 5 years, except basal cell carcinoma of the skin or carcinoma in-situ of the cervix.
9. Women who are pregnant or breastfeeding and fertile women who will not be using contraception during the trial.
10. Persons deprived of their liberty or under protective custody or guardianship (applicable for France only)
11. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons (applicable for France only).
12. Group B : pN2c or pN3 as per UICC/AJCC TNM 7th edition.
13. Group C : Myelosuppression
14. Group C : Pre-existing renal impairment (GFR < 50ml/min).
15. Group C : History of significant cardiac conditions, arteriopathy, or other medical conditions that preclude the use of Cisplatin and IV hydration.
16. Group C : Clinically significant hearing impairment sufficient to affect daily living (as reported by the patient) and/or pre-existing tinnitus.
17. Group C : Pre-existing peripheral neuropathy which precludes the use of Cisplatin.
18. Group C : Hypersensitivity to the active substance or other platinum compounds or to any of the excipients listed in the SPC.
19. Group C : Dehydrated condition (pre- and post-hydration is required to prevent serious renal dysfunction).
20. Group C : pN2c or pN3 as per UICC/AJCC TNM 7th edition.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival and swallowing function as measured by the MD Anderson Dysphagia Inventory (MDADI) score.

Secondary endpoints 4

1. Swallowing panel measurements including qualitative and quantitative swallowing assessments as described previously.
2. QOL (using EORTC QLQ C30 and HN35 questionnaires).
3. Acute and late toxicity, assessed using NCI CTCAE criteria version 4.03
4. Overall survival, disease free survival, locoregional control, distant metastases.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Cardiff University

Sponsor organisation

Cardiff University

Address

Neuadd Meirionnydd, Heath Park Way, Heath Heath Park Way Heath

City

Cardiff

Postcode

CF14 4YU

Country

United Kingdom

Scientific contact point

Organisation

Cardiff University

Contact name

Chris Shaw

Public contact point

Organisation

Cardiff University

Contact name

Chris Shaw

Locations

2 EU/EEA countries · 25 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications