Trial evaluating the tolerance and safety of durvalumab - radiotherapy combination for treatment of cancers of the head and neck

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Groupe Oncologie Radiotherapie Tete Cou

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

17 Jul 2019 → 9 Mar 2026

Decision date (initial)

2024-07-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-513977-31-00

EudraCT number

2018-001976-39

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

To evaluate the regional (cervical) control of durvalumab treatment combined with radiotherapy to the tumor site including the primary tumor and the invaded cervical lymph nodes and the 1st lymph node level, without prophylactic irradiation of the N0 regions in patients with T1-T4 N0-N2b squamous cell carcinoma of the head and neck.

Secondary objectives 10

1. Tolerance and safety of durvalumab combined with RT, as early and late treatmentrelated adverse events of grade ≥ 2 according to the NCI CTCAE v5.0
2. Local control (site of the primary tumor)
3. Locoregional (cervical) control
4. Final cervical control including salvage surgery and/or RT in case of lymph node relapse
5. Distant metastases control
6. Overall survival
7. Objective response rate
8. Progression-free survival
9. Health-related quality of life
10. Immune or biological markers potentially associated with patient outcome

Conditions and MedDRA coding

Untreated squamous cell carcinoma of the head and neck

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Age > 18 years with no upper limit
2. Performance Status ECOG 0-2
3. Squamous cell carcinoma, previously untreated
4. T1-T4 with clinical status N0-N1, N2a or N2b non palpable, with only homolateral lymph node in radiological examinations.
5. Patient with at least one of these fragility criteria : o Status ECOG 1 with multiple comorbidities, at least 2 pathologies with grade ≥ 2 (renal and/or cardiac and/or vascular and/or hepatic, and/or neurologic, and/or pulmonary) o Status ECOG = 2 o Age ≥ 70 , judged unfit with oncogeriatric evaluation by EGE (ELAN Geriatric Evaluation) test or unable to receive cisplatine or Carboplatine- 5FU (at least one criteria listed below*) * Criteria for determining if a patient is unfit for receiving cisplatine or carbo-5FU : Calculated creatinine clearance ≤ 60 mL/min as determined by the modified. method of Cockcroft and Gault or glomerular filtration rate ≤ 60 mL/min/1.73m² (CKD-EPI method recommended) Haemoglobin < 10 g/dL, aspartate (AST) and alanine transaminase (ALT) more than 2 times the upper limit of the normal range (ULN), serum albumin ≤35 g/L, Absolute neutrophil count ≤ 1 500/μL, platelets ≤ 100 000/μL or total bilirubin ≥ 1.5 mg/dL Cardiac function not compatible with hyperhydration or significant heart disease Weight loss > 15% in 2 months
6. Oral cavity, oropharynx, hypopharynx or larynx
7. Documentation of p16 disease (HPV status for oropharyngeal tumor)
8. Glomerular filtration rate (GFR) >40 mL/min/1.73m2 (CKD-EPI method recommended) or Calculated creatinine clearance CL>40 mL/min by the Cockcroft- Gault formula

Exclusion criteria 8

1. Nasopharyngeal, paranasal sinuses, nasal cavity tumors or thyroid cancers
2. Metastatic disease
3. Any prior or current treatment for invasive head and neck cancer
4. Any unresolved toxicity NCI CTCAE v5.0 Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. a. Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis b. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the investigator
5. Body weight ≤ 30 kg and/or weight loss of ≥ 15% during the last 4 weeks (except if renutrition with a feeding tube is planned before the onset of treatment or is ongoing)
6. Other severe acute or chronic medical conditions including pneumonitis, pulmonary fibrosis
7. Active autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc])
8. Uncontrolled intercurrent illness, including but not limited to, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Regional (neck) nodal control rate at 1 year

Secondary endpoints 9

1. Early and late adverse events of grade ≥ 2, according to the CTCAE V5.0
2. Local control at the primary site
3. Locoregional nodal + primary site control rate
4. Distant metastases control rate
5. Ultimate regional control including salvage surgery and/or salvage RT)
6. Overall survival
7. Objective Response Rate
8. Progression-free survival
9. QLQ C30 and QLQ-H&N35 scores at baseline, 3, 12 and 24 months post RT

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Groupe Oncologie Radiotherapie Tete Cou

Sponsor organisation

Groupe Oncologie Radiotherapie Tete Cou

Address

4 B Rue Emile Zola

City

Tours

Postcode

37000

Country

France

Scientific contact point

Organisation

Groupe Oncologie Radiotherapie Tete Cou

Contact name

Dr Joël CASTELLI

Public contact point

Organisation

Groupe Oncologie Radiotherapie Tete Cou

Contact name

Laura SINIGAGLIA

Locations

1 EU/EEA country · 19 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 4 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