Phase II Evaluation of Durvalumab Combined with Radiotherapy in T1-T4 N0-N2b Squamous Cell Carcinoma of the Head and Neck Without Prophylactic Neck Irradiation

Trial ID: 2024-513977-31-00
Protocol: GORTEC 2018-02
Sponsor: Groupe Oncologie Radiotherapie Tete Cou

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Diseases & Conditions

Squamous cell carcinoma of head and neck

Objectives

The primary objective of this phase II clinical trial is to evaluate the **regional (cervical) control** of **durvalumab** treatment combined with radiotherapy in patients with untreated squamous cell carcinoma of the head and neck. This evaluation focuses on the tumor site, including the primary tumor and the invaded cervical lymph nodes, without prophylactic irradiation of the N0 regions. This is clinically relevant as it aims to determine the efficacy of this treatment approach in controlling the disease locally, potentially reducing the need for more extensive radiation therapy and its associated side effects.

Secondary objectives include:

Assessing the tolerance and safety of durvalumab combined with radiotherapy, focusing on treatment-related adverse events of grade ≥ 2 according to the NCI CTCAE v5.0.
Evaluating local control at the site of the primary tumor.
Assessing locoregional (cervical) control.
Evaluating final cervical control, including salvage surgery and/or radiotherapy in case of lymph node relapse.
Monitoring distant metastases control.
Assessing overall survival.
Evaluating the objective response rate.
Assessing progression-free survival.
Evaluating health-related quality of life.
Identifying immune or biological markers potentially associated with patient outcomes.

Participants

The clinical trial involves participants diagnosed with **untreated squamous cell carcinoma of the head and neck**. The study population includes both male and female subjects aged over 18 years, with no upper age limit specified. Participants are required to have a Performance Status of ECOG 0-2 and must not have received prior treatment for their carcinoma. The trial does not involve a vulnerable population. The selection criteria include individuals with T1-T4 N0-N2b squamous cell carcinoma, with specific clinical statuses and fragility criteria, such as multiple comorbidities or being judged unfit for certain chemotherapies. Participants must have a documented p16 disease status for oropharyngeal tumors and meet specific renal function criteria. The sponsor has not provided information regarding the total number of participants in the trial.

Plans and Procedures

The clinical trial is designed to evaluate the efficacy and safety of **durvalumab** in combination with radiotherapy for the treatment of untreated **squamous cell carcinoma of the head and neck**. This is a phase II, randomized, double-blind, controlled trial. The trial aims to assess the regional control of the disease without prophylactic neck irradiation. The study is expected to commence on July 24, 2024, and conclude by July 17, 2026, with an estimated duration of two years.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to determine eligibility based on criteria such as age, performance status, and specific medical conditions. Following successful screening, participants will be randomized to receive the investigational treatment. The trial includes multiple follow-up visits to monitor treatment response, adverse events, and overall health status. The end-of-study visit will evaluate the primary endpoint, which is the regional nodal control rate at one year, along with secondary endpoints such as adverse events, local control, and overall survival.

The expected length of participant involvement is approximately eight months, corresponding to the maximum treatment period. Conditions that may lead to early termination from the study include significant adverse events, disease progression, or withdrawal of consent. The investigational product, IMFINZI 50 mg/mL concentrate for solution for infusion, will be administered as a solution for infusion, with a maximum daily dose of 1500 mg and a total dose not exceeding 12375 mg. The trial is not classified as a low-intervention study and is conducted under the sponsorship of AstraZeneca AB.

Treatment

The clinical trial involves the administration of **IMFINZI** (durvalumab), a **concentrate for solution for infusion**. The pharmaceutical form is a solution for infusion, and it is administered intravenously. The active substance, **durvalumab**, is a protein-based therapeutic agent, specifically classified under the ATC code L01XC28. The concentration of the solution is 50 mg/mL, and the maximum daily dose is 1500 mg, with a total maximum dose of 12375 mg over the treatment period. The treatment is administered over a maximum period of 8 weeks. The administration schedule and dosage are designed to evaluate the regional control of durvalumab treatment in combination with radiotherapy in patients with squamous cell carcinoma of the head and neck.

In this study, durvalumab is used for a therapeutic indication different from its original authorization. The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol. The trial aims to assess the efficacy of durvalumab in conjunction with radiotherapy, without prophylactic neck irradiation, in controlling the disease in the specified patient population.

Efficacy

Efficacy in this clinical trial will be assessed primarily through the **regional (neck) nodal control rate at 1 year**. This primary endpoint will evaluate the effectiveness of the treatment regimen, which combines **durvalumab** with radiotherapy, in controlling nodal disease in patients with squamous cell carcinoma of the head and neck. Secondary endpoints will include a range of measures to provide a comprehensive assessment of treatment efficacy and safety. These include the evaluation of early and late adverse events of grade ≥ 2 according to the CTCAE V5.0, local control at the primary site, locoregional nodal and primary site control rate, distant metastases control rate, and ultimate regional control including salvage surgery and/or salvage radiotherapy. Additionally, overall survival, objective response rate, progression-free survival, and quality of life scores (QLQ C30 and QLQ-H&N35) at baseline, 3, 12, and 24 months post-radiotherapy will be measured. These endpoints will be assessed using validated scales and methodologies appropriate for each parameter, ensuring a robust evaluation of the treatment's efficacy.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Age > 18 years with no upper limit
Performance Status ECOG 0-2
Squamous cell carcinoma, previously untreated
T1-T4 with clinical status N0-N1, N2a or N2b non palpable, with only homolateral lymph node in radiological examinations.
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
Oral cavity, oropharynx, hypopharynx or larynx
Documentation of p16 disease (HPV status for oropharyngeal tumor)
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

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Exclusion Criteria

Nasopharyngeal, paranasal sinuses, nasal cavity tumors or thyroid cancers
Metastatic disease
Any prior or current treatment for invasive head and neck cancer
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
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)
Other severe acute or chronic medical conditions including pneumonitis, pulmonary fibrosis
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])
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