A Phase II Trial of Radiotherapy (RT)-Durvalumab Without Prophylactic Neck Irradiation in Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Groupe Oncologie Radiotherapie Tete et Cou2 sites in 1 country61 target enrollmentJuly 17, 2019

ConditionsHNSCC

InterventionsDurvalumab

DrugsDurvalumab

Overview

Phase: Phase 2
Intervention: Durvalumab
Conditions: HNSCC
Sponsor: Groupe Oncologie Radiotherapie Tete et Cou
Enrollment: 61
Locations: 2
Primary Endpoint: Regional (neck) nodal control rate
Status: Active, not recruiting
Last Updated: 12 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This study evaluate the regional (neck) nodal control of durvalumab in combination with RT restricted to the primary tumor and the immediately adjacent nodal level (i.e. without prophylactic neck irradiation) in N0 patients with SCCHN.

Detailed Description

There is a strong rationale for testing this new paradigm of RT for SCCHN without prophylactic neck irradiation, being replaced by immune stimulation via the combination of RT and Programmed Death-1 (PD-L1) inhibition with durvalumab, due to: * The unmet medical need for new treatments, better tolerated and " as " or " more " effective than the current Standard Of Care (SOC) * The need to decrease radiation-induced toxicity, especially in fragile patients * The added toxicity due to elective nodal irradiation * The strong rationale to combine RT and PD-L1 inhibition * The potential immune suppressive effect of large field prophylactic neck irradiation It is hypothesized this innovative concept to be safe in the context of this study for the following reasons: * The rate of relapse in the neck is expected to be low in Magnetic Resonnance Imaging (MRI) \& PET-CT N0 neck * A non-irradiated neck can be easily monitored, clinically and by imaging * Most of the potential relapses in the neck are expected to be salvaged by surgery and/or RT * The preventive irradiation of N0 regions is not anymore performed for others lymphophilic cancers (lymphoma, Non-Small Cell Lung Cancer (NSCLC)). The combination of durvalumab with RT restricted to the primary tumor site and immediate adjacent nodal area will achieve a similarly regional (nodal) control rate than standard RT including large prophylactic neck irradiation (regional recurrence \< 10 %. This study will include patients with early (T1-T2 N0) or locally advanced SCCHN (T3-4 N0), histologically proven who had not received previous treatment for this setting. The study is designed with the primary objective of demonstrating that RT without large prophylactic irradiation in combination with durvalumab is effective in terms of regional control. All patients will be followed until death or at least 36 months.

Registry

clinicaltrials.gov

Start Date

July 17, 2019

End Date

August 2026

Last Updated

12 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Groupe Oncologie Radiotherapie Tete et Cou

Responsible Party

Sponsor

Eligibility Criteria

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 or N2a-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 oncogeratric 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)

Exclusion Criteria

•Nasopharyngeal, paranasal sinuses, nasal cavity tumors or thyroid cancers
•Metastatic disease
•Active CNS 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.
•Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis
•Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the investigator
•Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable
•History of leptomeningeal carcinomatosis
•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)

Arms & Interventions

RT-durvalumab

durvalumab at fixed dose of 1120 mg on Day1 of RT and every 3 weeks during the RT. Durvalumab with be continued at a fixed dose of 1500 mg every 4 weeks during 6 months following RT.

Intervention: Durvalumab