Randomized Trial of Avelumab-cetuximab-radiotherapy Versus SOCs in LA SCCHN (REACH)

NCT02999087 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: GORTEC 2017-01
• Study Type: interventional
• Target: 707
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to demonstrate that treatment with avelumab in combination with RT-cetuximab is superior to standard of care (SOC) cisplatin-RT and/or to SOC RT-cetuximab alone in terms of progression-free survival (PFS) in front-line patients with locally advanced SCCHN.

Conditions

HNSCC

Keywords

Head and Neck cancer; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Time between randomization and the first event among progression (per modified Response Evaluation Criteria in Solid Tumors (RECIST) version v1.1) and death, whatever the cause of death.

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 74 months

Secondary Outcomes (2)

• Overall survival

  From date of randomization until the date of death from any cause, assessed up to 74 months

• Safety: acute adverse events graded by NCI CTCAE v4.03

  From date of randomization to end of study, assessed up to 74 months

Study Arms (4)

Arm A Patient FIT

ACTIVE COMPARATOR

Lead-in phase (Day-8) : no treatment Concomitant radiotherapy phase : Radiotherapy by IMRT + cisplatin 100mg/m2 Maintenance phase : no treatment until follow-up phase

Drug: Cisplatin; Radiation: IMRT

Arm B Patient FIT

EXPERIMENTAL

Lead-in phase (Day-8) : Cetuximab 400mg/m2 and avelumab 10mg/kg Concomitant radiotherapy phase : Radiotherapy by IMRT + cetuximab 250mg/m2 and avelumab 10mg/kg Maintenance phase : avelumab 10mg/kg every 2 weeks during 12 months

Drug: Cetuximab; Drug: avelumab; Radiation: IMRT

Arm C Patient UNFIT

EXPERIMENTAL

Lead-in phase (Day-8) : Cetuximab 400mg/m2 and avelumab 10mg/kg Concomitant radiotherapy phase: Radiotherapy by IMRT + cetuximab 250mg/m2 and avelumab 10mg/kg Maintenance phase : avelumab 10mg/kg every 2 weeks during 12 months

Drug: Cetuximab; Drug: avelumab; Radiation: IMRT

Arm D Patient UNFIT

ACTIVE COMPARATOR

Lead-in phase (Day-8): Cetuximab 400mg/m2 Concomitant radiotherapy phase: Radiotherapy by IMRT + cetuximab 250mg/m2 Maintenance phase : no treatment until follow-up phase

Drug: Cetuximab; Radiation: IMRT

Interventions

Cetuximab DRUG

Loading dose of 400 mg/m² IV on Day-8, followed by weekly dose of 250 mg/m² IV during the whole course of RT.

Arm B Patient FIT; Arm C Patient UNFIT; Arm D Patient UNFIT

avelumab DRUG

IV infusion of avelumab (10 mg/kg over 1 hour) once every 2 weeks. Avelumab will start on Day-8 together with cetuximab and subsequently every 2 weeks during the course of RT. Avelumab with be continued every 2 weeks for an additional 12 months following RT.

Arm B Patient FIT; Arm C Patient UNFIT

Cisplatin DRUG

100 mg/m² IV after hyperhydration and at a maximal rate of 1 mg/min, on days 1, 22, 43.

Arm A Patient FIT

IMRT RADIATION

RT will be performed using IMRT (intensity modulated radiotherapy), with a simultaneous integrated boost (SIB) technique. RT dose to the GTV will be 69.96 Gy in 2.12 Gy daily fractions over 6.5 weeks (33 fractions). Prophylactic dose will be 52.8 Gy in 1.6 Gy daily fractions over 6.5 weeks (33 fractions).

Arm A Patient FIT; Arm B Patient FIT; Arm C Patient UNFIT; Arm D Patient UNFIT

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≤ 80 years
• Performance Status ECOG 0-1
• Squamous cell carcinoma, previously untreated
• Stage III, stage IVa (i.e. operable, but not operated) or IVb (non resectable)
• Oral cavity, oropharynx, hypopharynx or larynx
• Availability of pre-treatment tumour tissue sample (for p16 \& PD -L1 expression, TILs and immune landscape)
• Recording of alcohol consumption and smoking history
• Determination of the patient's ability to receive cisplatin 100 mg /m2 for 3 cycles (fit / unfit)\*
• Written informed consent
• Criteria for determining if a patient is fit for receiving high dose cisplatin:
• Calculated creatinin clearance ≥ 60 mL/min as determined by the modified. method of Cockcroft and Gault or by the EDTA method
• Absolute neutrophil count ≥1 500/μL, platelets ≥100 000/μL, hemoglobin ≥ 10 g/dL, aspartate (AST) and alanine transaminase (ALT) less than 2 times the upper limit of the normal range (ULN), total bilirubin ≤ 1.5 mg/dL, serum albumin \> 35 g/L
• Peripheral neuropathy \< grade 2
• No clinical hearing loss (confirmed by audiogram)
• Cardiac function compatible with hyperhydration; Left ventricular ejection fraction within the institutional normal ranges as measured by echocardiogram

You may not qualify if:

• Nasopharyngeal, paranasal sinuses, nasal cavity tumors or thyroid cancers
• Squamous cell carcinoma involving cervical neck nodes with unknown primary site
• Metastatic disease (stage IVc)
• Viral infection (HIV, Hepatitis B/C)
• Autoimmune disease
• Immunodeficiency or immunosuppressive therapy
• Active CNS disease
• Interstitial lung disease
• Active infection
• Any prior or current treatment for invasive head and neck cancer. This will include but is not limited to: prior tyrosine kinase inhibitors, any monoclonal antibody, induction chemotherapy, prior surgical resection or RT, or use of any investigational agent
• Weight loss of \> 10% during the last 4 weeks (except if renutrition with a feeding tube is planned before the onset of treatment or is ongoing)
• Concurrent treatment with any other systemic anti-cancer therapy that is not specified in the protocol
• Concomitant treatment with any drug on the prohibited medication list such as live vaccines
• History of other malignancy within the last 3 years (exception of in situ carcinoma and skin carcinomas)
• Significant disease which, in the judgment of the investigator, as a result of the medical interview, physical examinations, or screening investigations would make the patient inappropriate for entry into the trial

Sponsors & Collaborators

• Groupe Oncologie Radiotherapie Tete et Cou: lead
• UNICANCER: collaborator

Study Sites (1)

Centre Hospitalier Bretagne Sud

Lorient, 56322, France

Location

Related Publications (1)

• Tao Y, Auperin A, Sun X, Sire C, Martin L, Coutte A, Lafond C, Miroir J, Liem X, Rolland F, Even C, Nguyen F, Saada E, Maillard A, Colin-Batailhou N, Thariat J, Guigay J, Bourhis J. Avelumab-cetuximab-radiotherapy versus standards of care in locally advanced squamous-cell carcinoma of the head and neck: The safety phase of a randomised phase III trial GORTEC 2017-01 (REACH). Eur J Cancer. 2020 Dec;141:21-29. doi: 10.1016/j.ejca.2020.09.008. Epub 2020 Oct 24.

  PMID: 33125944 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms

Interventions

Cetuximab; avelumab; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2016
• First Posted: December 21, 2016
• Study Start: September 14, 2017
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: May 7, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)