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

NCT ID: NCT02999087

Last Updated: 2025-05-07

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 707 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-14
• Study Completion Date: 2027-12-31

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.

Detailed Description

This open-label, randomized, controlled, multicenter phase III study will include 688 patients with LA SCCHN (420 fit for HD cisplatin and 268 unfit for HD cisplatin), histologically confirmed who had not received previous treatment for this setting. The study is designed with the primary objective of demonstrating that treatment with avelumab in combination with cetuximab-RT is superior to SOC Cisplatin-RT or cetuximab-RT alone in terms of PFS. Randomization will assign the 2 treatment arms of each cohort with a 1:1 ratio. In each cohort (fit for cisplatin and unfit for cisplatin), the randomization will be stratified for the 2 most established prognostic factors N stage (N0-N1 vs N2-3) and p16 expression (OPC p16+ versus OPC p16- or non OPC). All patients will be followed until death or at least 60 months.

Conditions

HNSCC

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A Patient FIT

Lead-in phase (Day-8) : no treatment

Concomitant radiotherapy phase : Radiotherapy by IMRT + cisplatin 100mg/m2

Maintenance phase : no treatment until follow-up phase

Group Type: ACTIVE_COMPARATOR

Cisplatin

Intervention Type: DRUG

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

IMRT

Intervention Type: 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 B Patient FIT

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

Group Type: EXPERIMENTAL

Cetuximab

Intervention Type: 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.

avelumab

Intervention Type: 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.

IMRT

Intervention Type: 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 C Patient UNFIT

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

Group Type: EXPERIMENTAL

Cetuximab

Intervention Type: 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.

avelumab

Intervention Type: 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.

IMRT

Intervention Type: 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 D Patient UNFIT

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

Group Type: ACTIVE_COMPARATOR

Cetuximab

Intervention Type: 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.

IMRT

Intervention Type: 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).

Interventions

Cetuximab

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.

Intervention Type: DRUG

avelumab

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.

Intervention Type: DRUG

Cisplatin

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

Intervention Type: DRUG

IMRT

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).

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

1. Age ≤ 80 years

2. Performance Status ECOG 0-1

3. Squamous cell carcinoma, previously untreated

4. Stage III, stage IVa (i.e. operable, but not operated) or IVb (non resectable)

5. Oral cavity, oropharynx, hypopharynx or larynx

6. Availability of pre-treatment tumour tissue sample (for p16 & PD -L1 expression, TILs and immune landscape)

7. Recording of alcohol consumption and smoking history

8. Determination of the patient's ability to receive cisplatin 100 mg /m2 for 3 cycles (fit / unfit)*

9. 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

Exclusion Criteria

1. Nasopharyngeal, paranasal sinuses, nasal cavity tumors or thyroid cancers

2. Squamous cell carcinoma involving cervical neck nodes with unknown primary site

3. Metastatic disease (stage IVc)

4. Viral infection (HIV, Hepatitis B/C)

5. Autoimmune disease

6. Immunodeficiency or immunosuppressive therapy

7. Active CNS disease

8. Interstitial lung disease

9. Active infection

10. 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

11. 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)

12. Concurrent treatment with any other systemic anti-cancer therapy that is not specified in the protocol

13. Concomitant treatment with any drug on the prohibited medication list such as live vaccines

14. History of other malignancy within the last 3 years (exception of in situ carcinoma and skin carcinomas)

15. 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

16. Known hypersensitivity reaction to study drugs

17. Any social, personal, medical and/or psychological factor(s) that could interfere with the observance of the patient to the protocol and/or the follow-up and/or the signature of the informed consent.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

UNICANCER

OTHER

Sponsor Role: collaborator

Groupe Oncologie Radiotherapie Tete et Cou

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Centre Hospitalier Bretagne Sud

Lorient, , France

Countries

France

References

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.

Reference Type: DERIVED

PMID: 33125944 (View on PubMed)

Other Identifiers

GORTEC 2017-01

Identifier Type: -

Identifier Source: org_study_id