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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02999087
Recruitment Status : Active, not recruiting
First Posted : December 21, 2016
Last Update Posted : November 4, 2020
Sponsor:
Collaborator:
UNICANCER
Information provided by (Responsible Party):
Groupe Oncologie Radiotherapie Tete et Cou

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.

Condition or disease Intervention/treatment Phase
HNSCC Drug: Cetuximab Drug: avelumab Drug: Cisplatin Radiation: IMRT Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 707 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III Randomized Trial of Avelumab-cetuximab-Radiotherapy Versus Standards of Care in Locally Advanced Squamous Cell Carcinoma of the Head and Neck
Actual Study Start Date : September 14, 2017
Estimated Primary Completion Date : December 2027
Estimated Study Completion Date : December 2027

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: 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

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

Radiation: 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).

Experimental: 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

Drug: 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.

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.

Radiation: 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).

Experimental: 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

Drug: 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.

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.

Radiation: 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).

Active Comparator: 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

Drug: 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.

Radiation: 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).




Primary Outcome Measures :
  1. Progression free survival [ Time Frame: 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 ]
    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.


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: From date of randomization until the date of death from any cause, assessed up to 74 months ]
  2. Safety: acute adverse events graded by NCI CTCAE v4.03 [ Time Frame: From date of randomization to end of study, assessed up to 74 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02999087


Locations
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France
Centre Hospitalier Bretagne Sud
Lorient, France, 56322
Sponsors and Collaborators
Groupe Oncologie Radiotherapie Tete et Cou
UNICANCER
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Groupe Oncologie Radiotherapie Tete et Cou
ClinicalTrials.gov Identifier: NCT02999087    
Other Study ID Numbers: GORTEC 2017-01
First Posted: December 21, 2016    Key Record Dates
Last Update Posted: November 4, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Groupe Oncologie Radiotherapie Tete et Cou:
Head and Neck cancer
Immunotherapy
Additional relevant MeSH terms:
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Cetuximab
Antineoplastic Agents
Antineoplastic Agents, Immunological