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Randomized trial of avelumab-cetuximab-Radiotherapy versus standards of care in the head and neck cancers

Phase 1
Conditions
Squamous cell carcinoma, previously untreatedStage III, stage IVa (i.e. operable, but not operated) or IVb (non resectable)Oral cavity, oropharynx, hypopharynx or larynx
MedDRA version: 20.0Level: PTClassification code 10060121Term: Squamous cell carcinoma of head and neckSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]
Registration Number
EUCTR2016-004383-19-FR
Lead Sponsor
GORTEC
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
All
Target Recruitment
Not specified
Inclusion Criteria

1.Age > 18 years and = 80 years.
2.Performance Status ECOG 0-1
3.Histologically confirmed 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 PD -L1 expression, TILs and immune lanscape)
7. Documentation of p16 disease (HPV status for oropharyngeal tumor)
8.Recording of alcohol consumption and smoking history
9.Determination of the patient’s ability to receive cisplatin 100 mg/m2 for 3 cycles (fit / unfit)*
10.Written informed consent

* Criteria for determining if a patient is fit for receiving high dose cisplatin :
-Calculated creatinine clearance = 50 mL/min as determined by the CKD-EPI method
-Absolute neutrophil count =1 500/µL, platelets =100 000/µL, haemoglobin = 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 sensorineural hearing loss = grade 2 (confirmed by audiogram)
-Cardiac function compatible with hyperhydration with no significant heart disease

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 688
F.1.3 Elderly (>=65 years)
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Nasopharyngeal, paranasal sinuses, nasal cavity tumours or thyroid cancers
2.Squamous cell carcinoma involving cervical neck nodes with unknown primary site
3.Metastatic disease (stage IVc)
4.Active viral infection (HIV, Hepatitis B/C)
5.Active autoimmune disease
6.Active immunodeficiency or ongoing 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.Concurrent treatment with any other systemic anti-cancer therapy that is not specified in the protocol

12.Concomitant treatment with any drug on the prohibited medication list such as live vaccines (for details, see the protocol)

13.History of other malignancy within the last 3 years (exception of in situ carcinoma, skin carcinomas,thyroid papillary carcinoma, localized prostate carcinoma Gleason 6 and in situ breast carcinoma)

14.If Pregnant patients, breastfeeding patients, and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in the protocol for the duration of the study and for at least 6 months after the last dose of cisplatin and 60 days after the last dose of avelumab

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 psychologic 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

18.Prior organ transplantation including allogenic stem-cell transplantation

19.Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (= New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.

20.Persisting toxicity related to prior therapy or pre-existing conditions (NCI CTCAE v. 4.03 Grade > 1); however, alopecia, sensory neuropathy Grade = 2, or other Grade = 2 not constituting a safety risk based on investigator’s judgment are acceptable

21.Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

22.Concurrent enrolment in another clinical trial using an investigational anti-cancer treatment within 28 days prior to the first dose of study treatment

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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