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

• Register: EUCTR
• Last refreshed on: 2 October 2017
• Main ID: EUCTR2016-004383-19-FR
• Date of registration: 08/09/2017
• Prospective Registration: No
• Primary sponsor: GORTEC
• Public title: Randomized trial of avelumab-cetuximab-Radiotherapy versus standards of care in the head and neck cancers
• Scientific 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 - REACH
• Date of first enrolment: 07/09/2017
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-004383-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: yes Other specify the comparator: Cetuximab cisplatin radiotherapy Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

France, Monaco, Switzerland

Contacts

• Name: Cécile MICHEL
• Affiliation: GORTEC

• Name: Cécile MICHEL
• Affiliation: GORTEC

Key inclusion & exclusion criteria

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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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
MedDRA version: 20.0 Level: PT Classification code 10060121 Term: Squamous cell carcinoma of head and neck System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: Avelumab
Pharmaceutical Form: Infusion

Trade Name: ERBITUX
Product Name: cetuximab
Pharmaceutical Form: Solution for injection/infusion

Trade Name: CISPLATINE MYLAN
Product Name: cisplatine
Pharmaceutical Form: Solution for infusion

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Between randomization and the first event among progression (per modified Response Evaluation Criteria in Solid Tumors version (v)1.1 and death, whatever the cause of death

Main Objective: To demonstrate that treatment with avelumab in combination with cetuximab-RT is superior to SOC Cisplatin-RT and/or to SOC cetuximab-RT alone in terms of PFS in front-line patients with locally advanced SCCHN. Each cohort will be analyzed separately.

Primary end point(s): Progression Free Survival

Secondary Objective: To evaluate the overall safety and tolerability profile of avelumab in combination with cetuximab-RT as compared to SOC cisplatin-RT or cetuximab-RT alone.
To evaluate the effect of avelumab in combination with cetuximab-RT compared to SOC CT-RT or cetuximab-RT alone on health-related quality of life.
To evaluate candidate immune-related predictive biomarkers of sensitivity or insensitivity to treatment with avelumab in pre-treatment tumor samples and in blood (levels of cells, DNA, RNA, or proteins that may be related to antitumor immune response and/or disease progression) and to explore potential correlations between treatment outcome and the immune landscape / TCR sequencing / antitumor cellular responses

Secondary Outcome(s)

Secondary end point(s): Overall survival
Cumulative incidence of locoregional failure, cumulative incidence of distant metastatic failure by Investigator assessment and cumulative incidence of death without previous progression
Safety: Acute adverse events and laboratory abnormalities as graded by National Cancer Institute Common Terminology Criteria for Adverse Events , v4.03. Incidence of delayed toxicity
Patient-Reported Outcomes: Health related quality of life assessed by EORTC QLQ-C30 and H&N35 questionnaires

Timepoint(s) of evaluation of this end point: Overall survival
Cumulative incidence of locoregional failure, cumulative incidence of distant metastatic failure by Investigator assessment and cumulative incidence of death without previous progression
Safety: Acute adverse events and laboratory abnormalities as graded by National Cancer Institute Common Terminology Criteria for Adverse Events , v4.03. Incidence of delayed toxicity
Patient-Reported Outcomes: Health related quality of life assessed by EORTC QLQ-C30 and H&N35 questionnaires

Secondary ID(s)

GORTEC_2017-01

NCT02999087

Source(s) of Monetary Support

GORTEC

MERCK GROUP