Randomized trial evaluating the addition of nivolumab to cisplatin-radiotherapy combination for treatment of cancers of the head and neck

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Groupe Oncologie Radiotherapie Tete Cou

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

10 Aug 2018 → ongoing

Decision date (initial)

2024-07-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-513206-65-00

EudraCT number

2017-004936-13

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

To determine the efficacy of nivolumab + cisplatin-RT relative to SOC cisplatin-RT alone, using the disease-free survival (DFS by investigator imaging assessment) as primary endpoint

Secondary objectives 5

1. To compare the OS, local regional control, distant metastases of nivolumab in combination with cisplatin-RT vs SOC cisplatin-RT alone.
2. To determine DFS by blinded independent central imaging review
3. To evaluate the overall safety and tolerability profile of nivolumab in combination with cisplatin-RT vs SOC cisplatin-RT.
4. To evaluate DFS by PDL-1 expression (using 28-8 assay)
5. To evaluate candidate immune-related predictive biomarkers of sensitivity to nivolumab in tumor samples obtained at surgery 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.

Conditions and MedDRA coding

resected squamous cell carcinoma of head and neck

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Age > 18 and < 75 years
2. Recovery from the surgical procedure allowing for cisplatin-Radiotherapy
3. Radiotherapy planned to start within 4 to 9 weeks after surgery. However, a maximum of 1 additional week could be considered in case of delay due to healing or logistical problem
4. Patient/tumor carrying a high risk of relapse with one or more following criteria: · Extra-capsular extension (ECE) · Multiple peri-neural invasion · Multiple nodal extension without ECE (≥ 4 nodes) · Positive margins (R1 or close margin ≤ 1 mm) R1 is microscopic residual disease and close margin is R0 with a minimum margin ≤ 1 mm in any direction.
5. Adequate tumor specimen from archived or resected tissue available for PD-L1, TILs and immune landscape and other biomarker evaluation
6. Performance Status (PS) ECOG 0-1
7. Written informed consent
8. Recording of alcohol consumption and smoking history
9. Histologically proven squamous cell carcinoma of the head and neck from one or more of the following primary sites: oral cavity, oropharynx, hypopharynx or larynx
10. Squamous cell carcinoma of the head and neck treated by primary surgery
11. Histopathological classification: pStage III or IV. However, Oropharyngeal Cancer pStage II p16 positive with pT3N1 or pT4N1 and tobacco consumption ≥20 packs/year are eligible. (American Joint Committee on Cancer 8th edition)
12. Subject must have complete macroscopic resection.
13. Subject must be free of disease

Exclusion criteria 16

1. Nasopharyngeal, paranasal sinuses, nasal cavity tumours or thyroid cancers
2. Concurrent treatment with any other systemic anti-cancer therapy that is not specified in the protocol
3. Concomitant treatment with any drug on the prohibited medication list such as live vaccines. Live vaccines administered more than 30 days before study entry are permitted
4. History of other malignancy within the last 3 years (exception of in situ carcinoma, thyroid papillary carcinoma, skin carcinomas, localized prostate carcinoma Gleason 6 and in situ breast carcinoma)
5. Pregnant, 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 5 months after the last dose of nivolumab
6. Male patients who are unwilling or unable to use contraception methods for the duration of the study and for at least 6 months after the last dose of cisplatin.
7. Severe acute or chronic medical conditions including colitis, pneumonitis, pulmonary fibrosis, laboratory abnormalities or other 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
8. Any prior treatment for the current head and neck cancer other than primary surgery. This will include but is not limited to: prior tyrosine kinase inhibitors, any monoclonal antibody, induction chemotherapy, prior RT, or use of any investigational agent
9. Clinically significant (i.e., active) cardiovascular disease: · Cerebral vascular accident/stroke (< 6 months prior to enrollment) or · Myocardial infarction (< 6 months prior to enrollment) or · unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II) or · Serious cardiac arrhythmia requiring medication
10. Incomplete macroscopic resection (R2), as stated in the surgical report
11. Squamous cell carcinoma involving cervical neck nodes with unknown primary site
12. Active central nervous system disease
13. Interstitial lung disease
14. Active infection
15. Metastatic disease
16. Known active viral infection (Human Immunodeficiency Virus (HIV), Hepatitis B/C) or known history of positive test for HIV, active autoimmune disease and/or active immunodeficiency or ongoing immunosuppressive therapy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Disease free survival (DFS by investigator imaging assessments) defined as the time between the date of randomization and the date of first loco-regional or distant recurrence or death (of any cause) whichever occurs first,..

Secondary endpoints 7

1. Overall survival
2. DFS by blinded independent central imaging review
3. DFS and OS by PDL-1 status
4. Cumulative incidence of locoregional failure, cumulative incidence of distant metastatic failure and cumulative incidence of death without previous progression
5. Incidence of second primary malignancy (SCC to a distance >= 3 cm from the tumor bed and that will clearly not be attributable to a relapse or a second cancer arising outside the upper aero digestive track).
6. Safety: Adverse events and laboratory abnormalities as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v5.0). Incidence of delayed toxicity of radiotherapy (e.g. dysphagia, chronic swallowing dysfunctions, speech problems, cervical fibrosis, rate and duration of the use of feeding tubes).
7. Correlation between the immune landscape and patients’ outcome

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Groupe Oncologie Radiotherapie Tete Cou

Sponsor organisation

Groupe Oncologie Radiotherapie Tete Cou

Address

4 B Rue Emile Zola

City

Tours

Postcode

37000

Country

France

Scientific contact point

Organisation

Groupe Oncologie Radiotherapie Tete Cou

Contact name

Yun Gan TAO

Public contact point

Organisation

Groupe Oncologie Radiotherapie Tete Cou

Contact name

Mahasti Bert

Locations

5 EU/EEA countries · 81 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications