NCT03576417进行中（未招募）3 期
A Phase III Randomized Trial of Post-operative Adjuvant Nivolumab and Concomitant Chemo-radiotherapy in High-risk Patients With Resected Squamous Cell Carcinoma of Head and Neck
Groupe Oncologie Radiotherapie Tete et Cou1 个研究点 分布在 1 个国家目标入组 680 人开始时间: 2018年10月10日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 680
- 试验地点
- 1
- 主要终点
- Disease free survival
研究概览
简要总结
The purpose of this study is to determine the efficacy of nivolumab + cisplatin-RT relative to standard of care (SOC) cisplatin-RT alone, using the disease-free survival (DFS by investigator imaging assessment) as primary endpoint )
详细描述
This open-label, randomized, controlled, multicenter phase III study will include 680 patients who have been operated for their LA SCCHN and exhibiting extra capsular extension (ECE) and/or positive margins (high risk). Subjects will be randomized (1:1) to receive post-operative concomitant cisplatin-RT with or without nivolumab.
The study is designed with the general objective of demonstrating that treatment with nivolumab in combination with 3 cycles of cisplatin during RT is more efficient and not more toxic than the SOC 3 cycles of cisplatin during RT.
Stratification will be based on the P16 status (immunohistochemistry assay on surgical sample). Two classes: Oropharyngeal Cancer (OPC) p16 positive versus OPC p16 negative or not OPC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age > 18 and < 75 years
- •Performance Status (PS) ECOG 0-1 (Appendix 2)
- •Written informed consent
- •Recording of alcohol consumption and smoking history
- •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
- •Squamous cell carcinoma of the head and neck treated by primary surgery
- •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)
- •Subject must have complete macroscopic resection.
- •Subject must be free of disease
- •Recovery from the surgical procedure allowing for cisplatin-Radiotherapy
- •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
- •Patient/tumor carrying a high risk of relapse with:
- •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.
- •Adequate tumor specimen from archived or resected tissue available for PD-L1, TILs and immune landscape and other biomarker evaluation
- •For oropharyngeal tumor, known p16 status (by IHC)
- •Patient's ability to receive cisplatin 100 mg/m2 for 3 cycles:
- •Creatinine Cclearance (CrCl) ≥ 60 mL/min (measured or calculated by Cockcroft and Gault method) or estimated Glomerular Filtration Rate (eGFR) ≥ 60 mL/min/1.73m2 (determined by CKDEPI or MDRD method). The highest value should be considered if both are assessed.
- •Absolute neutrophil count ≥1 500/mm3, platelets ≥100 000/mm3, haemoglobin ≥ 9 g/dL, aspartate transaminase (AST) and alanine transaminase (ALT) less than 2.5 times the upper limit of the normal range (ULN), total bilirubin ≤ 1.5 mg/dL(except Gilbert Syndrom: < 3.0 mg/dL).
- •Peripheral neuropathy ≤ grade 1
- •No hearing loss (assessed clinically and confirmed by audiogram if doubtful)
- •Cardiac function compatible with hyperhydration
- •No administration of prophylactic phenytoin
- •Patients aged 71-74 years,must be fit according to geriatric evaluation
排除标准
- •Nasopharyngeal, paranasal sinuses, nasal cavity tumours or thyroid cancers
- •Squamous cell carcinoma involving cervical neck nodes with unknown primary site
- •Metastatic disease
- •Incomplete macroscopic resection (R2), as stated in the surgical report
- •Known active viral infection Human Immunodeficiency Virus (HIV), Hepatitis B/C) or known history of positive test for HIV, active autoimmune disease and/or an active immunodeficiency or ongoing immunosuppressive therapy
- •Active Central Nervous System disease
- •Interstitial lung disease
- •Active infection
- •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
- •Concurrent treatment with any other systemic anti-cancer therapy that is not specified in the protocol
- •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
- •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)
- •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
- •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.
- •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
- •Known hypersensitivity to study drugs
- •Prior organ transplantation including allogenic stem-cell transplantation
- •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
- •Concurrent enrolment in another clinical trial using an investigational anti-cancer treatment within 28 days prior to the first dose of study treatment
- •Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness
- •Any psychiatric condition (including active suicidal ideation), or psychological, or familial, or sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- •Individuals deprived of liberty or placed under the authority of a tutor.
研究组 & 干预措施
RT+ cisplatin
Active Comparator
100 mg/m2 of cisplatin on days 1, 22,43 of RT
干预措施: Cisplatin (Drug)
RT+ cisplatin
Active Comparator
100 mg/m2 of cisplatin on days 1, 22,43 of RT
干预措施: RT (Radiation)
RT+ cisplatin + nivolumab
Experimental
- 240 mg of nivolumab 3 weeks before RT-Cisplatin
- 360 mg of nivolumab on days 1, 22,43 of -RT-cisplatin
- 480 mg of nivolumab for maintenance
干预措施: Cisplatin (Drug)
RT+ cisplatin + nivolumab
Experimental
- 240 mg of nivolumab 3 weeks before RT-Cisplatin
- 360 mg of nivolumab on days 1, 22,43 of -RT-cisplatin
- 480 mg of nivolumab for maintenance
干预措施: Nivolumab (Drug)
RT+ cisplatin + nivolumab
Experimental
- 240 mg of nivolumab 3 weeks before RT-Cisplatin
- 360 mg of nivolumab on days 1, 22,43 of -RT-cisplatin
- 480 mg of nivolumab for maintenance
干预措施: RT (Radiation)
结局指标
主要结局
Disease free survival
时间窗: 3 years after the end of RT
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.
次要结局
- Overall survival(60 months after the end of treatment)
- Acute toxicity(During treatment and until 90 months after the end of RT)
- Late toxicity(1 to 5 years after radiotherapy)
研究者
研究点 (1)
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