A Phase II Randomized Study to Determine the Tolerance and Efficacy of Pembrolizumab or Cetuximab Combined With Radiation Therapy in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 133
- 试验地点
- 1
- 主要终点
- Locoregional Control
研究概览
简要总结
The general aim of the study is to evaluate the anti-tumour activity and the tolerance profile of Pembrolizumab + RT in comparison to cetuximab + RT in patients with locally advanced HNSCC and to explore potential correlations between treatment outcome and the immune landscape.
详细描述
A majority of HNSCC are locally advanced and commonly treated with concomitant chemo-radiotherapy (CT-RT). However, a large proportion of patients with locally advanced stage are not suitable for receiving cisplatinum-based chemotherapy (CT) concomitant with radiotherapy (RT) either due to age, general and/or medical condition(s).
An alternative standard treatment has been established, combining RT and cetuximab.
However, both CT-RT and cetuximab-RT which are considered as standard approaches in locally advanced non operated HNSCC are associated with poor outcome in patients with the most advanced T stage (T4) and/or N stage (>=N2) and/or HPV negative tumours. A new and promising approach could target immune response.
Pembrolizumab is a high-affinity monoclonal anti-PD1 antibody which showed antitumor activity in melanoma and NSCLC. In the KEYNOTE-012 (multi-center, nonrandomized Phase Ib HNSCC), Pembrolizumab was well tolerated and safe with no serious drug related AEs reported. About 51% (26/51) of patients had decreased tumor burden which was seen both in HPV (-) and HPV(+) HNSCC.
This observation led to the hypothesis generated in the current study that Pembrolizumab is potentially a very active drug in HNSCC and that the combination of Pembrolizumab with radiotherapy will be well tolerated, given the very good toxicity profile of the drug and will improve the outcome of patients with locally advanced HNSCC non suitable for CT-RT, as compared to the treatment of reference combining cetuximab and RT.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent
- •Age ≥18 ≤ 80 years.
- •Performance Status ECOG 0-1
- •Histologically confirmed diagnosis of previously untreated locally advanced HNSCC (Stage III, IVa and IVb according to the American Joint Committee on Cancer Staging System) of one or more of the following sites: oral cavity, oropharynx, hypopharynx and larynx
- •Availability of pre-treatment tumour tissue (for biomarker analysis, PD -L1, TILs and immune-monitoring)
- •p16 expression from tumor sample (immunohistochemistry)
- •Recording of the smoking history
- •No viral infection (HIV, Hepatitis B/C)
- •No autoimmune disease
- •No immunodeficiency or immunosuppressive therapy
- •No active CNS disease
- •No interstitial lung disease
- •No active infection
- •Women of child-bearing potential: negative serum pregnancy test at screening and use of appropriate contraception methods from study entry
- •Patients not proposed cisplatin-based chemotherapy because of age, general condition, if medically unfit or patient refusal.
- •Adequate organ laboratory values
- •Health insurance coverage
排除标准
- •Nasopharyngeal, paranasal sinuses, nasal cavity tumours or thyroid cancers;
- •Squamous cell cancer involving cervical neck nodes with unknown primary site;
- •Metastatic disease;
- •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, prior neoadjuvant therapy, prior surgical resection, or use of any investigational agent;
- •Weight loss of >10% during the last 3 weeks prior the screening visit;
- •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 (for details, see the protocol);
- •History of another malignancy within the last 3 years (exception of in situ carcinoma and skin carcinomas);
- •If female, pregnant or lactating;
- •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 reaction to study medication;
- •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.
研究组 & 干预措施
Pembrolizumab and radiotherapy
200 mg IV infusion every 3 weeks, i.e. on day 1, 22, 43 during the course of radiotherapy
干预措施: Pembrolizumab (Drug)
Pembrolizumab and radiotherapy
200 mg IV infusion every 3 weeks, i.e. on day 1, 22, 43 during the course of radiotherapy
干预措施: Radiotherapy (Radiation)
Cetuximab and radiotherapy
Loading dose of 400 mg/m² IV on Day-8, followed by weekly dose of 250 mg/m² IV during the whole course of radiotherapy.
干预措施: Cetuximab (Drug)
Cetuximab and radiotherapy
Loading dose of 400 mg/m² IV on Day-8, followed by weekly dose of 250 mg/m² IV during the whole course of radiotherapy.
干预措施: Radiotherapy (Radiation)
结局指标
主要结局
Locoregional Control
时间窗: 15 months from the end of radiation therapy
To compare between the 2 arms the rate of patients achieving Locoregional Control (LRC) at 15 months from the end of radiation therapy
次要结局
- Progression free survival(At 24 months after treatment initiation)
- Overall survival(At 24 months after treatment initiation)
- Acute adverse events(At 24 months after treatment initiation)
- Locoregional progression and distant metastasis(At 24 months after treatment initiation)
- Delayed toxicity According to RTOG late toxicity scale(At 24 months after treatment initiation)
- Duration of the feeding tube dependence(At 24 months after treatment initiation)
- Compliance to Pembrolizumab and Cetuximab(At 24 months after treatment initiation)
- Health related quality of life (QL)(At 24 months after treatment initiation)
- Impact of p16 / HPV tumor status on the efficacy of the 2 regimens in patients with oropharyngeal initial tumor(At 24 months after treatment initiation)