A Phase I/II Study of Olaparib in Addition to Cisplatin Based Concurrent Chemoradiotherapy for Patients With High Risk Locally Advanced Squamous Cell Carcinoma of the Head and Neck (HNSCC)
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Frequency of dose limiting toxicities
研究概览
简要总结
The aim of this study is to find the safe dose and best dosing schedule of olaparib to give in combination with cisplatin based chemoradiotherapy (CRT) in patients with locally advanced head and neck cancer. The dose decided on in this part of the study will become the recommended dose for the randomised Phase II trial.
详细描述
This is a dose escalating Phase I/II trial evaluating the safety and tolerability of the addition of olaparib to CRT in high risk locally advanced human papillomavirus (HPV) negative Squamous Cell Carcinoma of the Head and Neck (HNSCC). A fixed dose of weekly cisplatin and intensity-modulated radiation therapy (IMRT) will be used, with doses of olaparib escalating for consecutive days and both dose level and duration will be increased through each cohort.
This Phase I trial will assess how olaparib, a poly ADP ribose polymerase (PARP) inhibitor is tolerated when added to standard chemoradiotherapy treatment.
Patients will be recruited from sites in the UK only.
A placebo controlled, randomised Phase II trial will follow once the recommended dose and schedule of olaparib has been established.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed high risk, locally advanced HNSCC patients (TNM staging: T-any N2/3 M0, bulky T3 or T4 N-any M0) who would normally be offered cisplatin-based radical chemoradiotherapy
- •Estimated life expectancy of at least 12 weeks
- •WHO performance status of 0 or 1
- •Aged ≥18 years of age
- •Adequate major organ function
- •Willing to use contraception for the duration of the trial treatment and for six months after completion of treatment
- •Able to give informed consent
- •Willing and able to comply with the protocol for the duration of the study
排除标准
- •Head & neck cancers of the following types:
- •Nasopharyngeal and paranasal sinus tumours,
- •Oral squamous cell carcinomas (tumours of the oral cavity),
- •Human Papilloma Virus positive oropharyngeal tumours (tonsillar and tongue base tumours)
- •Confirmed distant metastatic disease
- •Previous chemotherapy or radiotherapy for the treatment of HNSCC tumour
- •Previous therapy with a PARP inhibitor
- •Pre-existing gastrointestinal disorders that may interfere with the delivery or absorption of olaparib
- •Grade 3 or 4 peripheral neuropathy
- •Significant hearing difficulties or tinnitus (deaf patients can be included)
- •The current use of drugs which are known to inhibit or induce CYP3A4
研究组 & 干预措施
single arm
All patients will receive induction chemotherapy (cisplatin and 5-FU), followed by cisplatin chemotherapy and radiotherapy in addition to oral olaparib.
Induction chemotherapy (21 day cycle)
- Drug: cisplatin 80mg/m2 (day 1)
- Drug: 5-FU (fluorouracil) 1000mg/m2/day (day 1-4 continuous infusion)
olaparib plus chemoradiotherapy (8 weeks)
- Drug: olaparib
- Drug: Cisplatin
- Radiation
干预措施: olaparib (Drug)
single arm
All patients will receive induction chemotherapy (cisplatin and 5-FU), followed by cisplatin chemotherapy and radiotherapy in addition to oral olaparib.
Induction chemotherapy (21 day cycle)
- Drug: cisplatin 80mg/m2 (day 1)
- Drug: 5-FU (fluorouracil) 1000mg/m2/day (day 1-4 continuous infusion)
olaparib plus chemoradiotherapy (8 weeks)
- Drug: olaparib
- Drug: Cisplatin
- Radiation
干预措施: cisplatin (Drug)
single arm
All patients will receive induction chemotherapy (cisplatin and 5-FU), followed by cisplatin chemotherapy and radiotherapy in addition to oral olaparib.
Induction chemotherapy (21 day cycle)
- Drug: cisplatin 80mg/m2 (day 1)
- Drug: 5-FU (fluorouracil) 1000mg/m2/day (day 1-4 continuous infusion)
olaparib plus chemoradiotherapy (8 weeks)
- Drug: olaparib
- Drug: Cisplatin
- Radiation
干预措施: Intensity Modulated Radiotherapy (Radiation)
结局指标
主要结局
Frequency of dose limiting toxicities
时间窗: 6 weeks post completion of treatment
次要结局
- Complete response rate(12 weeks post completion of treatment)
- Time to loco-regional progression(2 years post completion of treatment)