Combined Hypofractionated Stereotactic Body Radiotherapy With Immunomodulating Systemic Therapy for Inoperable Recurrent Head and Neck Cancer: Detection of the Maximum Tolerated Dose.
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 4
- 主要终点
- maximum tolerated dose
研究概览
简要总结
To derive the maximum tolerated dose of hypofractionated stereotactic body radiotherapy (SBRT) using dose painting by numbers with immunomodulating systemic therapy in patients that are reirradiated for recurrent squamous cell carcinoma of the head and neck.
详细描述
The standard treatment in inoperable locally or regionally recurrent head and neck cancer has long been palliative systemic therapy using the so-called EXTREME-scheme: a combination of cisplatin, 5-fluorouracil and cetuximab. This therapy remains without realistic chances of cure. More recently, immunotherapy using nivolumab has demonstrated to result in long-term disease control of 1-2 year in cisplatin-refractory recurrent or metastatic head and neck cancer, however only in a small portion of patients (13%).
Fractionated high-dose local or regional re-irradiation is mostly given in a 6-7 weeks scheme. Using stereotactic body radiotherapy (SBRT), high radiotherapy doses can be given in a short time span. Severe late adverse events have been reported using SBRT but seem less frequent than in patients re-treated with conventional schedules. A possible solution to be able to administer higher doses is combining SBRT with dose painting, thus giving these high doses on small subvolumes only.
Addition of concomitant therapy to reirradiation may further improve outcomes due to radiosensitization and direct cytotoxicity. Therefore the investigator aims to combine high doses with concomitant therapy in the proposed study.
The immunomodulatory effect caused by radiation has been demonstrated both in animal models and clinical trials and leads to an enhanced local control as well as to eradication of distant metastasis. This so-called abscopal effect is reached through a systemic immune response evoked by the release of damage-associated molecular patterns (DAMPs) by the dying tumor-cells, also called immunogenic cell death (ICD).
The investigator hypothesizes that an abscopal effect could be present for patients presenting locoregional recurrent disease with asymptomatic distant metastases, thereby offering at least symptom control at the primary site while palliative systemic treatment could be postponed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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 local, regional or combined locoregional recurrence of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx or cancer of unknown primary (CUP) in the neck in previously irradiated tissue, with former irradiation with curative intent.
- •Patients with non-symptomatic distant metastases and local, regional or combined locoregional recurrence can be included.
- •In case of non-metastatic disease, the recurrence must be primarily unresectable recurrence and/or patients refused surgery.
- •Time interval 6-24 months after the end of the initial radio(chemo)therapy for primary head and neck cancer.
- •Decision of the Head and Neck Tumor Boards at the recruiting centre to offer salvage radio(chemo)therapy, palliative chemotherapy or anti-PD-1 antibody treatment with nivolumab for cisplatin-refractory locoregional recurrent head and neck squamous cell carcinoma.
- •Karnofsky performance status ≥
- •Age ≥ 18 years old.
- •Informed consent obtained, signed and dated before specific protocol procedures.
排除标准
- •Previous radiotherapy was for cT1-2 cN0 M0 glottic cancer.
- •Grade ≥ 4 late toxicity after the initial radio(chemo)therapy.
- •Brachytherapy as treatment for second primary / recurrence.
- •Previous (combination with) immunotherapy for the primary or the recurrent squamous cell carcinoma.
- •Impossibility of oral intake of cyclophosphamide.
- •For patients receiving cyclophosphamide: necessary intake during therapy of allopurinol, amiodarone, digoxin, hydrochlorothiazide, indomethacin, phenobarbital, phenytoin, warfarin. clopidogrel, ticlopidine, carbamazepine, efavirenz, rifampicin, ritonavir
- •High risk for arterial blow-out: 1 of following criteria is sufficient to exclude patients:
- •soft tissue necrosis
- •skin invasion of the recurrent cancer
- •circumferential involvement of > 180° of a carotid artery
- •Symptomatic distant metastases.
- •Other uncontrolled second primary tumors.
- •Pregnant or lactating women.
- •Mental condition rendering the patient unable to understand the nature, scope, and possible consequences of the study.
- •Patient unlikely to comply with protocol, i.e. uncooperative attitude, inability to return for follow-up visits, and unlikely to complete the study.
结局指标
主要结局
maximum tolerated dose
时间窗: 3 months after radiotherapy
maximum tolerated dose of hypofractionated stereotactic body radiotherapy (SBRT) using dose painting by numbers with immunomodulating systemic therapy in patients that are reirradiated for recurrent squamous cell carcinoma of the head and neck
次要结局
- symptom palliation - dysphagia(through study completion, an average of 12 months)
- grade ≥ 3 toxicity-free survival(through study completion, an average of 12 months)
- immune response(using serum taken before treatment and at each fraction of SBRT, at weeks 6-14)
- local control(3 months after SBRT and thereafter through study completion, an average of 12 months)
- Progression free survival(through study completion, an average of 12 months)
- symptom palliation - pain(through study completion, an average of 12 months)
- Overall survival(through study completion, an average of 12 months)
- QOL - general(before therapy, week 3, week 6, week 10, week 14)
- QOL - H&N specific(before therapy, week 3, week 6, week 10, week 14)
- topographic distribution of recurrence(through study completion, an average of 12 months)
- time to further treatment(through study completion, an average of 12 months)
研究者
Radiotherapie
Principal Investigator
University Hospital, Ghent