A Phase II Randomised Controlled Study Assessing the Role of Dose Escalation Using [18F] FMISO PET CT in Head and Neck Cancer: The DE-HyART (Dose Escalation Using Hypoxia-adjusted Radiotherapy) Protocol
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 124
- 试验地点
- 1
- 主要终点
- Locoregional Control (LRC)
研究概览
简要总结
DE-HyART is a phase II clinical trial aimed at understanding the effects of escalating radiation doses to hypoxic sub-volumes inherent to squamous cell head and neck cancer. The study is aimed at assessing locoregional control, feasibility, and acceptable toxicity with such a strategy.
详细描述
DE-HyART is a randomized, non-blinded study that assesses the effects of combining IMRT (using SIB-Sequential planning) with dose-escalation to hypoxic sub-volume delineated using [18-F] FMISO. The treatment protocol will also include concurrent chemotherapy with cisplatin at standard uniform dosing.
Patients with HNSCC whose cancer is determined to originate from the oral cavity, oropharynx, larynx, and hypopharynx will be selected. The included patients will be subjected to [18F] FMISO scan, labeled as baseline FMISO. Depending upon the result of the baseline FMISO, the patient will be either hypoxic or anoxic. Patients exhibiting no hypoxia in their tumor will be labeled as Arm 1 and act as an external cohort. Patients with hypoxia will be randomized (1:1) into two arms - Arms 2 and 3. Both arms will be subjected to chemoradiation by IMRT and concurrent chemotherapy with cisplatin at 40mg/m2. In Arm 3, the trial arm will receive an additional 10 Gy @ 2 Gy per fraction in phase II (total 80 Gy) to the HSV + 5mm isotropic margin.
One twenty-four patients will recruited in a 1:1 fashion between Arm 3 and Arm 2. The primary endpoint will be locoregional control and its possible increase in control.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age: 18 - 70 years
- •Willingness to sign informed consent (written/video documentation)
- •Performance status: ECOG 0 - 2
- •Histology proved - squamous cell carcinoma
- •Any grade, gender
- •Tumour sites: Oral Cavity, Oropharynx, Hypopharynx and Larynx
- •Sufficient bone marrow reserve within the last 14 days.
- •Hb: > 10g/dl (corrected)
- •TLC: > 4,000 per cumm
- •Platelet: >1.5Lakh per cumm
- •Liver functions and kidney functions within normal limits
- •Nutritional and dental assessment before inclusion into the study
排除标准
- •HPV (p16) positive tumours
- •Prior surgery and/or radiation therapy given for any HNC
- •T1/T2 Glottis
- •Metastatic disease or disease not amenable for definitive locoregional treatment.
- •Medical co-morbidity hampering the administration of radiation and/or chemotherapy (cisplatin)
- •Pregnancy or lactation
研究组 & 干预措施
Arm 3 - DE-HyART
The radiation dose will be similar to 'arm 2'. In addition, the HSV identified on baseline FMISO scans will be contoured, and an isotropic margin of 5 mm will be given. This volume will be boosted in phase II to a total dose of 80 Gy. (Addition of 30 Gy in 3 Gy daily fraction added in phase II as a simultaneous integrated boost - SIB).
干预措施: DE-HyART (Radiation)
Arm 3 - DE-HyART
The radiation dose will be similar to 'arm 2'. In addition, the HSV identified on baseline FMISO scans will be contoured, and an isotropic margin of 5 mm will be given. This volume will be boosted in phase II to a total dose of 80 Gy. (Addition of 30 Gy in 3 Gy daily fraction added in phase II as a simultaneous integrated boost - SIB).
干预措施: Cisplatin injection (Drug)
Arm 2 - Hypoxic Comparator Arm
The prescribed radiotherapy dose will be 70 Gy in 2 Gy per fraction daily. The elective volume will be treated with 50 Gy in 2 Gy per fraction daily till the first 5 weeks. The entire treatment will be delivered in a phased mannered using sequential planning.
干预措施: Standard Arm (Radiation)
Arm 2 - Hypoxic Comparator Arm
The prescribed radiotherapy dose will be 70 Gy in 2 Gy per fraction daily. The elective volume will be treated with 50 Gy in 2 Gy per fraction daily till the first 5 weeks. The entire treatment will be delivered in a phased mannered using sequential planning.
干预措施: Cisplatin injection (Drug)
Arm 1 - Non-hypoxic arm
The patients will be treated with a standard of care where the treatment will not be controlled, and these patients will act as external control representing clinical practice. However, these patients will be discussed in the head and neck multispeciality clinic and follow the institutional approach. They will be subjected to treatment similar to 'arm 2' but are allowed protocol deviation as per treating radiation oncology discretion.
干预措施: Cisplatin injection (Drug)
Arm 1 - Non-hypoxic arm
The patients will be treated with a standard of care where the treatment will not be controlled, and these patients will act as external control representing clinical practice. However, these patients will be discussed in the head and neck multispeciality clinic and follow the institutional approach. They will be subjected to treatment similar to 'arm 2' but are allowed protocol deviation as per treating radiation oncology discretion.
干预措施: Standard fractionation (Radiation Oncology preference) (Radiation)
结局指标
主要结局
Locoregional Control (LRC)
时间窗: Disease recurrence locally or analysis cut-off point. The analysis cut off pint is 24 months
LRC is defined as the absence of tumor recurrence or progression within the primary tumor site and the regional lymph nodes, as determined by clinical evaluation, imaging studies, and/or biopsy confirmation. LRC will be assessed at predefined time points, with the primary time point being 2 years post-treatment
次要结局
- Overall Survival (OS)(Death during following up or analysis cut-off point. The analysis cut off pint is 24 months)
- Locoregional Relapse Free Survival (LRFS)(Disease/Death during following up or analysis cut-off point. The analysis cut off pint is 24 months)
研究者
Munish Gairola
Dr
Rajiv Gandhi Cancer Institute & Research Center, India