Head and Neck Squamous Cell Carcinoma
Conditions
Brief summary
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.
Detailed description
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.
Interventions
RADIATIONDE-HyART
The HSV delineation will be done for patients in arm 3 using baseline FMISO. The HSV will be contoured and adjusted according to the second FMISO scan done between the 4th - the 5th week of radiation treatment. A planning CT will also be repeated at the time for adjusting the HSV to account for temporal changes. The Biological Target Volume thus generated after adequate margins will be prescribed 30 Gy in 10 fractions over and above the standard fractination.
RADIATIONStandard 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.
DRUGCisplatin injection
Concurrent chemotherapy, weekly Inj Cisplatin 40mg/m2. This will be given if clinically indicated
RADIATIONStandard fractionation (Radiation Oncology preference)
Standard institutional practice is detailed before starting the patient. Doses 66-70 Gy over 6-7 weeks
Sponsors
Varian, a Siemens Healthineers Company
Rajiv Gandhi Cancer Institute & Research Center, India
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Locoregional Control (LRC) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Locoregional Relapse Free Survival (LRFS) | Disease/Death during following up or analysis cut-off point. The analysis cut off pint is 24 months | LRFS is defined as the time from the date of randomization to the first histopathologically confirmed relapse of locoregional disease. If there is no confirmed recurrence, the LRC duration will be censored at the time of analysis. Death from any cause will be considered as an event in LRFS. |
| Overall Survival (OS) | Death during following up or analysis cut-off point. The analysis cut off pint is 24 months | The duration of OS was defined from the date of surgery to death from any cause. Therefore, if there is no death (for any reason), the OS duration will be cut-off at the analysis. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Acute toxicity | Till 6 months of finishing radiotherapy | The acute toxicity will be measured by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 |
| Patient-reported outcome QLQ-HN35 questionnaire | During treatment, at 3 month and 6 month interval of completion of radiotherapy | QLQ-H&N35 |
| Late toxicity assessment | At 1 year and 2 year follow-up | Measuring scale: (RTOG/European Organisation for the Research and Treatment of Cancer late toxicity criteria) |
| Patient-reported outcome questionnaire | During treatment, at 3 month and 6 month interval of completion of radiotherapy | EORTC QLQ-C30 |
Countries
India
Contacts
Primary ContactSarthak Tandon, DNB
Outcome results
None listed