Dose Escalation Using Hypoxia-adjusted Radiotherapy (DE-HyART)

Rajiv Gandhi Cancer Institute & Research Center, India

Status and phase: Enrolling; Phase 2

Conditions: Head and Neck Squamous Cell Carcinoma

Treatments: Radiation: DE-HyART; Radiation: Standard Arm; Radiation: Standard fractionation (Radiation Oncology preference); Drug: Cisplatin injection

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT06087614

Res/SCM/58/2023/33

Details and patient eligibility

About

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.

Full 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.

Enrollment: 124 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

124 participants in 3 patient groups, including a placebo group

Arm 3 - DE-HyART

Experimental group

Description:

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).

Treatment:

Drug: Cisplatin injection

Radiation: DE-HyART

Arm 2 - Hypoxic Comparator Arm

Active Comparator group

Description:

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.

Treatment:

Drug: Cisplatin injection

Radiation: Standard Arm

Arm 1 - Non-hypoxic arm

Placebo Comparator group

Description:

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.

Treatment:

Drug: Cisplatin injection

Radiation: Standard fractionation (Radiation Oncology preference)