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

January 16, 2025 updated by: Munish Gairola, Rajiv Gandhi Cancer Institute & Research Center, India

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

124

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • India
      • Delhi, India, 110085
        • Recruiting
        • Rajiv Gandhi Cancer Institute and Research Centre
        • Contact:
        • Principal Investigator:
          • Munish Gairola, MD, DNB Radiation Oncology
        • Sub-Investigator:
          • Sarthak Tandon, DNB Radiation Oncology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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).
Radiation: DE-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.
Other Names:
  • FMISO
  • Dose escalated radiotherapy
  • Hypoxic sub volume
Drug: Cisplatin injection
Concurrent chemotherapy, weekly Inj Cisplatin 40mg/m2. This will be given if clinically indicated
Active Comparator: 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.
Drug: Cisplatin injection
Concurrent chemotherapy, weekly Inj Cisplatin 40mg/m2. This will be given if clinically indicated
Radiation: Standard 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.
Other Names:
  • Standard Sequential fractionation without dose escalation
Placebo Comparator: 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.
Drug: Cisplatin injection
Concurrent chemotherapy, weekly Inj Cisplatin 40mg/m2. This will be given if clinically indicated
Radiation: Standard fractionation (Radiation Oncology preference)
Standard institutional practice is detailed before starting the patient. Doses 66-70 Gy over 6-7 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Locoregional Control (LRC)
Time Frame: 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
Disease recurrence locally or analysis cut-off point. The analysis cut off pint is 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: 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.
Death during following up or analysis cut-off point. The analysis cut off pint is 24 months
Locoregional Relapse Free Survival (LRFS)
Time Frame: 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.
Disease/Death during following up or analysis cut-off point. The analysis cut off pint is 24 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acute toxicity
Time Frame: Till 6 months of finishing radiotherapy
The acute toxicity will be measured by Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Till 6 months of finishing radiotherapy
Late toxicity assessment
Time Frame: At 1 year and 2 year follow-up
Measuring scale: (RTOG/European Organisation for the Research and Treatment of Cancer late toxicity criteria)
At 1 year and 2 year follow-up
Patient-reported outcome questionnaire
Time Frame: During treatment, at 3 month and 6 month interval of completion of radiotherapy
EORTC QLQ-C30
During treatment, at 3 month and 6 month interval of completion of radiotherapy
Patient-reported outcome QLQ-HN35 questionnaire
Time Frame: During treatment, at 3 month and 6 month interval of completion of radiotherapy
QLQ-H&N35
During treatment, at 3 month and 6 month interval of completion of radiotherapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rajiv Gandhi Cancer Institute & Research Center, India

Collaborators

Varian, a Siemens Healthineers Company

Investigators

  • Principal Investigator: Munish Gairola, MD,DNB Radiation Oncology, Rajiv Gandhi Cancer Institute and Research Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 8, 2024

Primary Completion (Estimated)

April 1, 2028

Study Completion (Estimated)

April 1, 2028

Study Registration Dates

First Submitted

September 18, 2023

First Submitted That Met QC Criteria

October 11, 2023

First Posted (Actual)

October 18, 2023

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 16, 2025

Last Verified

January 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Res/SCM/58/2023/33

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

data privacy issues with the country laws before any commitment

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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