Dose Escalation Using Hypoxia-adjusted Radiotherapy

NCT ID: NCT06087614

Last Updated: 2025-01-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

124 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-04-08

Study Completion Date

2028-04-30

Brief Summary

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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

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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.

Conditions

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Head and Neck Squamous Cell Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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).

Group Type EXPERIMENTAL

DE-HyART

Intervention Type RADIATION

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.

Cisplatin injection

Intervention Type DRUG

Concurrent chemotherapy, weekly Inj Cisplatin 40mg/m2. This will be given if clinically indicated

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.

Group Type ACTIVE_COMPARATOR

Standard Arm

Intervention Type RADIATION

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.

Cisplatin injection

Intervention Type DRUG

Concurrent chemotherapy, weekly Inj Cisplatin 40mg/m2. This will be given if clinically indicated

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.

Group Type PLACEBO_COMPARATOR

Cisplatin injection

Intervention Type DRUG

Concurrent chemotherapy, weekly Inj Cisplatin 40mg/m2. This will be given if clinically indicated

Standard fractionation (Radiation Oncology preference)

Intervention Type RADIATION

Standard institutional practice is detailed before starting the patient. Doses 66-70 Gy over 6-7 weeks

Interventions

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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.

Intervention Type 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.

Intervention Type RADIATION

Cisplatin injection

Concurrent chemotherapy, weekly Inj Cisplatin 40mg/m2. This will be given if clinically indicated

Intervention Type DRUG

Standard fractionation (Radiation Oncology preference)

Standard institutional practice is detailed before starting the patient. Doses 66-70 Gy over 6-7 weeks

Intervention Type RADIATION

Other Intervention Names

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Dose escalated radiotherapy Hypoxic sub volume FMISO Standard Sequential fractionation without dose escalation

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Varian, a Siemens Healthineers Company

INDUSTRY

Sponsor Role collaborator

Rajiv Gandhi Cancer Institute & Research Center, India

OTHER

Sponsor Role lead

Responsible Party

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Munish Gairola

Dr

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Munish Gairola, MD,DNB Radiation Oncology

Role: PRINCIPAL_INVESTIGATOR

Rajiv Gandhi Cancer Institute and Research Centre

Locations

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Rajiv Gandhi Cancer Institute and Research Centre

Delhi, , India

Site Status RECRUITING

Countries

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India

Central Contacts

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Sarthak Tandon, DNB

Role: CONTACT

+911147022009

Facility Contacts

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Sarthak Tandon, DNB Radiation Oncology

Role: primary

(+91)11-47022009

References

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Reference Type DERIVED
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Other Identifiers

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Res/SCM/58/2023/33

Identifier Type: -

Identifier Source: org_study_id

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