A Pilot Study of Ultra-High Dose Rate (ConformalFLASH®), for Reirradiation of Carcinoma of the Head and Neck

Overview

This pilot study is designed to evaluate the feasibility of delivering ultra-high dose-rate conformal proton therapy (ConformalFLASH) in participants requiring re-irradiation for head and neck cancer who are not amenable to surgical resection. ConformalFLASH treatment planning and delivery workflows are comparable to those of conventional Stereotactic Body Radiation Therapy (SBRT), a standard approach for re-irradiation in this population.

Detailed description

C-FLASH-01 is a pilot study evaluating the feasibility of delivering ultra-high dose-rate conformal proton therapy (ConformalFLASH) to participants requiring re-irradiation for head and neck cancer who are not amenable to surgical resection. Stereotactic Body Radiation Therapy (SBRT) re-irradiation is a standard approach that enables highly conformal dose delivery over a limited number of fractions. ConformalFLASH is an investigational approach that applies SBRT principles using proton therapy delivered at ultra-high dose rates (≥ 40 Gray Relative Biological Effectiveness (GyRBE)/second), with the potential to reduce normal tissue toxicity while maintaining tumor control. Participants will undergo treatment planning and delivery consistent with standard SBRT workflows. Treatment consists of five fractions (8 GyRBE per fraction) delivered over approximately 1.5 to 2 weeks. The primary objective is to assess the feasibility of delivering conformal proton SBRT at dose rates ≥ 40 GyRBE/second, along with evaluation of acute toxicity. Secondary objectives include assessment of treatment delivery accuracy, late toxicity, clinical outcomes, and patient-reported quality of life.

Interventions

• Radiation ConformalFLASH irradiation
  Subjects will be treated with SBRT (8 GyRBE x 5 fractions over 1.5-2 weeks), using pencil-beam scanning proton therapy, delivered at an average dose rate of ≥ 40 GyRBE/second, without chemotherapy.

Primary outcome measures

• ConformalFLASH treatment delivery feasibility [Time frame: Through treatment completion (within 1 month after last fraction)]
• Acute toxicities [Time frame: Up to 3 months after treatment start]

Secondary outcome measures (7)

• ConformalFLASH treatment delivery accuracy [Time frame: Through treatment completion (within 1 month after last fraction)]
• Late toxicities [Time frame: Beyond 3 months after start of treatment and up to 5 years]
• Local Control [Time frame: 3 months and 1 year]
• Regional control [Time frame: 3 months and 1 year]
• Metastasis-free survival [Time frame: 3 months and 1 year]
• Overall survival [Time frame: 3 months and 1 year]
• Patient-reported quality of life [Time frame: Up to 5 years]

Eligibility criteria

Inclusion criteria

• Patients must sign an informed consent document that indicates they are aware of the investigational nature of the treatment in this protocol as well as the potential risks and benefits
• Patients ≥ 18 years old
• Patients ineligible for or decline upfront surgical resection
• Histologically confirmed diagnosis of carcinoma of the head and neck
• Prior receipt of at least 45 GyRBE radiotherapy to the head and neck
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 or evidence of similar in the electronic medical record
• Life expectancy of more than 12 weeks
• Ability to understand and the willingness to provide written informed consent and to follow the study procedures

Exclusion criteria

• Receipt of prior head and neck radiotherapy within the prior 6 months
• Surgical resection of the current disease in the head and neck
• More than 3 areas of disease requiring reirradiation
• Disease focus exceeding 6.5 cm in greatest dimension
• Presence of distant metastatic disease
• Involvement of any of the following structures: skin, carotid artery, or mandible
• Receipt of concurrent chemotherapy during radiotherapy
• Uncontrolled intercurrent illness including medical and psychiatric, and social situations that would limit compliance with study requirements
• Enrolled in any other investigational studies that involve administrations of another cancer therapeutic (such as surgery, chemotherapy, immunotherapy) during RT
• Pregnant and/or breastfeeding

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• The University of Pennsylvania, Department of Radiation Oncology — Philadelphia

Publications

• Vargo JA, Ferris RL, Ohr J, Clump DA, Davis KS, Duvvuri U, Kim S, Johnson JT, Bauman JE, Gibson MK, Branstetter BF, Heron DE. A prospective phase 2 trial of reirradiation with stereotactic body radiation therapy plus cetuximab in patients with previously irradiated recurrent squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys. 2015 Mar 1;91(3):480-8. doi: 10.1016/j.ijrobp.20 PMID 25680594
• Heron DE, Ferris RL, Karamouzis M, Andrade RS, Deeb EL, Burton S, Gooding WE, Branstetter BF, Mountz JM, Johnson JT, Argiris A, Grandis JR, Lai SY. Stereotactic body radiotherapy for recurrent squamous cell carcinoma of the head and neck: results of a phase I dose-escalation trial. Int J Radiat Oncol Biol Phys. 2009 Dec 1;75(5):1493-500. doi: 10.1016/j.ijrobp.2008.12.075. Epub 2009 May 21. PMID 19464819
• Lartigau EF, Tresch E, Thariat J, Graff P, Coche-Dequeant B, Benezery K, Schiappacasse L, Degardin M, Bondiau PY, Peiffert D, Lefebvre JL, Lacornerie T, Kramar A. Multi institutional phase II study of concomitant stereotactic reirradiation and cetuximab for recurrent head and neck cancer. Radiother Oncol. 2013 Nov;109(2):281-5. doi: 10.1016/j.radonc.2013.08.012. Epub 2013 Nov 18. PMID 24262821

Identifiers

NCT: NCT07644585 · IBA-04-UP

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗