A Pilot Study of Ultra-High Dose Rate (ConformalFLASH®), for Reirradiation of Carcinoma of the Head and Neck (C-FLASH-01)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Radiation: ConformalFLASH irradiation

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.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sophie Le Bail; Phone Number: +32 470 226 032; Email: sophie.lebail@iba-group.com
• Study Contact Backup: Name: Sofie Gillis; Phone Number: +32 499 985 686; Email: sofie.Gillis@iba-group.com

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The University of Pennsylvania, Department of Radiation Oncology
      • Contact: Alexander Lin, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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
2. Patients ≥ 18 years old
3. Patients ineligible for or decline upfront surgical resection
4. Histologically confirmed diagnosis of carcinoma of the head and neck
5. Prior receipt of at least 45 GyRBE radiotherapy to the head and neck
6. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 or evidence of similar in the electronic medical record
7. Life expectancy of more than 12 weeks
8. Ability to understand and the willingness to provide written informed consent and to follow the study procedures

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm; ConformalFLASH irradiation	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ConformalFLASH treatment delivery feasibility	Delivery of ≥ 95% of the prescribed dose to ≥ 95% of the clinical target volume (CTV) at an average dose rate of ≥ 40 GyRBE/second	Through treatment completion (within 1 month after last fraction)
Acute toxicities	Incidence of acute toxicity as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 6.0	Up to 3 months after treatment start

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ConformalFLASH treatment delivery accuracy	Dose delivered to the clinical target volume (CTV) and organs at risk (OARs) as well as the average dose rate to the CTV	Through treatment completion (within 1 month after last fraction)
Late toxicities	Incidence of late toxicity as assessed by CTCAE version 6.0	Beyond 3 months after start of treatment and up to 5 years
Local Control	Absence of tumor recurrence or progression at the primary radiated disease site following initiation of study treatment, as assessed by imaging, supplemented by clinical examination and with biopsy confirmation when indicated	3 months and 1 year
Regional control	Absence of tumor recurrence or progression in regional lymph nodes following initiation of study treatment, as assessed by imaging, supplemented by clinical examination and with biopsy confirmation when indicated	3 months and 1 year
Metastasis-free survival	Time from first treatment to the first occurrence of distant metastatic disease or death from any cause.	3 months and 1 year
Overall survival	Time from first treatment to death from any cause	3 months and 1 year
Patient-reported quality of life	Effect of the treatment on patient-reported quality of life, using the University of Washington Quality of Life Questionnaire (UW-QOL).The UW-QOL consists of domains based upon discrete ordinal responses regarding their past 7 days. Scoring is scaled so that a score of 0 represents the worst possible response, and a score of 100 represents the best possible response. The UW-QOL comprises 12 single-question domains, each between 3 and 6 response options. These options are scaled evenly from 0 (worst) to 100 (best), according to the hierarchy of response. Each domain is scored individually, and an overall composite score can be derived. In addition, patients are asked to choose up to 3 of these domains that they consider most important to them. The UW-QOL also includes 3 global questions, one about how patient feel relative to before they developed their cancer, one about their health-related QOL and one about their overall QOL.	Up to 5 years

Collaborators and Investigators

• Sponsor: IBA Proton Therapy, Inc.
• Collaborators: University of Pennsylvania
• Investigators: Principal Investigator: Alexander Lin, MD, University of Pennsylvania

Publications and helpful links

General 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.2014.11.023. Epub 2015 Jan 30.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2032

Study Registration Dates

• First Submitted: June 2, 2026
• First Submitted That Met QC Criteria: June 11, 2026
• First Posted (Actual): June 12, 2026

Study Record Updates

• Last Update Posted (Actual): June 12, 2026
• Last Update Submitted That Met QC Criteria: June 11, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Proton Therapy; Ultra-High Dose-Rate
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Head and Neck Neoplasms
• Other Study ID Numbers: IBA-04-UP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes