Carbon Ion Re-Radiotherapy in Patients With Recurrent or Progressive Locally Advanced Head-and-Neck Cancer (CARE)

Carbon Ion Re-Radiotherapy in Patients With Recurrent or Progressive Locally Advanced Head-and-Neck Cancer: A Phase-II Study to Evaluate Toxicity and Efficacy

After multimodal therapy of head-and-neck tumors, patients often develop local recurrence, locally progressive disease or second primary tumors. In this highly pre-treated patient cohort, therapeutic options are limited. Patients that are not candidates for salvage surgery may benefit from re-irradiation. Despite recent technical advances, re-irradiation is associated with severe side effects. Carbon ion Re-Radiotherapy (reCIRT) has shown encouraging results in retrospective analyses with moderate toxicity.

In the current Phase-II CARE-trial, reCIRT and conventional photon re-irradiation in patients with recurrent or progressive locally advanced head-and-neck cancer will be assessed regarding toxicity/ safety, local progression-free survival, overall survival and quality-of-life.

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced Head-and-Neck Cancer
• Intervention / Treatment: Radiation: C12 re-irradiation; Radiation: Photon re-irradiation

Detailed Description

The incidence of head-and-neck cancer worldwide amounts to around 550.000 cases per year, with male patients affected significantly more often. Common risk factors are smoking, alcohol, viral infections, immunodeficiency or genetic factors. Locally advanced head-and-neck tumors can lead to severe symptoms such as dysphagia, cachexia and tumor pain with a significant decrease of the quality-of-life. The prognosis depends on multiple factors such as TNM-staging, tumor volume, histology, general condition, age and smoking. Further risk factors are positive resection margins, extracapsular extension and perineural invasion. While metastatic spread significantly decreases overall survival, the life-limiting problem in patients with head-and-neck cancer is locally invasive and destructive tumor growth leading to a decrease of the performance status and quality of life. After multimodal therapy of locally advanced head-and-neck tumors, around 30 - 50% of patients will develop local recurrence or locally progressive disease and up to 8% of patients with HNSCC will develop a second primary tumor in the head-and-neck .

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sebastian Adeberg, PD; Phone Number: 35754 49 622156; Email: sebastian.adeberg@med.uni-heidelberg.de
• Study Contact Backup: Name: Hommertgen Adriane, PhD; Phone Number: 34091 49 622156; Email: adriane.hommertgen@med.uni-heidelberg.de

Study Locations

• Germany
  • Heidelberg, Germany, 69120
    • Recruiting
    • University Hospital of Heidelberg, Radiation Oncology
    • Contact: Jürgen Debus, Prof. Dr.; Phone Number: 8202 +49-6221-56; Email: juergen.debus@med.uni-heidelberg.de
    • Contact: Adriane Hommertgen; Phone Number: 34091 +49-6221-56; Email: adriane.hommertgen@med.uni-heidelberg.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Locally recurrent / progressive head-and-neck cancer after initial radiation therapy
• Microscopic or macroscopic tumor after salvage surgery
• Indication for re-irradiation
• Completed wound healing after surgical intervention
• Karnofsky-Performance-Score ≥ 60
• Age ≥ 18 years
• Written informed consent (must be available before enrolment in the trial)
• Ability of subject to understand character and individual consequences of the trial
• For women with childbearing potential, (and men) adequate contraception
• Submission of previous radiotherapy records

Exclusion Criteria:

• Re-irradiation of malignancy in the larynx
• Diagnosed plasmocytoma, sarcoma or chordoma
• Previous re-irradiation in-field
• Time interval < 6 months after initial radiotherapy
• Distant metastases (except pulmonary metastases)
• Patients who have not recovered from acute toxicities of prior therapies
• Refusal of the patients to take part in the study
• Pregnant or lactating women
• Known carcinoma <5 years ago (excluding Carcinoma in situ of the cervix, basal cell carcinoma, squamous cell carcinoma of the skin) requiring immediate treatment interfering with study therapy
• Participation in another clinical study or observation period of competing trials, respectively

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: C12 irradiation; Evaluation of Safety and Toxicity of C12 ion reirradiation	Radiation: C12 re-irradiation; 51 Gy(RBE) or 54 Gy
Active Comparator: Photon irradiation; Evaluation of Safety and Toxicity of photon re-irradiation	Radiation: Photon re-irradiation; 54 Gy(RBE) or 60 Gy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
safety of carbon ion re-irradiation	the rate of patients with an acute/subacute toxicity CTCAE v5.0 ≥ grade 3	6 month
toxicity of carbon ion re-irradiation	the rate of patients with an acute/subacute toxicity CTCAE v5.0 ≥ grade 3	6 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression-free survival	Local progression-free survival	12 month
Overall survival	within 12 month after re-irradiation	12 month
Score on EORTC QLQ C30 Quality of life questionaire	EORTC (European Organization for Research and. Treatment of Cancer) QLQ (quality of life questionnaire) C30, score 1-6, high score means worse outcome	within 12 month after re-irradiation
Score on EORTC QLQ H&N35 Quality of life questionaire	QLQ (quality of life questionnaire)-H&N (Head and neck) 35, score 1-6, high score means worse outcome	within 12 month after re-irradiation

Collaborators and Investigators

• Sponsor: University Hospital Heidelberg

Publications and helpful links

General Publications

• Held T, Lang K, Regnery S, Weusthof K, Hommertgen A, Jakel C, Tonndorf-Martini E, Krisam J, Plinkert P, Zaoui K, Freudlsperger C, Moratin J, Krauss J, Harrabi SB, Herfarth K, Debus J, Adeberg S. Carbon ion reirradiation compared to intensity-modulated re-radiotherapy for recurrent head and neck cancer (CARE): a randomized controlled trial. Radiat Oncol. 2020 Aug 5;15(1):190. doi: 10.1186/s13014-020-01625-0.

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2020
• Primary Completion (Estimated): November 30, 2024
• Study Completion (Estimated): November 30, 2024

Study Registration Dates

• First Submitted: November 25, 2019
• First Submitted That Met QC Criteria: December 2, 2019
• First Posted (Actual): December 4, 2019

Study Record Updates

• Last Update Posted (Actual): January 5, 2024
• Last Update Submitted That Met QC Criteria: January 4, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms
• Other Study ID Numbers: RADONK-CARE-2018

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: No