Adaptative Radiotherapy to Decrease Xerostomia in Oropharynx Carcinoma (ARTIX)

Phase III Trial Testing the Benefit of Intensity-modulated Radiotherapy With Weekly Replanifications Versus Intensity Modulated Radiotherapy With Only One Planification in Locally Advanced Oropharynx Carcinoma for Decreasing Xerostomia

The Phase III study will include 174 patients with locally advanced oropharynx carcinoma, receiving all arc-IMRT (Intensity-Modulated Radiation Therapy) (70 Gy) with concomitant systemic therapy. Two arc-IMRT treatment arms will be compared: one "standard" arm based on the use of a single pre-treatment planning and one "experimental" arm (adaptive RT) based on a weekly replanning to spare the salivary glands. The main objective is to increase by 25% the salivary flow (Parafilm) 12 months after RT thanks to adaptive RT, while not decreasing local control. The secondary objectives are to increase the salivary flow (scintigraphy), reduce xerostomia, acute and late toxicities (Eisbruch questionnaire, MDAS-HN, v.4 CTCAE), while maintaining local control (stopping rule of the trial if difference>15%). 174 patients will be included in 6 French centers for 2 years and followed for 2 years. The HPV (Human Papillomavirus) status will be identified and the tumors frozen. A central IMRT QA (Quality Assurance) will be performed.

Study Overview

• Status: Completed
• Conditions: Oropharynx Cancer
• Intervention / Treatment: Radiation: adaptative radiotherapy

• Study Type: Interventional
• Enrollment (Actual): 132
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Albi, France
    • Clinique Claude Bernard
  • Brest, France, 29200
    • Clinique Pasteur - Saint Esprit
  • Caen, France, 14076
    • CRLCC Baclesse
  • Lille, France, 59020
    • CRLCC Oscar Lambret
  • Lyon, France
    • Centre Leon Berard
  • Nice, France, 06189
    • CRLCC Antoine Lacassagne
  • Poitiers, France, 86000
    • CHU de la Milétrie
  • Rennes, France, 35042
    • Centre Eugene Marquis
  • Rouen, France
    • Crlcc Henri Becquerel
  • Strasbourg, France
    • Centre Paul Strauss
  • Tours, France, 37044
    • Chu Tours

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Locally advanced non-metastatic carcinoma of the oropharynx limited to T3 and T4 (whatever the N) and N2-N3 (whatever the T)(AJCC stage III-IV)
2. Age ≥ 18 years and ≤ 75 years
3. Performance status (WHO ≤ 2)
4. Renal, hepatic and cardiovascular functions allowing systemic treatment administration
5. Adapted stomatologic care
6. Signed informed consent form
7. Membership or beneficiary of a national insurance scheme

Exclusion Criteria:

1. Both parotids totally included in the target volume
2. Stages T1 or T2 with positive node disease N1
3. Neoadjuvant chemotherapy
4. Exereses of primitive tumor and/or nodes
5. History of other cancer within 5 years (except for basocellular epithelioma and cervical)
6. Previous neck radiotherapy
7. Platinum salts, 5FluoroUracile (5FU) agents or cetuximab chemotherapy considerations
8. Unstable diseases (cardiovascular, renal, pulmonary, systemic lupus or sclerodermia)incompatible with study participation
9. Patient participating in other therapeutic trial with experimental drug, 30 days before the inclusion.
10. Patient already recruited in another biomedical research ( non interventional study is authorized)
11. Pregnant or breast feeding patients
12. Patient deprived of liberty, under tutorship, guardianship or placed under judicial protection
13. Patient is deemed incapable of giving informed consent
14. Patients who, for family, social, geographic or psychological reasons, cannot be adequately followed up and/or are incapable of undergoing regular controls.

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
No Intervention: standard radiotherapy; single pre-treatment planning before radiotherapy
Experimental: adaptative radiotherapy; adaptive Radiotherapy based on a weekly replanning	Radiation: adaptative radiotherapy; weekly replanning

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Salivary flow measure	The salivary flow is measured after stimulation with Parafilm at the time of inclusion and then 12 months after the end of radiotherapy.	12 months after the end of radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Xerostomia	salivary flow measured after stimulation before treatment, 6months, 18 months and 24 months after the end of radiotherapy Eisbruch's questionnaire before treatment, at 3, 6, 12, 18 and 24 months after the end of radiotherapy	From before treatment to 24 months after the end of radiotherapy
Salivary flow	measured by scintigraphy	Before treatment and 12 months after the end of radiotherapy
Local control	analysed according stages T and N, HPV status	2 years
Early and late toxicities	early toxicity : weekly assessment during radiotherapy until 3 months after the end late toxicity : 6, 12, 18 and 24 months after the end of radiotherapy	From beginning of the radiotherapy up to 2 years after the end of radiotherapy
Survival	overall and disease free survival	2 years
Head and Neck functionality	MDASI-HN questionnaire before treatment, 3, 6, 12, 18 and 24 months after the end of radiotherapy	Before treatment to 24 months after the end of radiotherapy

Collaborators and Investigators

• Sponsor: Center Eugene Marquis
• Investigators: Principal Investigator: Renaud De Crevoisier, MD, Centre Eugène Marquis - Rennes - France

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2013
• Primary Completion (Actual): December 10, 2019
• Study Completion (Actual): December 8, 2020

Study Registration Dates

• First Submitted: April 25, 2013
• First Submitted That Met QC Criteria: June 7, 2013
• First Posted (Estimate): June 11, 2013

Study Record Updates

• Last Update Posted (Actual): July 27, 2021
• Last Update Submitted That Met QC Criteria: July 26, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: xerostomia; Adaptative radiotherapy; oropharynx carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Mouth Diseases; Salivary Gland Diseases; Carcinoma; Oropharyngeal Neoplasms; Xerostomia
• Other Study ID Numbers: 2012-RdC-ORL-Th; 2012-A00426-37 (Registry Identifier: ANSM)