DAHANCA 37. Re-irradiation With Proton Radiotherapy

DAHANCA 37 A Phase II Study of Intensity Modulated Proton Therapy (IMPT) for Re-irradiation With Curative Intent for Recurrent or New Primary Head and Neck Cancer

Summary Design Phase II observational

Treatment

• 60 Gy/50 fx / 10W-1 at 1.2 Gy/fx

  o i.e. EQD2 tumor=56 Gy, EQD2 late=50.4 Gy at α/β= 10 and 3, respectively

• Proton radiotherapy
• Concomitant cisplatin for eligible patients*
• Nimorazole recommended for SCC* *The concurrent medical treatment (weekly cisplatin and nimorazole) are prescribed according to the national treatment guidelines, and are not part of the experimental treatment.

Endpoints

• Primary:

  o Any new late toxicity grade >=3 according to CTC AE 5.0

• Secondary

  • Side effects according to DAHANCA scoring system
  • Quality of life and PROM according to EORTC C30 and HN43
  • Loco-regional control (LRC)
  • Overall survival (OS)

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Neoplasms
• Intervention / Treatment: Radiation: Re-irradiation

Detailed Description

Summary Design Phase II observational Inclusion criteria

• Histological verified loco-regional recurrence or new primary
• Available dose plan from primary radiotherapy course
• Comparative dose plan with advantages for proton radiotherapy e.g. integral dose
• Dmax dose (0.03 cm3) on the cumulated photon dose plan≥90 Gy
• Complete Response (CR)* after initial therapy, except in the case where the recurrence is considered a geometric miss (recurrence center of mass (COM) outside the 95% of prescription dose.
• Inoperable or salvage surgery with R1/R2 resection, extranodal extension (ENE) or extensive soft tissue infiltration

• Absence of distant metastasis at both

  • clinical examination AND
  • PET-CT or CT of thorax and upper abdomen
• Life expectancy due to age and co-morbidity of >=1 year. The general condition must be sufficient to tolerate persistent significant side effects, e.g. tube or cannulae
• PS<=2 (WHO See appendix)

• The patients should be able to read Danish in order to participate with quality of life questionnaires, but can participate in the rest of the protocol without being fluent in Danish, if capable of reading the patient information.

  * Complete Response is defined as the situation when a trained clinician, ideally at a multidisciplinary team conference, defines the patient as in complete remission, based on clinical examination and available imaging. This status can of course later be considered wrong as new information becomes available (sub-centimeter nodes grow etc.) Exclusion criteria

• Radical surgery (R0) and absence of adverse prognostic pathological features
• Lymphoma or malignant melanoma
• Inability to attend full course of radiotherapy or follow-up visits in the outpatient clinic
• As of 2019, patients with tracheal cannulas are excluded due to dose uncertainties. This may change if a technical solution becomes available.

Treatment

• 60 Gy/50 fx / 10W-1 at 1.2 Gy/fx

  o i.e. EQD2 tumor=56 Gy, EQD2 late=50.4 Gy at α/β= 10 and 3, respectively

• Proton radiotherapy
• Concomitant cisplatin for eligible patients*
• Nimorazole recommended for SCC* *The concurrent medical treatment (weekly cisplatin and nimorazole) are prescribed according to the national treatment guidelines, and are not part of the experimental treatment.

Endpoints

• Primary:

  o Any new late toxicity grade >=3 according to CTC AE 5.0

• Secondary

  • Side effects according to DAHANCA scoring system
  • Quality of life and PROM according to EORTC C30 and HN43
  • Loco-regional control (LRC)
  • Overall survival (OS)

Derived projects

• Morbidity (NTCP) modeling for cumulative doses
• Metrics for uncertainties regarding cumulative doses

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kenneth Jensen, PhD; Phone Number: +45 21284108; Email: kennjens@rm.dk
• Study Contact Backup: Name: Jesper Eriksen, Professor; Email: jesper@oncology.au.dk

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Recruiting
    • Danish Center for Particle Therapy
    • Contact: Kenneth Jensen, Ph.D.; Phone Number: 45 78450000; Email: kennjens@rm.dk
    • Contact: Dorte Winther, Nurse; Phone Number: 78450000; Email: dorte.skriver.winther@auh.rm.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histological verified loco-regional recurrence or new primary
• Available dose plan from primary radiotherapy course
• Comparative dose plan with advantages for proton radiotherapy e.g. integral dose
• Dmax dose (0.03 cm3) on the cumulated photon dose plan≥90 Gy
• Complete Response (CR)* after initial therapy, except in the case where the recurrence is considered a geometric miss (recurrence center of mass (COM) outside the 95% of prescription dose.
• Inoperable or salvage surgery with R1/R2 resection, extranodal extension (ENE) or extensive soft tissue infiltration

• Absence of distant metastasis at both

  • clinical examination AND
  • PET-CT or CT of thorax and upper abdomen
• Life expectancy due to age and co-morbidity of >=1 year. The general condition must be sufficient to tolerate persistent significant side effects, e.g. tube or cannulae
• PS<=2 (WHO See appendix)

Exclusion Criteria:

• Radical surgery (R0) and absence of adverse prognostic pathological features
• Lymphoma or malignant melanoma
• Inability to attend full course of radiotherapy or follow-up visits in the outpatient clinic
• As of 2019, patients with tracheal cannulas are excluded due to dose uncertainties. This may change if a technical solution becomes available.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Re-Irradiation with protons; 60 Gy in 50 fraktions, 10 weekly with protons	Radiation: Re-irradiation; Cisplatin for all eligible patients, nimorazole for all SCC; Other Names: cisplatin; nimorazole

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Any new grade >=3 toxicity	CTC AE 5.0	3 years after radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side effects, any grade	According to CTC AE or Dahanca	5 years after radiotherapy
Quality of life and PROM	EORTC QLQ HN43 , swallowing scale. Difference (mean) between baseline and 6 months	6 months
Loco-regional control (LRC)	Abscence of locoregional failure	5 years after radiotherapy -actuarial analysis
Overall survival (OS)	Abscence of death	Median Survival up to 5 years

Collaborators and Investigators

• Sponsor: Danish Head and Neck Cancer Group
• Investigators: Principal Investigator: Kenneth Jensen, Danish Centre for Particle Therapy

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2019
• Primary Completion (ANTICIPATED): August 30, 2021
• Study Completion (ANTICIPATED): August 30, 2025

Study Registration Dates

• First Submitted: May 30, 2019
• First Submitted That Met QC Criteria: June 7, 2019
• First Posted (ACTUAL): June 10, 2019

Study Record Updates

• Last Update Posted (ACTUAL): September 25, 2020
• Last Update Submitted That Met QC Criteria: September 23, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: recurrent; reirradiation; second primary
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Anti-Infective Agents; Antineoplastic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antitrichomonal Agents; Cisplatin; Nimorazole
• Other Study ID Numbers: Dahanca 37

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