Comparing Two Palliative Schemes of Radiotherapy for Head and Neck Cancer (COOPERATION)

Dutch Randomized Multicenter Trial COmparing twO PalliativE RAdiaTION Schemes for Incurable Head and Neck Cancer (COOPERATION)

RCT to compare two radiation schemes for palliative HeadNeck cancer

Study Overview

• Status: Terminated
• Conditions: Head and Neck Neoplasms
• Intervention / Treatment: Radiation: 6 x 6 Gy; Radiation: 16 x 3.125 Gy

Detailed Description

A substantial proportion of patients with head and neck (HNC) are not suitable for curative treatment with surgery and/or (chemo)radiotherapy (CRT) because of very advanced stage, significant comorbidities, bad general condition, distant metastasis, or a combination of these factors. Although radiotherapy (RT) is a commonly used option to achieve durable disease control and to alleviate troublesome symptoms, the data about the optimal radiation scheme and the impact of these schedules on quality of life (QoL) of these vulnerable patients is extremely scarce.

Although different radiation schemes are used worldwide (in the Netherlands, at least 15 different radiation schedules are used), it is currently not possible to identify the best RT scheme, based only on retrospective studies because of the major differences between these studies with regard to patient's demographics, radiation schedules given, the radiation technique used etc. Furthermore, no any information is available on the impact of these schemes on treatment-related toxicity and QoL.

This illustrates the urgent need for a multicenter randomized controlled trial (RCT) to identify the most optimal schemes of RT for this group of patients. Therefore, the investigators intend to initiate a prospective RCT comparing the survival, loco-regional control, toxicity, and QoL of two commonly used schemes. This study will be the first of his kind for palliative patients with HNC and will compare a short-course (6 fractions) with a long-course of radiotherapy (16 fractions). Because most of patients with incurable HNC have a poor performance status and major comorbidity and prefer limited number of visits to the hospital, it is quite reasonable to investigate whether a short scheme of radiotherapy with limited number of visits to the clinic as good as a relatively long-course of radiotherapy in terms of outcome, toxicity and QoL. This delicate balance between outcomes, possible toxicity and patient's comfort would justify the initiation of such randomized trial. The results of this study will in the nearby future enable us to indicate the radiation scheme best suits which patient category

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1081 HZ
    • Vrije Universiteit Medisch Centrum
  • Amsterdam, Netherlands, 19066CX
    • Antoni van Leeuwenhoek
  • Arnhem, Netherlands, 6815AD
    • Radiotherapiegroep, lokatie Arnhem
  • Den Haag, Netherlands, 2260 AK
    • Haaglanden Medisch Centrum
  • Groningen, Netherlands, 9700 RB
    • University Medical Center Groningen
  • Maastricht, Netherlands, NL-6229 ET
    • Maastro clinic
  • NIjmegen, Netherlands, 6225GA
    • Radboud UMC
  • Rotterdam, Netherlands, 3008EA
    • Erasmus Medisch Centrum
  • Tilburg, Netherlands, 5042 SB
    • Instituut Verbeeten
  • Overijssel
    • Enschede, Overijssel, Netherlands, 7513 ER
      • Medisch Spectrum Twente
  • Zuid Holland
    • Leiden, Zuid Holland, Netherlands, 2333 ZA
      • Leids Universitair Medisch Centrum

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:

• Newly diagnosed patients with primary non-metastatic carcinoma located in the oral cavity, oropharynx, larynx (except T1 glottic), hypopharynx, nasopharynx, paranasal sinuses and salivary gland and carcinoma of unknown primary in the head and neck region who are not suitable for radical treatment with surgery or (chemo) and, therefore, planned for treatment with radiotherapy in palliative setting.

OR

• Newly diagnosed patients with primary head and neck carcinoma with limited metastatic disease in a good general condition and few comorbidities (ACE-25 <3) with life expectancy of at least 6 months are also eligible.
• No chemotherapy or surgery is allowed before inclusion.
• Age ≥ 18 years
• WHO performance status 0-2
• Signed written informed consent

Exclusion Criteria:

• Patients with previously radiation treatment in the head and neck region, for any reason.

  * Chemotherapy or surgery for head and neck tumor before inclusion and no other concomitant anti-cancer therapy is allowed during study treatment.

• Patients with head and neck malignancies arising from skin, nose, thyroid gland or esophagus.
• Patients with advanced stage sarcoma or lymphoma of the head and neck region.
• Expected life expectancy of less than 3 months

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
Active Comparator: arm 1: 6 fractions of radiation; radiation in a 6 fractions scheme and a daily dose of 6 Gy	Radiation: 6 x 6 Gy; radiation in 6 fraction of 6 Gy, twice a week during 3 weeks
Active Comparator: arm 2: 16 fractrions of radiation; radiation in a 16 fractions scheme and a daily dose of 3.125 Gy	Radiation: 16 x 3.125 Gy; radiation in 16 fraction of 3.125 Gy, 4 times a week during 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
time to loco-regional progression	caculated from date of response until the date of clinical deteriotion; accoriding to RECIST	4 months
impact of both radiation schemes on QoL	this will be measured by the EORTC questionnaires C30 and HN35; analysis will be performed by a random effects regression model	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival rates	RECIST	4 months
loco-regional control rates	caculated from date of response until the date of clinical deteriotion; according to RECIST	3 months
overall response rates	caculated from date of response until the date of clinical deteriotion; accoriding to RECIST	2 year
compliance to the study treatments as assessed by completed treatment and follow-up visits	number of treatment fractions and follow-up visits	4 months
the incidence of grade ≥ 2 acute and late toxicity	scoring of AE according tot CTC 4.0	2 years

Collaborators and Investigators

• Sponsor: The Netherlands Cancer Institute
• Investigators: Principal Investigator: Abrahim Al-Mamgani, MD, PhD, The Netherlands Cancer Institute

Publications and helpful links

General Publications

• Al-Mamgani A, Kessels R, Verhoef CG, Navran A, Hamming-Vrieze O, Kaanders JHAM, Steenbakkers RJHM, Tans L, Hoebers F, Ong F, van Werkhoven E, Langendijk JA. Randomized controlled trial to identify the optimal radiotherapy scheme for palliative treatment of incurable head and neck squamous cell carcinoma. Radiother Oncol. 2020 Aug;149:181-188. doi: 10.1016/j.radonc.2020.05.020. Epub 2020 May 14.

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Actual): November 1, 2018
• Study Completion (Actual): November 1, 2018

Study Registration Dates

• First Submitted: February 12, 2015
• First Submitted That Met QC Criteria: April 15, 2015
• First Posted (Estimate): April 20, 2015

Study Record Updates

• Last Update Posted (Actual): June 28, 2019
• Last Update Submitted That Met QC Criteria: June 26, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms
• Other Study ID Numbers: M15CRH

Drug and device information, study documents

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