HAI-5-III: Outcome of 15 Versus 5 Fractions in Adjuvant Breast Radiotherapy in Women Over 65 Years

Sponsor

University Hospital, Ghent (Other)

Overall Status

Recruiting

CT.gov ID

NCT03121248

Collaborator

(none)

798

Enrollment

Location

Arms

119.5

Anticipated Duration (Months)

6.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will evaluate the effect of highly accelerated external beam radiotherapy (EBRT) in 5 fractions over 10 days compared to 15 fractions over 3 weeks for early as well as locally-advanced stage breast cancer.

Primary endpoint will be chronic toxicity (breast deformation and retraction). Secondary endpoints are acute toxicity, loco-regional and distant tumor control, patient reported QoL and cosmetic satisfaction. Patients with lymph node irradiation will be closely monitored for radiation induced plexopathy.

Condition or Disease	Intervention/Treatment	Phase
Breastcancer	Radiation: WBI 5 fractions Radiation: WBI 15 fractions Radiation: LNI 5 fractions Radiation: LNI 15 fractions Radiation: SIB 5 fractions if needed Radiation: SIB 15 fractions if needed Radiation: TWI 5 fractions Radiation: TWI 15 fractions	N/A

Detailed Description

Over the age of 65, uptake of adjuvant radiotherapy after surgery for breast cancer declines, even in women with poor prognostic stage or adverse tumor characteristics.

Lowering the number of fractions may reduce reluctancy for radiotherapy in this age group.

In a preceding prospective phase I-II trial, evaluating EBRT over 10 days, results on technical feasibility and acute toxicity were positively evaluated.

However, data on the chronic effects of breast irradiation using high doses per fraction are still sparse.

This trial is developed to compare standard hypo-fractionation in 15 fractions (if needed with simultaneously integrated boost - SIB) with highly accelerated radiotherapy in 5 fractions.

Patients referred for adjuvant radiotherapy after breast conserving surgery will preferably be randomized, depending on the indication, to a study-arm with whole breast irradiation (WBI) +/- SIB or to a study-arm with WBI+/- SIB and lymph node irradiation (LNI).

If patients after breast conserving surgery (BCS) have a strong preference for 5 or 15 fractions, they will be invited to enter the parallel observational arm (patient preference).

Patients referred for adjuvant radiotherapy after mastectomy +/- LNI accepting to participate, can choose a 5 or 15-fraction schedule. No randomization is foreseen in this last observational group.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

798 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Partially Randomized Patient Preference Trial, Comparing Adjuvant Hypofractionated Radiotherapy in 15 Versus 5 Fractions After Breast Conserving Surgery or Mastectomy for Early or Locally Advanced Breast Cancer in Women Above 65 Years

Actual Study Start Date :

Feb 15, 2017

Anticipated Primary Completion Date :

Jan 31, 2022

Anticipated Study Completion Date :

Jan 31, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: WBI - randomized - 5 WBI 5 fractions SIB 5 fractions if needed	Radiation: WBI 5 fractions External beam radiotherapy in 5 fractions of 5,7Gy Radiation: SIB 5 fractions if needed Simultaneous boost of 5 x 6,2Gy (6,5Gy in case of involved resection margins) if needed
Active Comparator: WBI - randomized - 15 WBI 15 fractions SIB 15 fractions if needed	Radiation: WBI 15 fractions External beam radiotherapy in 15 fractions of 2,67Gy Radiation: SIB 15 fractions if needed Simultaneous boost of 15x3,12Gy (3,33Gy in case of involved resection margins) if needed
Experimental: WBI - observational - 5 WBI 5 fractions SIB 5 fractions if needed	Radiation: WBI 5 fractions External beam radiotherapy in 5 fractions of 5,7Gy Radiation: SIB 5 fractions if needed Simultaneous boost of 5 x 6,2Gy (6,5Gy in case of involved resection margins) if needed
Active Comparator: WBI - observational - 15 WBI 15 fractions SIB 15 fractions if needed	Radiation: WBI 15 fractions External beam radiotherapy in 15 fractions of 2,67Gy Radiation: SIB 15 fractions if needed Simultaneous boost of 15x3,12Gy (3,33Gy in case of involved resection margins) if needed
Experimental: WBI + LNI - randomized - 5 WBI 5 fractions SIB 5 fractions if needed LNI 5 fractions	Radiation: WBI 5 fractions External beam radiotherapy in 5 fractions of 5,7Gy Radiation: LNI 5 fractions External beam radiotherapy in 5 fractions of 5,4Gy Radiation: SIB 5 fractions if needed Simultaneous boost of 5 x 6,2Gy (6,5Gy in case of involved resection margins) if needed
Active Comparator: WBI + LNI - randomized - 15 WBI 15 fractions SIB 15 fractions if needed LNI 15 fractions	Radiation: WBI 15 fractions External beam radiotherapy in 15 fractions of 2,67Gy Radiation: LNI 15 fractions External beam radiotherapy in 15 fractions of 2,67Gy Radiation: SIB 15 fractions if needed Simultaneous boost of 15x3,12Gy (3,33Gy in case of involved resection margins) if needed
Experimental: WBI with LNI - observational - 5 WBI 5 fractions SIB 5 fractions if needed LNI 5 fractions	Radiation: WBI 5 fractions External beam radiotherapy in 5 fractions of 5,7Gy Radiation: LNI 5 fractions External beam radiotherapy in 5 fractions of 5,4Gy Radiation: SIB 5 fractions if needed Simultaneous boost of 5 x 6,2Gy (6,5Gy in case of involved resection margins) if needed
Active Comparator: WBI with LNI - observational - 15 WBI 15 fractions SIB 15 fractions if needed LNI 15 fractions	Radiation: WBI 15 fractions External beam radiotherapy in 15 fractions of 2,67Gy Radiation: LNI 15 fractions External beam radiotherapy in 15 fractions of 2,67Gy Radiation: SIB 15 fractions if needed Simultaneous boost of 15x3,12Gy (3,33Gy in case of involved resection margins) if needed
Experimental: thoracic wall irradiation (TWI) +/- LNI - observational - 5 TWI 5 fractions SIB 5 fractions if needed LNI 5 fractions	Radiation: LNI 5 fractions External beam radiotherapy in 5 fractions of 5,4Gy Radiation: TWI 5 fractions External beam radiotherapy in 5 fractions of 5,7Gy
Active Comparator: TWI +/- LNI - observational - 15 TWI 15 fractions SIB 15 fractions if needed LNI 15 fractions	Radiation: LNI 15 fractions External beam radiotherapy in 15 fractions of 2,67Gy Radiation: TWI 15 fractions External beam radiotherapy in 15 fractions of 2,67Gy

Outcome Measures

Primary Outcome Measures

Breast retraction (LENTSOMA) [2-5 years]
Breast Cancer Conservative treatment.core (BCCT.core) objective measurement

Secondary Outcome Measures

Acute toxicity: number of patients with clinical relevant dermatitis (CTCAE v. 4.0) [1-8 weeks]
Assessment of grade of dermatitis
Acute toxicity: number of patients with moist desquamation [1-8 weeks]
CTCAE v. 4.0 (grade 3)
Acute toxicity: number of patients with pain (CTCAE v. 4.0) [1-8 weeks]
Grade 1: mild; Grade 2: moderate, limiting activity of daily living (ADL); grade 3: severe, limiting ADL
Acute toxicity: number of patients with pruritus (CTCAE v. 4.0) [1-8 weeks]
Grade 1: mild, localized topical intervention; Grade 2: intense, oral intervention, skin changes
Acute toxicity: number of patients with fatigue (MFI-20) [1-8 weeks]
Questionnaire (20 questions)
Chronic toxicity: measurement of patient satisfaction with breast esthetic outcome [Before radiotherapy and after 2 and 5 years]
BREAST-Q questionnaire: Patient reported outcome, evaluating satisfaction with esthetic outcome.
Chronic toxicity: prevalence of fibrosis [2 and 5 years]
LENT Soma: fibrosis (score 0-3)
Chronic toxicity: prevalence of pain [2 and 5 years]
LENT Soma: score 0-4
Chronic toxicity: prevalence of telangiectasia [2 and 5 years]
LENT Soma: Score 0-3
Chronic toxicity: prevalence of lymphedema [2 and 5 years]
LENT Soma: score 0-4
Chronic toxicity: prevalence of fatigue (MFI-20) [2 and 5 years]
Questionnaire (20 questions)
Chronic toxicity - prevalence of radiation induced brachial plexopathy (RIBP) (standardized screening questionnaire), confirmed by electromyogram (EMG) [2 and 5 years]
If a screening reveals unilateral pain, loss of function or muscular atrophy in the ipsilateral arm, an EMG will be performed to confirm/exclude RIBP
Loco-regional tumor control [2 and 5 years]
Ipsilateral or regional breast recurrence
Distant tumor control [2 and 5 years]
Distant metastases free survival
Breast cancer specific survival [2 and 5 years]
Number of patients alive and without breast cancer recurrence at 2 and 5 years after adjuvant radiotherapy
Overall survival [2 and 5 years]
Number of patients alive, 2 and 5 years after adjuvant radiotherapy

Other Outcome Measures

Patient preference [Moment of intake, before allocation to study arm.]
Patients can accept clinical trial but refuse randomization. In this case they will be allocated to a patient preference study arm, existing also of a 5 or 15 fraction-schedule. The choice of the patient: acceptance or non-acceptance of study, acceptance or non-acceptance of randomization, in case of patient preference arm: acceptance or 5 or 15 fractions.
QoL within perspective of cancer patients [4 weeks, 1, 2 and 5 years]
QLQ C30 - standardised questionnaire
QoL within perspective of breast cancer patients [4 weeks, 1, 2 and 5 years]
QLQ BR23 - standardised questionnaire
QoL within perspective of healthy patients [4 weeks, 1, 2 and 5 years]
EQ-D5: standardised questionnaire
Number of patients evolving to higher frailty score after radiotherapy [4 weeks, 1, 2 and 5 years]
Measurement of frailty using G8 geriatric screening tool
Cost Effectiveness Analysis [5 years]
Cost effectiveness analysis comparing 5 with 15 fractions
Technical feasibility of prone positioning [At the moment of simulation]
Percentage of patients able to perform prone positioning on new breast board: yes or no.
Technical feasibility of deep inspirational breath-hold in prone position [At the moment of simulation]
Percentage of patients able to perform breath-hold procedure in prone position: yes or no.

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

breast conserving surgery or mastectomy for breast carcinoma
multidisciplinary decision of adjuvant irradiation
absence of distant metastases
informed consent obtained, signed and dated before specific protocol procedures

Exclusion Criteria:

History of previous radiation treatment to the same region
Bilateral breast irradiation
Life expectancy of less than 2 years
Planned reconstructive breast surgery
Condition making toxicity evaluation difficult, e.g. skin disorders, pre-existing brachial plexus injury, …
Inability to respect constraints on skin, heart, lungs, esophagus, ribs, brachial plexus or any other organ at risk
Mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study
Patient unlikely to comply with the protocol; i.e. uncooperative attitude, inability to return for follow-up visits or unlikely to complete the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ghent University Hospital, Dept. Radiotherapy-Oncology	Ghent		Belgium	9000

Sponsors and Collaborators

University Hospital, Ghent

Investigators

Principal Investigator: Liv Veldeman, M.D., PhD, Ghent University Hospital, Dept. Radiotherapy-Oncology

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

HAI-5 feasilibility trial: results acute toxicity

Publications

None provided.

Responsible Party:

University Hospital, Ghent

ClinicalTrials.gov Identifier:

NCT03121248

Other Study ID Numbers:

EC/2016/1386

First Posted:

Apr 20, 2017

Last Update Posted:

Oct 25, 2019

Last Verified:

Mar 1, 2019

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by University Hospital, Ghent

Accelerated radiotherapy

Older women

Hypo-fractonation

Additional relevant MeSH terms:

Breast Neoplasms

Study Results

No Results Posted as of Oct 25, 2019