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

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ClinicalTrials.gov Identifier: NCT03121248
Recruitment Status : Recruiting
First Posted : April 20, 2017
Last Update Posted : April 20, 2017
Sponsor:
Information provided by (Responsible Party):
University Hospital, Ghent

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 Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Estimated 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 : February 15, 2017
Estimated Primary Completion Date : January 31, 2022
Estimated Study Completion Date : January 31, 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

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




Primary Outcome Measures :
  1. Breast retraction (LENTSOMA) [ Time Frame: 2-5 years ]
    Breast Cancer Conservative treatment.core (BCCT.core) objective measurement


Secondary Outcome Measures :
  1. Acute toxicity: number of patients with clinical relevant dermatitis (CTCAE v. 4.0) [ Time Frame: 1-8 weeks ]
    Assessment of grade of dermatitis

  2. Acute toxicity: number of patients with moist desquamation [ Time Frame: 1-8 weeks ]
    CTCAE v. 4.0 (grade 3)

  3. Acute toxicity: number of patients with pain (CTCAE v. 4.0) [ Time Frame: 1-8 weeks ]
    Grade 1: mild; Grade 2: moderate, limiting activity of daily living (ADL); grade 3: severe, limiting ADL

  4. Acute toxicity: number of patients with pruritus (CTCAE v. 4.0) [ Time Frame: 1-8 weeks ]
    Grade 1: mild, localized topical intervention; Grade 2: intense, oral intervention, skin changes

  5. Acute toxicity: number of patients with fatigue (MFI-20) [ Time Frame: 1-8 weeks ]
    Questionnaire (20 questions)

  6. Chronic toxicity: measurement of patient satisfaction with breast esthetic outcome [ Time Frame: Before radiotherapy and after 2 and 5 years ]
    BREAST-Q questionnaire: Patient reported outcome, evaluating satisfaction with esthetic outcome.

  7. Chronic toxicity: prevalence of fibrosis [ Time Frame: 2 and 5 years ]
    LENT Soma: fibrosis (score 0-3)

  8. Chronic toxicity: prevalence of pain [ Time Frame: 2 and 5 years ]
    LENT Soma: score 0-4

  9. Chronic toxicity: prevalence of telangiectasia [ Time Frame: 2 and 5 years ]
    LENT Soma: Score 0-3

  10. Chronic toxicity: prevalence of lymphedema [ Time Frame: 2 and 5 years ]
    LENT Soma: score 0-4

  11. Chronic toxicity: prevalence of fatigue (MFI-20) [ Time Frame: 2 and 5 years ]
    Questionnaire (20 questions)

  12. Chronic toxicity - prevalence of radiation induced brachial plexopathy (RIBP) (standardized screening questionnaire), confirmed by electromyogram (EMG) [ Time Frame: 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

  13. Loco-regional tumor control [ Time Frame: 2 and 5 years ]
    Ipsilateral or regional breast recurrence

  14. Distant tumor control [ Time Frame: 2 and 5 years ]
    Distant metastases free survival

  15. Breast cancer specific survival [ Time Frame: 2 and 5 years ]
    Number of patients alive and without breast cancer recurrence at 2 and 5 years after adjuvant radiotherapy

  16. Overall survival [ Time Frame: 2 and 5 years ]
    Number of patients alive, 2 and 5 years after adjuvant radiotherapy


Other Outcome Measures:
  1. Patient preference [ Time Frame: 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.

  2. QoL within perspective of cancer patients [ Time Frame: 4 weeks, 1, 2 and 5 years ]
    QLQ C30 - standardised questionnaire

  3. QoL within perspective of breast cancer patients [ Time Frame: 4 weeks, 1, 2 and 5 years ]
    QLQ BR23 - standardised questionnaire

  4. QoL within perspective of healthy patients [ Time Frame: 4 weeks, 1, 2 and 5 years ]
    EQ-D5: standardised questionnaire

  5. Number of patients evolving to higher frailty score after radiotherapy [ Time Frame: 4 weeks, 1, 2 and 5 years ]
    Measurement of frailty using G8 geriatric screening tool

  6. Cost Effectiveness Analysis [ Time Frame: 5 years ]
    Cost effectiveness analysis comparing 5 with 15 fractions

  7. Technical feasibility of prone positioning [ Time Frame: At the moment of simulation ]
    Percentage of patients able to perform prone positioning on new breast board: yes or no.

  8. Technical feasibility of deep inspirational breath-hold in prone position [ Time Frame: At the moment of simulation ]
    Percentage of patients able to perform breath-hold procedure in prone position: yes or no.



Information from the National Library of Medicine

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Ages Eligible for Study:   65 Years and older   (Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03121248


Contacts
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Contact: Chris Monten, M.D. +32 9 332 3015 chris.monten@uzgent.be
Contact: Annick Van Greveling +32 9 332 3015 annick.vangreveling@uzgent.be

Locations
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Belgium
Ghent University Hospital, Dept. Radiotherapy-Oncology Recruiting
Ghent, Belgium, 9000
Contact: Chris Monten, M.D.    +32 9 332 3015    chris.monten@uzgent.be   
Contact: Liv Veldeman, M.D., PhD    +32 9 332 3015    Liv.veldeman@uzgent.be   
Sponsors and Collaborators
University Hospital, Ghent
Investigators
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Principal Investigator: Liv Veldeman, M.D., PhD Ghent University Hospital, Dept. Radiotherapy-Oncology

Additional Information:
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Responsible Party: University Hospital, Ghent
ClinicalTrials.gov Identifier: NCT03121248     History of Changes
Other Study ID Numbers: EC/2016/1386
First Posted: April 20, 2017    Key Record Dates
Last Update Posted: April 20, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Ghent:
Accelerated radiotherapy
Older women
Hypo-fractonation

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases