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MRI-guided Single Dose Preoperative Radiotherapy in Low-risk Breast Cancer (ABLATIVE-2)

Primary Purpose

Breast Cancer

Status
Withdrawn
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
MR-guided single dose preoperative PBI
Sponsored by
UMC Utrecht
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring Radiotherapy

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • WHO performance scale ≤2.

  • Females at least 50 years of age with unifocal cT1N0 breast cancer or females at least 70 years of age with unifocal cT1-2(maximum 3 cm)N0 breast cancer on mammography, ultrasound and MRI.

    • Patients with an indication for chemotherapy or immunotherapy according to Dutch National Oncoline Guidelines or own hospital protocols are not eligible. Patients with an indication for endocrine therapy are eligible.
    • Tumor size as assessed on MRI.

  • On tumor biopsy:

    • Bloom-Richardson grade 1 or 2.
    • Non-lobular invasive histological type carcinoma.
    • LCIS or (non-extensive) DCIS is accepted.
    • ER positive tumor receptor.
    • HER2 negative tumor.
  • Tumor-negative sentinel node.
  • Adequate communication and understanding skills of the Dutch language.

Exclusion Criteria:

  • Legal incapacity.
  • BRCA1, BRCA2 or CHEK2 gene mutation.
  • Previous history of breast cancer or DCIS.
  • Other type of malignancy within 5 years before breast cancer diagnosis. Patients with adequately treated malignancy longer than 5 years before breast cancer diagnosis are eligible for inclusion. For adequately treated carcinoma in situ of the cervix or basal cell carcinoma of the skin no specific time span to breast cancer diagnosis is required for inclusion.
  • Collagen synthesis disease.
  • Signs of extensive DCIS component on histological biopsy or imaging.
  • Invasive lobular carcinoma.
  • MRI absolute contraindications as defined by the Department of Radiology.
  • Nodal involvement with cytological or histological confirmation.
  • Indication for treatment with (neo-)adjuvant chemotherapy.
  • Non-feasible dosimetric RT plan.

Sites / Locations

  • UMC Utrecht

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

MR-guided single dose preoperative PBI

Arm Description

Outcomes

Primary Outcome Measures

Pathologic complete response (pCR)
pCR is assessed 6 or 12 months following single dose radiotherapy. Patients will undergo breast-conserving surgery.

Secondary Outcome Measures

Radiologic response on MRI
A 3T MRI will be made 1 week, 3 months, 6 months, 9 months and 12 months following radiotherapy. This will be correlated to the pathologic response.
Biopsy of irradiated tumor
A biopsy of the irradiated tumor will be taken before surgery, this will be evaluated for presence of tumor cells. This will be correlated to the pathologic response.
Treatment-induced toxicity
Radiotherapy- and surgery-induced toxicity will be assessed up to 10 years following radiotherapy according to Common Terminology Criteria for Adverse Events (CTCAE) v4.03.
Patient reported outcomes - quality of life
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Cancer-30 (C30), a cancer specific questionnaire on quality of life. The C30 consists of the global quality of life (scale 0-100, higher scores indicate higher quality of life), 5 functional domains (physical, role, emotional, cognitive and social functioning, scale 0-100, higher scores indicate better functioning) and 9 symptom domains (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties, scale 0-100, higher scores indicate more symptoms). No total score is calculated.
Patient reported outcomes - quality of life
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Breast-23 (BR23), a breast cancer specific questionnaire on quality of life. The BR23 consists of 4 functional domains (body image, sexual functioning, sexual enjoyment and future perspectives, scale 0-100, higher scores indicate better functioning) and 4 symptom domains (systemic therapy side effects, breast symptoms, arm symptoms and upset by hair loss, scale 0-100, higher scores indicate more symptoms) . No total score is calculated.
Patient reported outcomes - anxiety and depression
Anxiety and depression (Hospital Anxiety and Depression Scale): The scales ranges from 0 to 21 for both domains anxiety and depression separately. Higher scores indicate more complaints of anxiety or depression. No total score is calculated.
Patient reported outcomes - fatigue
Fatigue (Multidimensional Fatigue Index). Five dimensions are present: General fatigue, physical fatigue, reduced activity, reduced motivation and mental fatigue. All dimensions range from 4-20, higher scores indicate more symptoms of fatigue on the specific dimension. No total score is calculated.
Patient reported outcomes - work ability
Work ability (Work Ability Index). Seven dimensions are present: current work ability compared to best work ability (scale 0-10), work ability compared to demands of work (scale 2-10), current number of disease (scale 1-7),loss of work ability due to disease (scale 1-6), absenteeism past 12 months (scale 1-5), prognosis work ability in 2 years (scale 1-7), vitality (scale 1-4). A total score of work ability is calculated as the sum of all dimension (scale 7-49). In all dimension higher scores indicate better work ability.
Patient reported outcomes - frailty
Frailty (Groningen Frailty Indicator), one dimension (scale 0-15), higher scores indicate higher level of frailty.
Patient reported outcomes - satisfaction with cosmesis
Satisfaction with cosmesis (questionnaire by Sneeuw et al. and BREAST-Q)). The questionnaire by Sneeuw et al. consists of seven questions, no total score is calculated. These questions are about difference between the treated and untreated breast in terms of size, shape, skin color, firmness and overall cosmesis (scale: no difference, small difference, moderate difference, large difference), visibility of the surgical scar (scale: not distracting, little distracting, quite distracting, very distracting) and satisfaction with the appearance of the treated breast (scale: very satisfied, satisfied, not unsatisfied, unsatisfied, very unsatisfied). No total score is calculated. From the BREAST-Q questionnaire only the postoperative domain of satisfaction with the breasts is used (scale 0-100), higher scores indicate more satisfaction.
Local, regional and distant relapse rate
Recurrences up to 10 years following radiotherapy will be evaluated.
Disease free survival
Disease free survival will be evaluated as the interval between treatment and first date of recurrence of disease.
Overall survival
Overall survival will be evaluated as interval between treatment and death.
Tumor infiltrating lymphocytes
The presence of tumor infiltrating lymphocytes in the tumor will be assessed at baseline (using the diagnostic biopsy) and following treatment (using the surgical resection). This will be correlated to the pathologic response.
Circulating tumor DNA
Patients will be evaluated for the presence of circulating tumor DNA at baseline and following radiotherapy. This will be correlated to the pathologic response.

Full Information

First Posted
January 15, 2019
Last Updated
February 23, 2021
Sponsor
UMC Utrecht
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1. Study Identification

Unique Protocol Identification Number
NCT03863301
Brief Title
MRI-guided Single Dose Preoperative Radiotherapy in Low-risk Breast Cancer
Acronym
ABLATIVE-2
Official Title
MRI-guided Single Dose Preoperative Radiotherapy in Low-risk Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Withdrawn
Why Stopped
no participants enrolled
Study Start Date
March 4, 2019 (Anticipated)
Primary Completion Date
November 2022 (Anticipated)
Study Completion Date
November 2031 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
UMC Utrecht

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This study aims to evaluate the pathologic response at 12 months after single dose preoperative partial breast irradiation in early stage breast cancer patients. Furthermore, the aim is to collect data on response monitoring. Patient-reported outcome measures and treatment-induced toxicity will be evaluated.
Detailed Description
In this multi-center single arm interventional cohort study 70 patients will be treated with single dose preoperative partial breast irradiation (PBI). Breast conserving surgery will be performed 12 months following PBI to assess pathologic response. Response monitoring following PBI includes MRI (3T and 7T), liquid biopsies and biopsy of the irradiated tumor. Results from this trial can change the current treatment of patients with early stage breast cancer. The single dose PBI can be of benefit for all patients who are suitable for postoperative PBI according to current guidelines. If pathologic complete response can be accurately predicted by (one of) the abovementioned response monitoring modalities, the need for surgery will become disputable. Moreover, in patients without expected pathologic complete response, the burden of radiotherapy can be minimized from 3-4.5 weeks of radiotherapy to a single dose of radiotherapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
Radiotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Single arm interventional cohort study
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
MR-guided single dose preoperative PBI
Arm Type
Experimental
Intervention Type
Radiation
Intervention Name(s)
MR-guided single dose preoperative PBI
Intervention Description
A single dose of 20Gy to the gross tumor volume (GTV) is prescribed, to the clinical target volume (GTV + 20mm margin) 15Gy is prescribed.
Primary Outcome Measure Information:
Title
Pathologic complete response (pCR)
Description
pCR is assessed 6 or 12 months following single dose radiotherapy. Patients will undergo breast-conserving surgery.
Time Frame
up to 12 months
Secondary Outcome Measure Information:
Title
Radiologic response on MRI
Description
A 3T MRI will be made 1 week, 3 months, 6 months, 9 months and 12 months following radiotherapy. This will be correlated to the pathologic response.
Time Frame
up to 12 months
Title
Biopsy of irradiated tumor
Description
A biopsy of the irradiated tumor will be taken before surgery, this will be evaluated for presence of tumor cells. This will be correlated to the pathologic response.
Time Frame
up to 12 months
Title
Treatment-induced toxicity
Description
Radiotherapy- and surgery-induced toxicity will be assessed up to 10 years following radiotherapy according to Common Terminology Criteria for Adverse Events (CTCAE) v4.03.
Time Frame
10 years
Title
Patient reported outcomes - quality of life
Description
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Cancer-30 (C30), a cancer specific questionnaire on quality of life. The C30 consists of the global quality of life (scale 0-100, higher scores indicate higher quality of life), 5 functional domains (physical, role, emotional, cognitive and social functioning, scale 0-100, higher scores indicate better functioning) and 9 symptom domains (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties, scale 0-100, higher scores indicate more symptoms). No total score is calculated.
Time Frame
10 years
Title
Patient reported outcomes - quality of life
Description
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Breast-23 (BR23), a breast cancer specific questionnaire on quality of life. The BR23 consists of 4 functional domains (body image, sexual functioning, sexual enjoyment and future perspectives, scale 0-100, higher scores indicate better functioning) and 4 symptom domains (systemic therapy side effects, breast symptoms, arm symptoms and upset by hair loss, scale 0-100, higher scores indicate more symptoms) . No total score is calculated.
Time Frame
10 years
Title
Patient reported outcomes - anxiety and depression
Description
Anxiety and depression (Hospital Anxiety and Depression Scale): The scales ranges from 0 to 21 for both domains anxiety and depression separately. Higher scores indicate more complaints of anxiety or depression. No total score is calculated.
Time Frame
10 years
Title
Patient reported outcomes - fatigue
Description
Fatigue (Multidimensional Fatigue Index). Five dimensions are present: General fatigue, physical fatigue, reduced activity, reduced motivation and mental fatigue. All dimensions range from 4-20, higher scores indicate more symptoms of fatigue on the specific dimension. No total score is calculated.
Time Frame
10 years
Title
Patient reported outcomes - work ability
Description
Work ability (Work Ability Index). Seven dimensions are present: current work ability compared to best work ability (scale 0-10), work ability compared to demands of work (scale 2-10), current number of disease (scale 1-7),loss of work ability due to disease (scale 1-6), absenteeism past 12 months (scale 1-5), prognosis work ability in 2 years (scale 1-7), vitality (scale 1-4). A total score of work ability is calculated as the sum of all dimension (scale 7-49). In all dimension higher scores indicate better work ability.
Time Frame
10 years
Title
Patient reported outcomes - frailty
Description
Frailty (Groningen Frailty Indicator), one dimension (scale 0-15), higher scores indicate higher level of frailty.
Time Frame
10 years
Title
Patient reported outcomes - satisfaction with cosmesis
Description
Satisfaction with cosmesis (questionnaire by Sneeuw et al. and BREAST-Q)). The questionnaire by Sneeuw et al. consists of seven questions, no total score is calculated. These questions are about difference between the treated and untreated breast in terms of size, shape, skin color, firmness and overall cosmesis (scale: no difference, small difference, moderate difference, large difference), visibility of the surgical scar (scale: not distracting, little distracting, quite distracting, very distracting) and satisfaction with the appearance of the treated breast (scale: very satisfied, satisfied, not unsatisfied, unsatisfied, very unsatisfied). No total score is calculated. From the BREAST-Q questionnaire only the postoperative domain of satisfaction with the breasts is used (scale 0-100), higher scores indicate more satisfaction.
Time Frame
10 years
Title
Local, regional and distant relapse rate
Description
Recurrences up to 10 years following radiotherapy will be evaluated.
Time Frame
10 years
Title
Disease free survival
Description
Disease free survival will be evaluated as the interval between treatment and first date of recurrence of disease.
Time Frame
10 years
Title
Overall survival
Description
Overall survival will be evaluated as interval between treatment and death.
Time Frame
10 years
Title
Tumor infiltrating lymphocytes
Description
The presence of tumor infiltrating lymphocytes in the tumor will be assessed at baseline (using the diagnostic biopsy) and following treatment (using the surgical resection). This will be correlated to the pathologic response.
Time Frame
up to 12 months
Title
Circulating tumor DNA
Description
Patients will be evaluated for the presence of circulating tumor DNA at baseline and following radiotherapy. This will be correlated to the pathologic response.
Time Frame
up to 12 months
Other Pre-specified Outcome Measures:
Title
Dosimetry of radiotherapy in prone position
Description
Patient can undergo an additional MRI in prone position for a radiotherapy planning study
Time Frame
1 month

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: WHO performance scale ≤2. Females at least 50 years of age with unifocal cT1N0 breast cancer or females at least 70 years of age with unifocal cT1-2(maximum 3 cm)N0 breast cancer on mammography, ultrasound and MRI. Patients with an indication for chemotherapy or immunotherapy according to Dutch National Oncoline Guidelines or own hospital protocols are not eligible. Patients with an indication for endocrine therapy are eligible. Tumor size as assessed on MRI. On tumor biopsy: Bloom-Richardson grade 1 or 2. Non-lobular invasive histological type carcinoma. LCIS or (non-extensive) DCIS is accepted. ER positive tumor receptor. HER2 negative tumor. Tumor-negative sentinel node. Adequate communication and understanding skills of the Dutch language. Exclusion Criteria: Legal incapacity. BRCA1, BRCA2 or CHEK2 gene mutation. Previous history of breast cancer or DCIS. Other type of malignancy within 5 years before breast cancer diagnosis. Patients with adequately treated malignancy longer than 5 years before breast cancer diagnosis are eligible for inclusion. For adequately treated carcinoma in situ of the cervix or basal cell carcinoma of the skin no specific time span to breast cancer diagnosis is required for inclusion. Collagen synthesis disease. Signs of extensive DCIS component on histological biopsy or imaging. Invasive lobular carcinoma. MRI absolute contraindications as defined by the Department of Radiology. Nodal involvement with cytological or histological confirmation. Indication for treatment with (neo-)adjuvant chemotherapy. Non-feasible dosimetric RT plan.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Desiree van den Bongard, MD PhD
Organizational Affiliation
UMC Utrecht
Official's Role
Principal Investigator
Facility Information:
Facility Name
UMC Utrecht
City
Utrecht
Country
Netherlands

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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MRI-guided Single Dose Preoperative Radiotherapy in Low-risk Breast Cancer

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