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

• ClinicalTrials.gov Identifier: NCT03863301
• Recruitment Status: Withdrawn
• First Posted: March 5, 2019
• Last Update Posted: February 26, 2021
• Sponsor: UMC Utrecht
• Information provided by (Responsible Party): HJGD van den Bongard, UMC Utrecht

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.

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Radiation: MR-guided single dose preoperative PBI	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Single arm interventional cohort study
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: MRI-guided Single Dose Preoperative Radiotherapy in Low-risk Breast Cancer
• Estimated Study Start Date: March 4, 2019
• Estimated Primary Completion Date: November 2022
• Estimated Study Completion Date: November 2031

Arms and Interventions

Arm	Intervention/treatment
Experimental: MR-guided single dose preoperative PBI	Radiation: MR-guided single dose preoperative PBI; A single dose of 20Gy to the gross tumor volume (GTV) is prescribed, to the clinical target volume (GTV + 20mm margin) 15Gy is prescribed.

Outcome Measures

Primary Outcome Measures :

1. Pathologic complete response (pCR) [ Time Frame: up to 12 months ]
   pCR is assessed 6 or 12 months following single dose radiotherapy. Patients will undergo breast-conserving surgery.

Secondary Outcome Measures :

1. Radiologic response on MRI [ Time Frame: up to 12 months ]
   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.
2. Biopsy of irradiated tumor [ Time Frame: up to 12 months ]
   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.
3. Treatment-induced toxicity [ Time Frame: 10 years ]
   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.
4. Patient reported outcomes - quality of life [ Time Frame: 10 years ]

   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.

5. Patient reported outcomes - quality of life [ Time Frame: 10 years ]

   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.

6. Patient reported outcomes - anxiety and depression [ Time Frame: 10 years ]
   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.
7. Patient reported outcomes - fatigue [ Time Frame: 10 years ]
   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.
8. Patient reported outcomes - work ability [ Time Frame: 10 years ]
   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.
9. Patient reported outcomes - frailty [ Time Frame: 10 years ]
   Frailty (Groningen Frailty Indicator), one dimension (scale 0-15), higher scores indicate higher level of frailty.
10. Patient reported outcomes - satisfaction with cosmesis [ Time Frame: 10 years ]

    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.

11. Local, regional and distant relapse rate [ Time Frame: 10 years ]
    Recurrences up to 10 years following radiotherapy will be evaluated.
12. Disease free survival [ Time Frame: 10 years ]
    Disease free survival will be evaluated as the interval between treatment and first date of recurrence of disease.
13. Overall survival [ Time Frame: 10 years ]
    Overall survival will be evaluated as interval between treatment and death.
14. Tumor infiltrating lymphocytes [ Time Frame: up to 12 months ]
    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.
15. Circulating tumor DNA [ Time Frame: up to 12 months ]
    Patients will be evaluated for the presence of circulating tumor DNA at baseline and following radiotherapy. This will be correlated to the pathologic response.

Other Outcome Measures:

1. Dosimetry of radiotherapy in prone position [ Time Frame: 1 month ]
   Patient can undergo an additional MRI in prone position for a radiotherapy planning study

Eligibility Criteria

• Ages Eligible for Study: 50 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

Netherlands

UMC Utrecht

Utrecht, Netherlands

Sponsors and Collaborators

UMC Utrecht

Investigators

• Principal Investigator: Desiree van den Bongard, MD PhD; UMC Utrecht

More Information

• Responsible Party: HJGD van den Bongard, Principal Investigator, UMC Utrecht
• ClinicalTrials.gov Identifier: NCT03863301
• Other Study ID Numbers: NL63209 041 18
• First Posted: March 5, 2019
• Last Update Posted: February 26, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

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

Keywords provided by HJGD van den Bongard, UMC Utrecht:

Radiotherapy

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases