Ultrahypofractionated Versus Normofractionated Sequential Boost After Whole-breast Radiation Therapy in Patients Treated With Breast-conserving Surgery for Breast Cancer (ULTIMO)
The ULTIMO trial is a monocentric, prospective, randomised controlled, open-label, phase III interventional clinical trial, with a non-inferiority design, in patients with breast cancer undergoing breast conservative treatment (BCT). After giving informed consent and verifying eligibility, data collection starts and patients will be randomized in one of the following treatment arms:
- Standard treatment arm: Breast Conserving Surgery (BCS) takes place, followed by the SoC hypofractionated Whole Breast Radiation Therapy (WBRT) and SoC normofractioned sequential boost (normSEB) of 10Gy over 5 fractions.
- Experimental treatment arm: Breast Conserving Surgery (BCS) takes place, followed by the SoC hypofractionated WBRT and experimental ultrahypofractionated sequential boost (ultSEB) of 6Gy in a single fraction.
The primary objective of the ULTIMO study is to assess whether the ultSEB RT boost protocol is non-inferior to the current SoC normSEB RT boost protocol. This assessment will be based on the cosmetic outcome of the breasts, while also taking into account quality of life (QoL), the frequency and intensity of (S)AEs of interest (breast pain and fibrosis), and oncological survival.
調査の概要
状態
条件
研究の種類
入学 (実際)
段階
- フェーズ 3
連絡先と場所
研究場所
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Antwerpen
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Antwerp、Antwerpen、ベルギー、2610
- Ziekenhuis aan de Stroom
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参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- Breast cancer patients referred for WBRT + boost to the lumpectomy cavity
- Patients ≥18y
- Karnofsky Performance Score >70%, or ECOG <2
- Life expectancy of more than 5 years
- Invasive tumour free resection margins, defined as R0 resection on the pathology report
- Written informed consent
Exclusion Criteria:
- Previous contralateral breast cancer
- Previous RT of the same breast or thorax.
- Metastatic disease (M1)
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
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アクティブコンパレータ：Standard treatment arm (SoC; Normofractionated boost RT)
In the control arm, the boost of the radiation therapy will be delivered according to the standard of care fractionation and dosage scheme. This consists of 5 fractions of 2Gy each, adding up to a total dose of 10Gy. All other treatments are not considered to be study-specific and are performed according to the standard of care treatment for breast cancer. |
Standard of care fractionation and dosage scheme of the sequential radiation therapy boost.
This consists of 5 fractions of 2Gy each, adding up to a total dose of 10Gy.
他の名前：
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実験的：Experimental treatment arm (Hypofractionated boost RT)
In the experimental arm, the boost of the radiation therapy is delivered in a ultrahypofractionated scheme. This consists of a single fraction of 6Gy. All other treatments are not considered to be study-specific and are performed according to the standard of care treatment for breast cancer. |
The radiation therapy sequential boost is delivered in a ultrahypofractionated scheme.
This consists of a single fraction of 6Gy.
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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Cosmetic non-inferiority - BCCT.core scoring
時間枠：From enrollment to the end of follow-up at 3 years of follow-up, counting from the last study visit.
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Operationalisation: BCCT.core is a software package for evaluating photographs of breasts after BCS. The 'Global cosmetic result' from the two frontal photos (arms up, and arms down) will be averaged and then used as the individual value of this measure. The results are scored on a 4-point Likert scale, coded as 0-3. Analysis metric: The change from baseline at 1 and 3YFU will be used. Negative values will be transformed to '1' to signal an inferiority event, positive or values of zero will be transformed to '0' to signal non-inferiority. For comparisons and estimands, please refer to the SAP. Method of aggregation: The results will be reported as a contingency table reporting both frequencies and proportions of non-inferior and inferior results in each treatment arm. Time point(s): A baseline assessment is performed during the screening visit, followed by repeated measurements during the 1 and 3YFU (primary endpoint) visits. |
From enrollment to the end of follow-up at 3 years of follow-up, counting from the last study visit.
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Cosmetic outcome - Expert panel, AIS-TAS
時間枠：From enrollment to the end of follow-up at 3 years of follow-up, counting from the last study visit.
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Operationalisation: The AIS is a tool for scoring breast cosmesis based on standardized photos. It comprises of 5 items, each comprising of a 5 point Likert-scale, coded as 1 to 5. The score is given based on the group of photos taken at a single time point. The scores of all items are summed to produce the TAS, which consequently ranges from 5 to 25. The AIS is used in an expert panel setting, where all scores, from each assessor are averaged per item. A higher scores represents a more favourable cosmetic outcome. Analysis metric: AIS-TAS absolute values will be used for analysis. Method of aggregation: The mean, median, SD and IQR will be reported. For comparisons and estimands, please refer to the SAP. Time point(s): A baseline assessment is performed during the screening visit, followed by repeated measurements during the 1 and 3YFU (primary endpoint) visits. |
From enrollment to the end of follow-up at 3 years of follow-up, counting from the last study visit.
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Cosmetic outcome - Expert panel, AIS-Symmetry
時間枠：From enrollment to the end of follow-up at 3 years of follow-up, counting from the last study visit.
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Operationalisation: The AIS is a tool for scoring breast cosmesis based on standardized photographs. It comprises of 5 items, each comprising of a 5 point Likert-scale, coded as 1 to 5. The score is given based on the group of photos taken at a single time point. The AIS is used in an expert panel setting, where all scores, from each assessor are averaged per item. A higher scores represents a more favourable cosmetic outcome. Analysis metric: AIS-Symmetry score absolute values will be used for analysis. Method of aggregation: The mean, median, SD and IQR will be reported. For comparisons and estimands, please refer to the SAP. Time point(s): A baseline assessment is performed during the screening visit, followed by repeated measurements during the 1 and 3YFU (primary endpoint) visits. |
From enrollment to the end of follow-up at 3 years of follow-up, counting from the last study visit.
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Cosmetic outcome - Physician scoring
時間枠：From enrollment to the end of follow-up at 3 years of follow-up, counting from the last study visit.
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Operationalisation: The physician scoring scale (questionnaire, cfr. protocol) will be used to assess cosmetic outcome. The normalised average score of all items will be summed and used as outcome measure. This will be calculated as the score of an item divided by the amount of answering options minus 1 (k-1), averaged over all items. Some questions have the option 'not evaluable', if this answer is selected, then that item is not used in deriving the average score. A higher scores represents a more favourable cosmetic outcome. Analysis metric: Absolute values will be used for analysis. Method of aggregation: The mean, median, SD and IQR will be reported. For comparisons and estimands, please refer to the SAP. Time point(s): A baseline assessment is performed during the screening visit. It is then assessed again at 1 year, and 3 years of follow-up after the last study treatment (LST). |
From enrollment to the end of follow-up at 3 years of follow-up, counting from the last study visit.
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Cosmetic outcome - Patient reported (PROM)
時間枠：From enrollment to the end of follow-up at 3 years of follow-up, counting from the last study visit.
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Operationalisation: The cosmetic evaluation questionnaire by Sneeuw at al. will be used to assess cosmetic outcome, as reported by the participant. The normalised average score of all items will be summed and used as outcome measure. This will be calculated as the score of an item divided by the amount of answering options minus 1 (k-1), averaged over all items. A higher scores represents a more favourable cosmetic outcome. Analysis metric: Absolute values (calculated score) will be used for analysis. Method of aggregation: The mean, median, variance and IQR will be reported. For comparisons and estimands, please refer to the SAP. Time point(s): A baseline assessment is performed during the screening visit. It is then assessed again at 1 year, and 3 years of follow-up after the last study treatment (LST). |
From enrollment to the end of follow-up at 3 years of follow-up, counting from the last study visit.
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Quality of life - EORTC QLQ C30 v3 - Global health status/QoL
時間枠：From enrollment to the end of follow-up at 3 years of follow-up, counting from the last study visit.
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Operationalisation: The QoL (QLQ-C30) outcome variable is operationalised through the QLQ-C30 questionnaire. The answers are transformed into 3 separate scores, which can all range from 0 to 100. These scores are: Global health status/QoL, Functional scales, Symptom scales. Where a higher score on the first 2 scales indicate a better health state and QoL, while on the symptom scale a higher score indicates a higher level of disturbance by symptoms. Analysis metric: The QLQ-C30 Global health status absolute values will be used for analysis. Method of aggregation: The mean, median, SD and IQR will be reported. For comparisons and estimands, please refer to the SAP. Time point(s): A baseline assessment is performed during the screening visit. It is then assessed again at 1 year, and 3 years of follow-up after the last study treatment (LST). |
From enrollment to the end of follow-up at 3 years of follow-up, counting from the last study visit.
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Quality of life - EORTC QLQ C30 v3 -Functional scales
時間枠：From enrollment to the end of follow-up at 3 years of follow-up, counting from the last study visit.
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Operationalisation: The QoL (QLQ-C30) outcome variable is operationalised through the QLQ-C30 questionnaire. The answers are transformed into 3 separate scores, which can all range from 0 to 100. These scores are: Global health status/QoL, Functional scales, Symptom scales. Where a higher score on the first 2 scales indicate a better health state and QoL, while on the symptom scale a higher score indicates a higher level of disturbance by symptoms. Analysis metric: The QLQ-C30 Functional scales score absolute values will be used for analysis. Method of aggregation: The mean, median, SD and IQR will be reported. For comparisons and estimands, please refer to the SAP. Time point(s): A baseline assessment is performed during the screening visit. It is then assessed again at 1 year, and 3 years of follow-up after the last study treatment (LST). |
From enrollment to the end of follow-up at 3 years of follow-up, counting from the last study visit.
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Quality of life - EORTC QLQ C30 v3 -Symptom scales
時間枠：From enrollment to the end of follow-up at 3 years of follow-up, counting from the last study visit.
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Operationalisation: The QoL (QLQ-C30) outcome variable is operationalised through the QLQ-C30 questionnaire. The answers are transformed into 3 separate scores, which can all range from 0 to 100. These scores are: Global health status/QoL, Functional scales, Symptom scales. Where a higher score on the first 2 scales indicate a better health state and QoL, while on the symptom scale a higher score indicates a higher level of disturbance by symptoms. Analysis metric: The QLQ-C30 Symptom scales score absolute values will be used for analysis. Method of aggregation: The mean, median, SD and IQR will be reported. For comparisons and estimands, please refer to the SAP. Time point(s): A baseline assessment is performed during the screening visit. It is then assessed again at 1 year, and 3 years of follow-up after the last study treatment (LST). |
From enrollment to the end of follow-up at 3 years of follow-up, counting from the last study visit.
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Quality of life - EORTC QLQ BR23 v1 - Functional scales
時間枠：From enrollment to the end of follow-up at 3 years of follow-up, counting from the last study visit.
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Operationalisation: The QoL (QLQ-BR23) outcome variable is operationalised through the QLQ-BR23 questionnaire. The answers are transformed into 2 separate scores, which can both range from 0 to 100. These scores are: Functional scales; Symptom scales. Where a higher score on the functional scale indicate a better health state and QoL, while on the symptom scale a higher score indicates a higher level of disturbance by symptoms. Analysis metric: The QLQ-BR23 Functional scales score absolute values will be used for analysis. Method of aggregation: The mean, median, SD and IQR will be reported. For comparisons and estimands, please refer to the SAP. Time point(s): A baseline assessment is performed during the screening visit. It is then assessed again at 1 year, and 3 years of follow-up after the last study treatment (LST). |
From enrollment to the end of follow-up at 3 years of follow-up, counting from the last study visit.
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Quality of life - EORTC QLQ BR23 v1 - Symptom scales
時間枠：From enrollment to the end of follow-up at 3 years of follow-up, counting from the last study visit.
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Operationalisation: The QoL (QLQ-BR23) outcome variable is operationalised through the QLQ-BR23 questionnaire. The answers are transformed into 2 separate scores, which can both range from 0 to 100. These scores are: Functional scales; Symptom scales. Where a higher score on the functional scale indicate a better health state and QoL, while on the symptom scale a higher score indicates a higher level of disturbance by symptoms. Analysis metric: The QLQ-BR23 Symptom scales score absolute values will be used for analysis. Method of aggregation: The mean, median, SD and IQR will be reported. For comparisons and estimands, please refer to the SAP. Time point(s): A baseline assessment is performed during the screening visit. It is then assessed again at 1 year, and 3 years of follow-up after the last study treatment (LST). |
From enrollment to the end of follow-up at 3 years of follow-up, counting from the last study visit.
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Fibrosis
時間枠：From enrollment to the end of follow-up at 3 years of follow-up, counting from the last study visit.
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Operationalisation: During the 1Y and 3Y Follow-Up study visits the overall and tumour bed fibrosis will be scored according to the 'National Cancer Institute Common Terminology Criteria for Adverse Events' (NCI-CTCAE) v5.0 AE reporting system. This scoring will be performed by either the principal- or sub-investigators. Analysis metric: Tabulation of absence vs. presence and severity of fibrosis will be used for analysis. Method of aggregation: The proportion of participants experiencing no 'Fibrosis' vs. any 'Fibrosis' will be used. As well as the frequency of all grades, including 0 (absence). For comparisons and estimands, please refer to the SAP. Time point(s): Fibrosis will be assessed and recorded during the 1YFU and 3YFU study visits. |
From enrollment to the end of follow-up at 3 years of follow-up, counting from the last study visit.
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Breast pain
時間枠：From enrollment to the end of follow-up at 3 years of follow-up, counting from the last study visit.
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Operationalisation: During the 1Y and 3Y Follow-Up study visits the occurrence of 'Breast pain' will be scored according to the 'National Cancer Institute Common Terminology Criteria for Adverse Events' (NCI-CTCAE) v5.0 AE reporting system. This scoring will be performed by either the principal- or sub-investigators. Analysis metric: Tabulation of absence vs. presence and severity of 'Breast pain' will be used for analysis. Method of aggregation: The proportion of participants experiencing no 'Breast pain' vs. any 'Breast pain' will be used. As well as the frequency of all grades, including 0 (absence). For comparisons and estimands, please refer to the SAP. Time point(s): Fibrosis will be assessed and recorded during the 1YFU and 3YFU study visits. |
From enrollment to the end of follow-up at 3 years of follow-up, counting from the last study visit.
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Oncological survival and time-to-event data - Overall Survival (OS)
時間枠：Oncological TTE data will be registered at 1 and 3 years of follow-up after the last study treatment (LST). However, the exact dates of diagnosis/death will be used.
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Operationalisation: The oncological survival and TTE data are operationalised as time-to-event intervals for the events of interest listed below. The 'OS' TTE/survival outcome will be reported according to the 2015 DATECAN consensus, including time-to-event data for the following events of interest: 'Death from any cause'. Analysis metric: The TTE data is registered in days from randomisation (Rz). Censoring will be used for participants without events at the end of their follow up. Method of aggregation: KM-estimates, as well as proportions free from events at follow-up visit timepoints will be reported. The non-aggregated data will be used for survival analysis. For comparisons and estimands, please refer to the SAP. |
Oncological TTE data will be registered at 1 and 3 years of follow-up after the last study treatment (LST). However, the exact dates of diagnosis/death will be used.
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Oncological survival and time-to-event data - Breast Cancer-Specific Survival (BCSS)
時間枠：Oncological TTE data will be registered at 1 and 3 years of follow-up after the last study treatment (LST). However, the exact dates of diagnosis/death will be used.
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Operationalisation: The oncological survival and TTE data are operationalised as time-to-event intervals for the events of interest listed below. The 'BCSS' TTE/survival outcome will be reported according to the 2015 DATECAN consensus, including time-to-event data for the following events of interest: 'Death from breast cancer'. Analysis metric: The TTE data is registered in days from randomisation (Rz). Censoring will be used for participants without events at the end of their follow up. Method of aggregation: KM-estimates, as well as proportions free from events at follow-up visit timepoints will be reported. The non-aggregated data will be used for survival analysis. For comparisons and estimands, please refer to the SAP. |
Oncological TTE data will be registered at 1 and 3 years of follow-up after the last study treatment (LST). However, the exact dates of diagnosis/death will be used.
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Oncological survival and time-to-event data - Relapse-Free Survival (RFS)
時間枠：Oncological TTE data will be registered at 1 and 3 years of follow-up after the last study treatment (LST). However, the exact dates of diagnosis/death will be used.
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Operationalisation: The oncological survival and TTE data are operationalised as time-to-event intervals for the events of interest listed below. The 'RFS' TTE/survival outcome will be reported according to the 2015 DATECAN consensus, including time-to-event data for the following events of interest: 'Death from any cause', 'Invasive ipsilateral breast tumor recurrence', 'Local Invasive recurrence', 'Regional Invasive recurrence', 'occurrence of metastases', or 'Ipsilateral DCIS'. Analysis metric: The TTE data is registered in days from randomisation (Rz). Censoring will be used for participants without events at the end of their follow up. Method of aggregation: KM-estimates, as well as proportions free from events at follow-up visit timepoints will be reported. The non-aggregated data will be used for survival analysis. For comparisons and estimands, please refer to the SAP. |
Oncological TTE data will be registered at 1 and 3 years of follow-up after the last study treatment (LST). However, the exact dates of diagnosis/death will be used.
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Oncological survival and time-to-event data - Locoregional Relapse-Free Survival (L-RFS)
時間枠：Oncological TTE data will be registered at 1 and 3 years of follow-up after the last study treatment (LST). However, the exact dates of diagnosis/death will be used.
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Operationalisation: The oncological survival and TTE data are operationalised as time-to-event intervals for the events of interest listed below. The 'L-RFS' TTE/survival outcome will be reported according to the 2015 DATECAN consensus, including time-to-event data for the following events of interest: 'Death from any cause', 'Invasive ipsilateral breast tumor recurrence', 'Local Invasive recurrence', 'Regional Invasive recurrence', or 'Ipsilateral DCIS'. Analysis metric: The TTE data is registered in days from randomisation (Rz). Censoring will be used for participants without events at the end of their follow up. Method of aggregation: KM-estimates, as well as proportions free from events at follow-up visit timepoints will be reported. The non-aggregated data will be used for survival analysis. For comparisons and estimands, please refer to the SAP. |
Oncological TTE data will be registered at 1 and 3 years of follow-up after the last study treatment (LST). However, the exact dates of diagnosis/death will be used.
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Oncological survival and time-to-event data - Distant-Relapse Free Survival (D-RFS)
時間枠：Oncological TTE data will be registered at 1 and 3 years of follow-up after the last study treatment (LST). However, the exact dates of diagnosis/death will be used.
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Operationalisation: The oncological survival and TTE data are operationalised as time-to-event intervals for the events of interest listed below. The 'D-RFS' TTE/survival outcome will be reported according to the 2015 DATECAN consensus, including time-to-event data for the following events of interest: 'Death from any cause', or 'occurrence of metastases'. Analysis metric: The TTE data is registered in days from randomisation (Rz). Censoring will be used for participants without events at the end of their follow up. Method of aggregation: KM-estimates, as well as proportions free from events at follow-up visit timepoints will be reported. The non-aggregated data will be used for survival analysis. For comparisons and estimands, please refer to the SAP. |
Oncological TTE data will be registered at 1 and 3 years of follow-up after the last study treatment (LST). However, the exact dates of diagnosis/death will be used.
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協力者と研究者
スポンサー
捜査官
- 主任研究者：Melanie Machiels, MD, PhD、Iridium Netwerk
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- CTO21030GZA
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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