脳転移に対するRAPid SimPLE標的放射線治療 (RAPPLE)
脳転移に対する5日間RAPid SimPLE（RAPPLE）標的放射線治療と1日間RAPid SimPLE（RAPPLE）の無作為化第II相非劣性研究
The aim of the study is to show that rapid, simple targeted radiotherapy to brain metastases with 8 Gy / 1 is non-inferior to 20 Gy / 5 in terms of overall survival for patients with poor prognosis.
調査の概要
詳細な説明
Hypothesis For selected patients with limited life expectancy, a single targeted fraction of 8 Gy / 1 to brain metastases will provide equivalent survival as targeted radiotherapy with 20 Gy / 5 to brain metastases.
Justification The QUARTZ study randomized patients with brain metastases and poor prognosis between 20 Gy / 5 whole brain radiotherapy (WBRT) and best supportive care. The median survival in both arms of the study was 9 weeks. The quality of life in both arm was also the same. It is known that WBRT significantly diminishes quality of life. The investigators interpretation of the QUARTZ trial is that the unchecked growth of brain metastases in the best supportive care arm diminishes quality of life as much as WBRT. To control brain metastases without giving WBRT, targeted treatment with 20 Gy / 5 to the metastases alone is standard care at BC Cancer. Numerous randomized trials have compared the efficacy of 20-30 Gy / 5-10 fractions and 8 Gy / 1 for palliative treatment of pain from bone metastases. In addition, there is a randomized trial showing that 20 Gy / 5 and 8 Gy /1 are equally effective for the treatment of symptoms from spinal cord compression. This study will test the use of this shorter, one-visit treatment schedule against the standard 5-visit treatment schedule for patients with brain metastases.
Research Design Randomized Phase II Non-Inferiority Study. The estimated median survival for this cohort, based upon a prior cohort study from 2012-2016 at BC Cancer is 3 months (13 weeks). The investigators would regard a study median survival of less than the 9-week median survival observed in the QUARTZ trial as unacceptable. Hence, the hazard ratio for the experimental arm and the control arm is: 13 weeks / 9 weeks = 1.44. With one-sided Type I error set at alpha = 0.2 and power = 0.8, the investigators calculated a theoretical sample size of 86 patients. Based on prior experience with clinical trials for patients with brain metastases, a 15% risk of drop-out and loss to follow up is expected. Hence the final sample size will be 100 patients. Stratification by the diagnosis-specific graded prognostic assessment (DS-GPA) ranges of 0.0 - 1.0 and 1.5 - 2.0 and lung cancer versus other histologies will help to ensure baseline characteristics that predict for equal survival are equally distributed in both arms of the study.
Statistical Analysis The primary endpoint is overall survival. The study will be considered to be a positive phase II non-inferiority study if the median survival in the experimental arm is within 4 weeks of the median survival in the standard arm.
研究の種類
入学 (推定)
段階
- フェーズ2
連絡先と場所
研究場所
-
-
British Columbia
-
Abbotsford British Columbia、British Columbia、カナダ
- BC Cancer - Abbotsford
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Kelowna、British Columbia、カナダ、V1Y5L3
- BC Cancer - Kelowna
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Prince George、British Columbia、カナダ、V2M7E9
- BC Cancer - Prince George
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Surrey、British Columbia、カナダ
- BC Cancer - Surrey
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Vancouver、British Columbia、カナダ、V5Z 4E6
- BC Cancer - Vancouver
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Victoria、British Columbia、カナダ
- BC Cancer - Victoria
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
Patients must fulfil all the following criteria to be eligible for admission to the study:
- Age ≥ 18
- Pathological diagnosis of a non-hematopoietic malignancy
- Brain metastases of any size
- Any number of untreated or progressing, previously treated brain metastases that can all be contoured and targeted
- Presence of extracranial disease
- Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) ≤ 2.0 (https://brainmetgpa.com/) or Graded Prognostic Assessment ≤ 2.0 (Appendix I)
- Able to complete the EuroQOL (EQ-5D-5L) questionnaire
- Willing and able to have regular imaging follow up
- Feasible to start protocol treatment within 14 calendar days of participant enrolment
- Karnofsky Performance Score (KPS) ≥ 50
Exclusion Criteria
Patients who fulfill any of the following criteria are not eligible for admission to the study:
- Inability to have a brain MRI.
- WBRT less than 3 months prior to randomization
- Disseminated leptomeningeal carcinomatosis (limited pachymeningeal disease is permitted)
- Multiple sclerosis
- Neurologically declining despite corticosteroids
- Appropriate for surgery or stereotactic radiosurgery
- Germ cell and primary brain tumours
- Systemic lupus erythematosis, scleroderma, or other connective tissue disorders not in remission
- Any other serious intercurrent illness or medical condition judged by the local investigator to compromise the patient's safety, preclude safe administration of the planned protocol treatment, or prevent the patient from being managed according to the protocol guidelines
- Pregnancy
- Potentially fertile men or women of childbearing potential who are unwilling to employ highly effective contraception
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 |
|---|---|
|
アクティブコンパレータ：20 Gy in 5 Fractions Volumetric Modulated Arc Therapy to Brain Metastases
Five treatments of 4 Gy will be delivered using volumetric modulated arc therapy on a conventional linear accelerator in a conventional head shell without the use of stereotactic radiosurgery technique. |
Volumetric Modulated Arc Therapy |
|
実験的：8 Gy in 1 Fraction Volumetric Modulated Arc Therapy to Brain Metastases
A single treatment of 8 Gy will be delivered using volumetric modulated arc therapy on a conventional linear accelerator in a conventional head shell without the use of stereotactic radiosurgery technique. |
Volumetric Modulated Arc Therapy |
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 |
|---|---|---|
|
Survival Time
時間枠：1 year
|
The median time from randomization to death |
1 year
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Median Time to Decline in Karnofsky Performance Status
時間枠：1 year
|
The time from randomization to a 20-point decline in Karnofsky Performance Status |
1 year
|
|
Control of treated brain metastases
時間枠：1 year
|
Cumulative incidence of local recurrence of treated metastases |
1 year
|
|
Corticosteroid use
時間枠：6 weeks
|
Proportion of patients taking corticosteroids |
6 weeks
|
|
Control of brain disease
時間枠：1 year
|
Cumulative incidence of (local recurrence of treated metastases OR new metastases) |
1 year
|
|
Retreatments for brain metastases
時間枠：1 year
|
Proportion of patients with retreatment for brain metastases after radiotherapy |
1 year
|
|
Adverse Events
時間枠：1 year
|
Cumulative incidence of adverse events, graded using CTCAE Version 5.0 |
1 year
|
|
Health-Related Quality of Life
時間枠：1 year
|
Median time to a minimum clinically important decline in Health-Related Quality of Life |
1 year
|
協力者と研究者
捜査官
- 主任研究者：Alan Nichol, MD、BC Cancer Vancouver
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 (推定)
研究の完了 (推定)
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
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