Optimal irradiation intervals in stereotactic radiotherapy for patients with brain metastases
| ISRCTN | ISRCTN15950448 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15950448 |
| Secondary identifying numbers | UMIN000048728 |
- Submission date
- 22/11/2022
- Registration date
- 23/11/2022
- Last edited
- 23/11/2022
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English summary of protocol
Background and study aims
Radiobiological daily changes within tumors are considered to be quite different between stereotactic radiotherapy (SRT) (e.g., 50 Gy in 4 fractions) and conventional radiotherapy (e.g., 60 Gy in 30 fractions). Most tumors have hypoxic tumor cells which are radioresistant and can cause a recurrence after radiotherapy. During the period of daily irradiation, surviving hypoxic cells within tumor reoxygenate and get more sensitive to successive irradiation. From the data of radiobiological basic experiments, we consider that reoxygenation continues more than three days after single high-dose irradiation. We think that longer intervals more than 24-hour may be necessary to allow more reoxygenation to occur and enhance therapeutic efficacy of SRT. We aim to assess the optimal interval of irradiation in SRT and compare outcomes of daily irradiation with irradiation at two- to three-day intervals in SRT for patients with one to five brain metastases.
Who can participate?
Patients aged 20 or older with one to five brain metastases, less than 3.0 cm diameter, and Karnofsky Performance Status greater than or equal to 70.
What does the study involve?
A total of 70 eligible patients will be enrolled. After stratifying by the number of brain metastases (1, 2 vs. 3–5) and diameter of the largest tumor (<2 cm vs. ≥2 cm), we randomly assigned patients (1:1) to receive daily irradiation (Arm 1), or irradiation at two- to three-day intervals (Arm 2). Both arms are performed with total dose of 27-30 Gy in 3 fractions.
What are the possible benefits and risks of participating?
No particular benefit is expected from participating in this clinical trial. With regards to risks of participating, mini mental status examination (MMSE) needs to be evaluated every 6 months after SRT.
Where is the study run from?
Participating institutions will be six academic and four general hospitals in Japan. One of the participating institutions is Nagoya City University Hospital (Japan), and the Principal Investigator, Dr Natsuo Tomita is based there. In each participating institution, the institutional review board will approve the protocol before patient enrollment occurred.
When is the study starting and how long is it expected to run for?
August 2022 to September 2028
Who is funding the study?
Hori Science and Arts Foundation (Japan)
Grant-in-aid for research on radiation oncology of JASTRO 2021-2022 (Japan)
Japan Society for the Promotion of Science (JSPS) KAKENHI
Who is the main contact?
Dr Natsuo Tomita, c051728@yahoo.co.jp
Contact information
Principal Investigator
1 Kawasumi
Mizuho-cho
Mizuho-ku
Nagoya
4678601
Japan
 ORCID ID |
0000-0003-4601-0119 |
|---|---|
| Phone | +81 52-853-8276 |
| c051728@yahoo.co.jp |
Study information
| Study design | Multicenter open-label randomized phase II trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet. |
| Scientific title | Daily irradiation versus irradiation at two- to three-day intervals in stereotactic radiotherapy for patients with 1-5 brain metastases: a multicenter randomized phase II trial |
| Study objectives | Local control is superior in irradiation at two- to three-day intervals than in daily irradiation Iin stereotactic radiotherapy for patients with one to five brain metastases. |
| Ethics approval(s) | Approved 02/08/2022, IRB of Nagoya City University Graduate School of Medical Sciences (Nagoya City University Hospital, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan; no telephone number provided; irb_jimu@med.nagoya-cu.ac.jp), ref: 46-22-0004 |
| Health condition(s) or problem(s) studied | One to five brain metastases with less than 3.0 cm diameter. |
| Intervention | In stereotactic radiotherapy (SRT) of 27-30 Gy in three fractions for patients with one to five brain metastases with less than 3.0 cm diameter, daily irradiation is used in the standard arm while irradiation at two- to three-day intervals is performed in the experimental arm. Both arms are performed daily with a total dose of 27-30 Gy in 3 fractions (9-10 Gy per fraction). Arm 1 (standard arm): consecutive daily irradiation; total SRT duration, 3 days. Arm 2 (experimental arm): irradiation at two- to three-day intervals; total SRT duration, 8 days. The study will employ a 1:1 randomization between Arm 1 (consecutive daily irradiation) and Arm 2 (irradiation at two- to three-day intervals). Patients will be stratified by (1) maximum diameter (≤ 2 cm vs. > 2 cm) among their brain metastases and (2) number of brain metastases (1, 2 vs. 3-5). Random assignment of treatment groups is centrally managed using the web-based system of Mujinwari (Iruka System Ltd., Tokyo, Japan). |
| Intervention type | Procedure/Surgery |
| Primary outcome measure | Intracranial local control rate (IC-LC), defined as intracranial local control at initially treated sites at 12 months |
| Secondary outcome measures | 1. Intracranial progression-free survival (IC-PFS), defined as intracranial PFS at initially treated and new sites at 12 months (and 6 and 24 months). 2. Overall survival (OS), defined as the time from the date of randomization to death from any cause at 12 months (and 6 and 24 months). 3. Toxicity, assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 at 12 months (and 3 and 24 months). 4. Non-worsening of Karnofsky performance status (KPS), defined as the time from randomization to decline of KPS from any cause. 5. Non-worsening of mini mental status examination (MMSE), defined as the time from randomization to decline of MMSE from any cause. |
| Overall study start date | 02/08/2022 |
| Completion date | 01/09/2028 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 20 Years |
| Sex | Both |
| Target number of participants | 70 |
| Key inclusion criteria | 1. Age 20 years or older. 2. Karnofsky Performance Status (KPS) > or = 70. 3. Total number of 1-5 brain metastases by enhanced magnetic resonance imaging (MRI). 4. Brain metastases with less than 3.0 cm diameter by enhanced magnetic resonance imaging (MRI). 5. Willing to provide informed consent. |
| Key exclusion criteria | 1. Histological type of the primary site is lymphoma, small cell lung cancer, and germ cell tumor. 2. Metastases of the brainstem. 3. Meningeal carcinomatosis. 4. History of whole brain radiation therapy (WBRT) or substantial overlap with a previously treated radiation volume. 5. Surgical history for BM. 6. Difficult to be enrolled to the study by reason of insanity. 7. Inability to use enhancing agent for MRI due to low renal function or allergy. 8. In pregnancy or with expectation of pregnancy 9. Physician dismiss as subject of the study. |
| Date of first enrolment | 01/09/2022 |
| Date of final enrolment | 31/03/2026 |
Locations
Countries of recruitment
- Japan
Study participating centres
Japan
Japan
Japan
Japan
Japan
Japan
Japan
Japan
Japan
Japan
Sponsor information
Hospital/treatment centre
1 Kawasumi
Mizuho-cho
Mizuho-ku
Nagoya
4678601
Japan
| Phone | +81 52-851-5511 |
|---|---|
| irb_jimu@med.nagoya-cu.ac.jp | |
| Website | https://w3hosp.med.nagoya-cu.ac.jp/english/ |
"ROR" |
https://ror.org/02adg5v98 |
Funders
Funder type
Charity
No information available
No information available
No information available
Results and Publications
| Intention to publish date | 30/09/2029 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be available upon request from Natsuo Tomita (e-mail: c051728@yahoo.co.jp). |
Editorial Notes
23/11/2022: Trial's existence confirmed by IRB of Nagoya City University Graduate School of Medical Sciences.
