Clinical Trials Logo

Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT04452084
Other study ID # HA-SIB-WBRT
Secondary ID
Status Active, not recruiting
Phase Phase 2
First received
Last updated
Start date June 15, 2020
Est. completion date June 14, 2025

Study information

Verified date March 2024
Source National Cancer Centre, Singapore
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Recently, the evidence supports hippocampal avoidance with whole brain radiotherapy (HA-WBRT) as the recommended treatment option in patients with good prognosis and multiple brain metastases as it gives better neurocognitive preservation compared to historical whole brain radiotherapy controls. There is however often poor tumour control with this technique due to the low doses given. Stereotactic Radiosurgery (SRS), a form of focused radiotherapy which is given to patients who have a limited number of brain metastases, gives a higher radiation dose to the metastases resulting in better target lesion control. With improvements in radiation technology, advanced dose-painting techniques now allow a simultaneous integrate boost (SIB) dose to lesions whilst minimising doses to the hippocampus to potentially improve brain tumour control and preserve cognitive outcomes (HA-SIB-WBRT). The Investigators believe that the SIB in HA-SIB-WBRT (experimental) will result in better functional and survival outcomes compared to HA-WBRT (control). Patients who are fit, have multiple brain metastases (5-25 lesions) and reasonable life expectancy (>6 months) will be recruited from NCCS over 2 years. Patients will be followed up the over the following year with imaging, toxicity data, quality of life, activities of daily living and cognitive measurements at set time points. The results will be compared across the 2 arms. Patients with brain metastases are living longer. Maintaining functional independence and brain metastases control is thus increasingly important. Improved radiotherapy treatment techniques could provide better control and survival outcomes whilst maintain QoL and functional capacity.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 42
Est. completion date June 14, 2025
Est. primary completion date June 14, 2024
Accepts healthy volunteers No
Gender All
Age group 21 Years to 80 Years
Eligibility Inclusion Criteria: - 21-80 years old patients with radiological confirmed brain metastases (5-25 lesions) - Histologically proven malignancy of primary cancer - ECOG performance status = 2 - Maximum lesion or cavity size = 5cm - For patients with large (= 3cm) lesions, a neurosurgical consult is recommended as the risk of cerebral oedema and hydrocephalus is higher with RT. A Ventricular-peritoneal shunt/ surgical excision may be required prior to planning of RT - If brain surgery or other invasive procedures are performed, the treatment can only begin at least 2-weeks post-procedure - Life expectancy of at least 6 months - Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential - Women of childbearing potential and male participants who are sexually active must agree to use a medically effective means of birth control throughout protocol treatment - Not recommended or does not want Stereotactic Radiosurgery (SRS) - Agrees to be randomised to either HA-WBRT or HA-SIB-WBRT Exclusion Criteria: - Prior whole brain radiotherapy o Prior SRS is not an exclusion. Details of treatment must be recorded. - Concurrent systemic cytotoxic treatment. o If patient is on systemic treatment a treatment break of at least 7 days for immunotherapy or chemotherapy and 3 days for targeted therapy is required before and after radiotherapy. - Leptomeningeal disease - Extensive extracranial disease, not controlled by systemic treatment - Severe, active co-morbidity, defined as follows: - Major medical or psychiatric illness, which in the investigator's opinion would interfere with the completion of therapy and follow up or with full understanding of the risks and potential complications of the therapy; - Unstable angina and/or uncontrolled congestive heart failure; - Myocardial infarction within the last 6 months; - Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; note that patients switched from IV antibiotics and currently on oral antibiotics whose infection is assessed to be adequately treated or controlled are eligible. - Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days prior to registration; - Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. - Dementia, ongoing psychotic episodes or moderate-severe depression (PHQ-9). - Recent stroke in the past 3 months - Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; - ECOG performance status >2 despite a duration of high dose steroids - Symptomatic brain metastases limiting ADLs - Rapid brain progression - Patients unable to give informed consent - Total tumour planning target volume (PTV) >60cc - Radiological evidence of hydrocephalus - Contraindication to Gadolinium contrast-enhanced MRI brain - Patients who are unable to meet expected follow-up schedule (e.g. non-resident patients) - Patients with diagnoses of small cell carcinoma, lymphoma or primary brain tumour

Study Design


Related Conditions & MeSH terms


Intervention

Radiation:
HA-WBRT
The accepted standard HA-WBRT doses in the control arm are 30Gy in 10 fractions.
HA-SIB-WBRT
The doses selected for experimental HA-SIB-WBRT arm are 30Gy in 10 fractions to the whole brain with 40 to 45Gy in 10 fraction SIB doses to tumours.

Locations

Country Name City State
Singapore National Cancer Center Singapore Singapore

Sponsors (3)

Lead Sponsor Collaborator
National Cancer Centre, Singapore Singapore General Hospital, Singhealth Duke-NUS Oncology Academic Clinical Programme (ONCO ACP)

Country where clinical trial is conducted

Singapore, 

Outcome

Type Measure Description Time frame Safety issue
Primary Target lesion progression From time of randomisation to target lesion progression, up to 6 months after last day of radiotherapy.
Secondary Time to symptomatic brain metastases From time of randomisation to symptomatic brain progression, up to 12 months after last day of radiotherapy.
Secondary Incidences of treatment-emergent adverse events (AE) Identified and graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 criteria. From time of randomisation to 12 months after last day of radiotherapy.
Secondary Overall Survival From time of randomisation to death from any cause, up to 12 months after last day of radiotherapy.
Secondary Progression Free Survival From time of randomisation to overall progression, up to 12 months after last day of radiotherapy.
Secondary Cognitive function Assessed using Hopkins Verbal Learning Test From time of randomisation to 12 months after last day of radiotherapy.
See also
  Status Clinical Trial Phase
Active, not recruiting NCT04074096 - Binimetinib Encorafenib Pembrolizumab +/- Stereotactic Radiosurgery in BRAFV600 Melanoma With Brain Metastasis Phase 2
Recruiting NCT04474925 - Pre- Versus Post-operative SRS for Resectable Brain Metastases Phase 3
Recruiting NCT05358340 - Dual Perfusion Imaging for Characterizing Vascular Architecture of Brain Lesions N/A
Recruiting NCT05559853 - Developing a New MRI Technique to Understand Changes in Brain Tumors After Treatment
Completed NCT03189381 - Pilot Phase 2 Study Whole Brain Radiation Therapy With Simultaneous Integrated Boost for Patients With Brain Metastases N/A
Completed NCT02082587 - Toronto BNB Pilot Study N/A
Terminated NCT01551680 - A Trial Evaluating Concurrent Whole Brain Radiotherapy and Iniparib in Multiple Non Operable Brain Metastases Phase 1
Terminated NCT00717275 - Study of Temozolomide to Treat Newly Diagnosed Brain Metastases Phase 2
Recruiting NCT05048212 - A Phase II Study of Nivolumab With Ipilimumab and Cabozantinib in Patients With Untreated Renal Cell Carcinoma Brain Metastases Phase 2
Recruiting NCT03714243 - Blood Brain Barrier Disruption (BBBD) Using MRgFUS in the Treatment of Her2-positive Breast Cancer Brain Metastases N/A
Recruiting NCT05573815 - Evaluation of Clinical Decision Support System for Brain Metastasis Using Brain MR Images N/A
Recruiting NCT04899908 - Stereotactic Brain-directed Radiation With or Without Aguix Gadolinium-Based Nanoparticles in Brain Metastases Phase 2
Completed NCT04507217 - Tislelizumab Combined With Pemetrexed/ Carboplatin in Patients With Brain Metastases of Non-squamous NSCLC Phase 2
Recruiting NCT05452005 - Fluorine-18-AlphaVBeta6-Binding Peptide Positron Emission Tomography in Metastatic Non-Small Cell Lung Cancer Phase 1
Recruiting NCT06457906 - SRS/SRT/Hypo-RT Versus HA-WBRT for No More Than 10 Brain Metastases in SCLC Phase 3
Completed NCT04170777 - Perfexion Registration Using CBCT
Recruiting NCT03027544 - Tomotherapy for Refractory Brain Metastases N/A
Completed NCT04178330 - Tomotherapy as Primary Radiotherapy for Multipule Brain Metastases N/A
Terminated NCT02187822 - Fractionated Stereotactic Radiotherapy (FSRT) in Treatment of Brain Metastases Phase 1
Terminated NCT00538343 - RTA 744 in Breast Cancer Patients With Progression of Previously Irradiated Brain Metastases Phase 2