FSRT in Breast Cancer Patients With Brain Metastases

A Phase II Pilot Study of Fractionated Stereotactic Radiotherapy(FSRT) in Breast Cancer Patients With 1 to 10 Brain Metastases

Brain metastasis accounted for 10-15% of all breast cancer patients and even higher in patients with triple negative and HER2 overexpressed subtype. Stereotactic radiation is the standard option for patients with 1-4 brain metastases. Among patients with 1-4 brain metastases, many studies suggest that stereotactic radiation results in fewer neurologic side effects than whole brain radiation. Also, several studies had demonstrated that 5-10 lesions had similar overall survival by using whole brain radiotherapy or stereotactic radiotherapy. Fractionated stereotactic radiotherapy(FSRT) is increasingly administered in the brain metastatic patients and retrospective studies had shown that FSRT had better local control and lower brain radiation necrosis than single fraction stereotactic radiation. Therefore, In this study, we explore to treat 1-10 brain metastasis lesion in breast cancer patients with FSRT.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer; Brain Metastases
• Intervention / Treatment: Radiation: Fractionated stereotactic radiotherapy(FSRT)

Detailed Description

Breast cancer patients with 1-10 brain metastasis will be treated with FSRT for brain metastasis. 3 to 5 fractions and 8Gy per fraction will be used for these patients based on the lesion number and volume.

• Study Type: Interventional
• Enrollment (Anticipated): 170
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jin Meng; Phone Number: +86 18121299532; Email: jademj@126.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Fudan University Shanghai Cancer Center
    • Contact: Zhaozhi yang, PhD; Phone Number: +8618017317126; Email: yzzhi2014@163.com
    • Contact: Jin Meng; Phone Number: +8618121299532; Email: jademj@126.com
    • Principal Investigator: Zhaozhi Yang, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Histologically confirmed HER2 positive advanced breast cancer
• Age>18 years.
• 1 to 10 brain metastases confirmed by enhanced brain MRI
• KPS≥70
• Life expectancy of more than 12 weeks
• Prior therapy of oral dexamethasone not exceeding 16mg/d
• Time interval from prior therapy was more than 2 weeks, and evaluation of adverse events is no more than grade 1.
• Maximum diameter of intracranial metastases is less than 3cm measured by enhanced brain MRI(2-3mm)
• Prior endocrine therapy were allowed
• Anti-Her2 targeted treatment were allowed
• Screening laboratory values must meet the following criteria( and should be obtained within 28 days prior to registration):

Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L, Platelets≥ 90 x 109/L, Hemoglobin ≥ 90 g/L Aspartate aminotransferase/alanine aminotransferase (AST/ALT) ≤2.5 x ULN without liver metastasis,≤ 5 x ULN with liver metastases Serum BUN and creatinine ≤ 1.5 x Upper Limit of Normal (ULN)

• Time interval from chemotherapy was more than 2 weeks, endocrine therapy and anti-Her2 targeted treatment are allowed to be used concurrently with FSRT
• Signed the informed consent form prior to patient entry

Exclusion Criteria:

• Leptomeningeal or hemorrhagic metastases
• Uncontrolled epilepsy
• Severe complication: cardiovascular disease, end-stage renal disease, severe hepatic disease, infection etc.
• Pregnancy or lactation period， women of child-bearing age who are unwilling to accept contraceptive measures.
• Inability to complete enhanced MRI
• Patients who are difficult or unable to be followed-up
• Not suitable for inclusion for specific reasons judged by sponsor
• Patients who are receiving cytotoxic drug concomitantly
• Have received prior radiotherapy for brain metastasis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FSRT; 3 to 5 fractions and 8Gy per fraction will be used for breast cancer patients with 1-10 brain metastases based on the lesion number and volume.	Radiation: Fractionated stereotactic radiotherapy(FSRT); 3 to 5 fractions and 8Gy per fraction will be used for breast cancer patients with 1-10 brain metastases based on the lesion number and volume.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
intracranial local tumor control rate	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intracranial distant metastasis rate	intracranial distant metastasis after FSRT will be determined by the development of intracranial distant metastasis is determined by new lesions outside of the irradiated area.	2 years
Intracranial Progression-Free Survival (PFS)	Time from the date of radiotherapy to the investigator-determined date of progression or death due to any cause, whichever occurs first	2 years
overall survival(OS)	time from the date of informed consent until to the date of death, regardless of the cause of death.	3 years
Adverse events	AEs were graded according to the National Cancer Institute's Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0.3	2 years

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2019
• Primary Completion (Anticipated): July 1, 2021
• Study Completion (Anticipated): July 1, 2022

Study Registration Dates

• First Submitted: August 16, 2019
• First Submitted That Met QC Criteria: August 16, 2019
• First Posted (Actual): August 19, 2019

Study Record Updates

• Last Update Posted (Actual): August 19, 2019
• Last Update Submitted That Met QC Criteria: August 16, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Breast Neoplasms; Neoplasm Metastasis; Brain Neoplasms
• Other Study ID Numbers: FDRT-BC009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No