Pyrotinib Combined With Brain Radiotherapy in Breast Cancer Patients With Brain Metastases

Sponsor

Fudan University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04582968

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Brain metastases occur in 30-50% of patients with metastatic HER2-positive breast cancer. Pyrotinib is an irreversible pan-ErbB receptor tyrosine kinase inhibitor (TKI) with activity against epidermal growth factor receptor (EGFR)/HER1, HER2, and HER4. This study consists of two parts. In a phase Ib part, investigators will explore the safety and tolerance of Pyrotinib Plus Capecitabine combined with brain radiotherapy. After completing the phase Ib part, investigators will review the data and decide whether this patient is included in before the start of a phase II part. In the phase II part, investigators will evaluate the efficacy of Pyrotinib Plus Capecitabine combined with brain radiotherapy in patients with HER2 positive breast cancer patients with brain metastases.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Brain Metastases HER2-positive Breast Cancer	Other: Pyrotinib Plus Capecitabine combined with brain radiotherapy	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

47 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase Ib/II Pilot Study of Pyrotinib Plus Capecitabine Combined With Brain Radiotherapy in HER2 Positive Breast Cancer Patients With Brain Metastases

Actual Study Start Date :

Sep 1, 2019

Anticipated Primary Completion Date :

Nov 30, 2021

Anticipated Study Completion Date :

Jun 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pyrotinib Plus Capecitabine combined with brain radiotherapy Fractionated stereotactic radiotherapy(FSRT) or whole brain radiation therapy (WBRT) Drug: Pyrotinib combined with capecitabine pyrotinib 400 mg once daily; Capecitabine 1000 mg/m2 per day on day 1 through 14, every 21 days.	Other: Pyrotinib Plus Capecitabine combined with brain radiotherapy Drug combined with radiation

Arm

Intervention/Treatment

Experimental: Pyrotinib Plus Capecitabine combined with brain radiotherapy

Fractionated stereotactic radiotherapy(FSRT) or whole brain radiation therapy (WBRT) Drug: Pyrotinib combined with capecitabine pyrotinib 400 mg once daily; Capecitabine 1000 mg/m2 per day on day 1 through 14, every 21 days.

Other: Pyrotinib Plus Capecitabine combined with brain radiotherapy

Drug combined with radiation

Outcome Measures

Primary Outcome Measures

Assess safety and tolerability of Pyrotinib Plus Capecitabine combined with brain radiotherapy(Phase Ib part) [8 weeks]
AEs will be assessed according to CTCAE version 4.03. (1)Initially 3 patients will be accrued and treated with combined therapy as a lead-in safety phase. Enrollment of the study will not proceed if patients in the safety lead-in phase experience unacceptable toxicities including neurologic, hematologic and other dose limiting toxicities.(see protocol) (b)If one of initially 3 patients has experienced unacceptable toxicities, 3 more patients will be accrued . (3)If two or more patients are unable to complete radiation therapy (RT) due to toxicity related to Pyrotinib Plus Capecitabine combined with brain radiotherapy, accrual will be suspended and the study will be stopped. (4) If 3+3 patients are able to complete the treatment without unacceptable toxicities, 6 more patients will be accrued in Ib part.
Intracranial local tumor control rate （Phase II part) [2 years]
All intracranial progression

Secondary Outcome Measures

Intracranial local tumor control rate with FSRT or WBRT [2 years]
Intracranial local tumor control rate
Intracranial Progression-Free Survival (PFS) [2 years]
Time from the date of radiotherapy to the investigator-determined date of progression (determined by RANO) or death due to any cause, whichever occurs first
Extracranial Progression-Free Survival (PFS) [2 years]
OS (overall survival) [3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Pathologically confirmed HER2 positive advanced breast cancer
Age>18 years. 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)
LVEF ≥ 50%
QTcF < 480 ms
INR≤1.5×ULN，APTT≤1.5×ULN
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 unable to swallow, with chronic diarrhea, intestinal obstruction, or multiple factors that affect drug use and absorption
History of allergy to pyrotinib or capetabine
History of immunodeficiency, including HIV positive, active HBV/HCV or other acquired, congenital immunodeficiency disease, or organ transplantation history
Previous use of pyrotinib combined with capetabine