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

NCT04582968 | Unknown Phase 1 DMC

• 1 other identifier: FDRT-BC010
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer; Brain Metastases; HER2-positive Breast Cancer

Keywords

pyrotinib; brain radiotherapy

Outcome Measures

Primary Outcomes (2)

• Assess safety and tolerability of Pyrotinib Plus Capecitabine combined with brain radiotherapy(Phase Ib part)

  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.

  8 weeks

• Intracranial local tumor control rate （Phase II part)

  All intracranial progression

  2 years

Secondary Outcomes (4)

• Intracranial local tumor control rate with FSRT or WBRT

  2 years

• Intracranial Progression-Free Survival (PFS)

  2 years

• Extracranial Progression-Free Survival (PFS)

  2 years

• OS (overall survival)

  3 years

Study Arms (1)

Pyrotinib Plus Capecitabine combined with brain radiotherapy

EXPERIMENTAL

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

Interventions

Pyrotinib Plus Capecitabine combined with brain radiotherapy OTHER

Drug combined with radiation

Pyrotinib Plus Capecitabine combined with brain radiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, 200032, China

Location

Related Publications (2)

• Dai L, Gao T, Guo R, Chen Y, Wang J, Zhou S, Tang Y, Chen D, Huang S. Efficacy and safety of pyrotinib-based regimens in HER2 positive metastatic breast cancer: A retrospective real-world data study. Neoplasia. 2024 Oct;56:101029. doi: 10.1016/j.neo.2024.101029. Epub 2024 Jul 17.

  PMID: 39024777 DERIVED

• Yang Z, Meng J, Mei X, Mo M, Xiao Q, Han X, Zhang L, Shi W, Chen X, Ma J, Palmer J, Shao Z, Zhang Z, Yu X, Guo X. Brain Radiotherapy With Pyrotinib and Capecitabine in Patients With ERBB2-Positive Advanced Breast Cancer and Brain Metastases: A Nonrandomized Phase 2 Trial. JAMA Oncol. 2024 Mar 1;10(3):335-341. doi: 10.1001/jamaoncol.2023.5791.

  PMID: 38175627 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Brain Neoplasms

Interventions

pyrotinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Xiaoli Yu, MD PhD

  Fudan University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 7, 2020
• First Posted: October 12, 2020
• Study Start: January 2, 2020
• Primary Completion: August 12, 2022
• Study Completion: August 12, 2023
• Last Updated: January 18, 2023

Record last verified: 2023-01

Locations

CN (1)