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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer; HER2-positive Breast Cancer; Brain Metastases
• Intervention / Treatment: Other: Pyrotinib Plus Capecitabine combined with brain radiotherapy

• Study Type: Interventional
• Enrollment (Anticipated): 39
• Phase: Phase 2; Phase 1

Contacts and Locations

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

Study Locations

• China
  • Shanghai, China, 200032
    • Fudan University Shanghai Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Pathologically confirmed HER2 positive advanced breast cancer
2. Age>18 years. brain metastases confirmed by enhanced brain MRI
3. KPS≥70
4. Life expectancy of more than 12 weeks
5. Prior therapy of oral dexamethasone not exceeding 16mg/d
6. Time interval from prior therapy was more than 2 weeks, and evaluation of adverse events is no more than grade 1.
7. Maximum diameter of intracranial metastases is less than 3cm measured by enhanced brain MRI(2-3mm)
8. Prior endocrine therapy were allowed
9. Anti-Her2 targeted treatment were allowed

10. Screening laboratory values must meet the following criteria( and should be obtained within 28 days prior to registration):

    1. Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L, Platelets≥ 90 x 109/L, Hemoglobin ≥ 90 g/L
    2. Aspartate aminotransferase/alanine aminotransferase (AST/ALT) ≤2.5 x ULN without liver metastasis,≤ 5 x ULN with liver metastases
    3. Serum BUN and creatinine ≤ 1.5 x Upper Limit of Normal (ULN)
    4. LVEF ≥ 50%
    5. QTcF < 480 ms
    6. INR≤1.5×ULN，APTT≤1.5×ULN
11. Signed the informed consent form prior to patient entry

Exclusion Criteria:

1. Leptomeningeal or hemorrhagic metastases
2. uncontrolled epilepsy
3. Severe complication: cardiovascular disease, end-stage renal disease, severe hepatic disease, infection etc.
4. Pregnancy or lactation period， women of child-bearing age who are unwilling to accept contraceptive measures.
5. Inability to complete enhanced MRI
6. Patients who are difficult or unable to be followed-up
7. Not suitable for inclusion for specific reasons judged by sponsor
8. Patients unable to swallow, with chronic diarrhea, intestinal obstruction, or multiple factors that affect drug use and absorption
9. History of allergy to pyrotinib or capetabine
10. History of immunodeficiency, including HIV positive, active HBV/HCV or other acquired, congenital immunodeficiency disease, or organ transplantation history
11. Previous use of pyrotinib combined with capetabine

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: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intracranial local tumor control rate with FSRT or WBRT	Intracranial local tumor control rate	2 years
Intracranial Progression-Free Survival (PFS)	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	2 years
Extracranial Progression-Free Survival (PFS)		2 years
OS (overall survival)		3 years

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Xiaoli Yu, MD PhD, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2020
• Primary Completion (Actual): August 12, 2022
• Study Completion (Anticipated): August 12, 2023

Study Registration Dates

• First Submitted: October 7, 2020
• First Submitted That Met QC Criteria: October 9, 2020
• First Posted (Actual): October 12, 2020

Study Record Updates

• Last Update Posted (Actual): January 18, 2023
• Last Update Submitted That Met QC Criteria: January 14, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: pyrotinib; brain radiotherapy
• 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; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine
• Other Study ID Numbers: FDRT-BC010

Drug and device information, study documents

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