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

Primary Purpose

Breast Cancer, Brain Metastases, HER2-positive Breast Cancer

Status

Active

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

Pyrotinib Plus Capecitabine combined with brain radiotherapy

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring pyrotinib, brain radiotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept 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):
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
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

Sites / Locations

Fudan University Shanghai Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pyrotinib Plus Capecitabine combined with brain radiotherapy

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Intracranial local tumor control rate （Phase II part)

All intracranial progression

Secondary Outcome Measures

Intracranial local tumor control rate with FSRT or WBRT

Intracranial local tumor control rate

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

Extracranial Progression-Free Survival (PFS)

OS (overall survival)

Full Information

NCT ID

NCT04582968

First Posted

October 7, 2020

Last Updated

January 14, 2023

Sponsor

Fudan University

1. Study Identification

Unique Protocol Identification Number

NCT04582968

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

January 2, 2020 (Actual)

Primary Completion Date

August 12, 2022 (Actual)

Study Completion Date

August 12, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Fudan University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer, Brain Metastases, HER2-positive Breast Cancer

Keywords

pyrotinib, brain radiotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

39 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Pyrotinib Plus Capecitabine combined with brain radiotherapy

Arm Type

Experimental

Arm Description

Intervention Type

Other

Intervention Name(s)

Pyrotinib Plus Capecitabine combined with brain radiotherapy

Intervention Description

Drug combined with radiation

Primary Outcome Measure Information:

Title

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

Description

Time Frame

8 weeks

Title

Intracranial local tumor control rate （Phase II part)

Description

All intracranial progression

Time Frame

2 years

Secondary Outcome Measure Information:

Title

Intracranial local tumor control rate with FSRT or WBRT

Description

Intracranial local tumor control rate

Time Frame

2 years

Title

Intracranial Progression-Free Survival (PFS)

Description

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

Time Frame

2 years

Title

Extracranial Progression-Free Survival (PFS)

Time Frame

2 years

Title

OS (overall survival)

Time Frame

3 years

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Xiaoli Yu, MD PhD

Organizational Affiliation

Fudan University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Fudan University Shanghai Cancer Center

City

Shanghai

ZIP/Postal Code

200032

Country

China

12. IPD Sharing Statement

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

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