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

• ClinicalTrials.gov Identifier: NCT04582968
• Recruitment Status: Active, not recruiting
• First Posted: October 12, 2020
• Last Update Posted: January 18, 2023
• Sponsor: Fudan University
• Information provided by (Responsible Party): Xiaoli Yu, Fudan University

Tracking Information

• First Submitted Date: October 7, 2020
• First Posted Date: October 12, 2020
• Last Update Posted Date: January 18, 2023
• Actual Study Start Date: January 2, 2020
• Actual Primary Completion Date: August 12, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 9, 2020)

• Assess safety and tolerability of Pyrotinib Plus Capecitabine combined with brain radiotherapy(Phase Ib part) [ Time Frame: 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) [ Time Frame: 2 years ]
  All intracranial progression

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 9, 2020)

• Intracranial local tumor control rate with FSRT or WBRT [ Time Frame: 2 years ]
  Intracranial local tumor control rate
• Intracranial Progression-Free Survival (PFS) [ Time Frame: 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) [ Time Frame: 2 years ]
• OS (overall survival) [ Time Frame: 3 years ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Breast Cancer
• Brain Metastases
• HER2-positive Breast Cancer

Intervention

Other: Pyrotinib Plus Capecitabine combined with brain radiotherapy

Drug combined with radiation

Study Arms

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.

Intervention: Other: Pyrotinib Plus Capecitabine combined with brain radiotherapy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: January 14, 2023): 39
• Original Estimated Enrollment (submitted: October 9, 2020): 47
• Estimated Study Completion Date: August 12, 2023
• Actual Primary Completion Date: August 12, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT04582968
• Other Study ID Numbers: FDRT-BC010
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Xiaoli Yu, Fudan University
• Original Responsible Party: Same as current
• Current Study Sponsor: Fudan University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Xiaoli Yu, MD PhD; Fudan University

• PRS Account: Fudan University
• Verification Date: January 2023