Pyrotinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in Patients With HER2+ Metastatic Breast Cancer. (PHOEBE)

NCT03080805 | Unknown Phase 3 FDA Drug

• 1 other identifier: HR-BLTN-Ⅲ-MBC
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

Pyrotinib is an oral tyrosine kinase inhibitor targeting both HER-1 and HER-2 receptors. This study is a randomized,open-label,multi-center,active-controlled, parallel design study of the combination of pyrotinib and capecitabine versus Lapatinib plus capecitabine in HER2+ MBC patients, who have prior received taxane and trastuzumab.Patients will be randomized in a 1:1 ratio to one of the following treatment arms.Arm A: pyrotinib (400 mg once daily) + capecitabine (1000 mg/m\^2 twice daily),Arm B: Lapatinib (1250 mg once daily) + capecitabine (1000 mg/m\^2 twice daily).Patients will receive either arm of therapy until disease progression, unacceptable toxicity, or withdrawalof consent.

Conditions

HER2 Positive Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival(PFS)

  From infromed consent to progression or death

  Estimated 10 months

Secondary Outcomes (6)

• Safety: AE

  AE recorded from infromed consent to 28 days after treatment completion

• Overall Survival (OS)

  Estimated 30 months

• Objective Response Rate (ORR)

  Estimated 10 months

• Time to Progression (TTP)

  Estimated 10 months

• Duration of Response (DOR)

  Estimated 10 months

Study Arms (2)

Pyrotinib Plus Capecitabine

EXPERIMENTAL

Drug: Pyrotinib Plus Capecitabine

Lapatinib Plus Capecitabine

ACTIVE COMPARATOR

Drug: Lapatinib Plus Capecitabine

Interventions

Pyrotinib Plus Capecitabine DRUG

pyrotinib(400 mg once daily) + capecitabine (2000 mg/m\^2 daily, 1000 mg/ m\^2 BID)

Pyrotinib Plus Capecitabine

Lapatinib Plus Capecitabine DRUG

Lapatinib (1250 mg once daily)+ capecitabine (2000 mg/m\^2 daily, 1000 mg/m\^2 BID)

Lapatinib Plus Capecitabine

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged ≥18 and ≤70 years.
• ECOG performance status of 0 to 1.
• Life expectancy of more than 12 weeks.
• According to RECIST 1.1, at least one measurable lesion exists
• Histologically or cytologic confirmed HER2 positive metastatic breast cancer.
• Prior treatment with trastuzumab (≥2 cycles in metastatic setting, or
• ≥3 months in adjuvant/neoadjuvant setting) and Taxane(≥2 cycles in any setting or untill unendurable AE or progression during treatment).
• Previously reveived ≤2 chemotherapy regimens in metastasis setting;
• Required laboratory values including following parameters:
• ANC: ≥ 1.5 x 10\^9/L; Platelet count: ≥ 90 x 10\^9/L; Hemoglobin: ≥ 90 g/L; Total bilirubin: ≤ 1.5 x upper limit of normal (ULN); ALT and AST: ≤ 2 x ULN(patients with liver metastases: ≤5 x ULN); BUN and Creatinine:
• ≤ 1x ULN;CCR≥50 mL/min;LVEF: ≥ 50%;QTcF: \< 450 ms (male)，\< 470 ms（female）;
• Signed informed consent.

You may not qualify if:

• Received capecitabine in metastatic setting;
• Received HER2 targeted tyrosine kinase inhibitor (including Lapatinib, Neratinib and Pyrotinib);
• Cumulated dosage of Doxorubincin \>400 mg/m\^2 or Epirubicin \>800 mg/m\^2 or equal dosage of other anthracycline drugs in adjuvant/neoadjuvant/metastatic setting );
• Received surgery，chemotherapy,radiotherapy or target therapy within 28 days prior to randomization. Received hormone therapy within 7 days prior to randomization;
• Participated in other clinical trial within 28 days prior to randomization.
• Known dihydro pyrimidine dehydrogenase（DPD）defect;
• CT or MRI confirmed brain metastases;
• Bone or skin lesion as unique target lesion;
• Second malignancies within 5 years, except for cured skin basal cell carcinoma,carcinoma in-situ of uterine cervix and squamous-cell carcinoma;
• Factors influencing the usage of oral administration (e.g. unable to swallow, chronic diarrhea and intestinal obstruction, etc.);
• Uncontrolled third space effusion (such as pleural fluid and ascites) by drainage or other clinical intervention;
• Receiving any other anti-tumour therapy after informed consent;
• Unprogressed after or during the last anti-tumour therapy,according to RECIST1.1;
• History of any kind of Heart disease,including 1)Angina pectoris; (2) Arrhythmia required medication or with clinical significance; (3) Myocardial infarction; (4) Heart failure; (5) Any other heart disease judged by researcher as not suitable for participating in this study, etc;
• History of Immunodeficiency, acquired or congenital immunodeficiency (HIV positive) ,history of organ transplantation;

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead

Study Sites (1)

Cancer Institute and Hospital,Chinese Academy of Medical Science

Beijing, Beijing Municipality, China

Location

Related Publications (2)

• Bao Y, Zhang Z, He X, Cai L, Wang X, Li X. Cost-Effectiveness of Pyrotinib Plus Capecitabine versus Lapatinib Plus Capecitabine for the Treatment of HER2-Positive Metastatic Breast Cancer in China: A Scenario Analysis of Health Insurance Coverage. Curr Oncol. 2022 Aug 23;29(9):6053-6067. doi: 10.3390/curroncol29090476.

  PMID: 36135045 DERIVED

• Xu B, Yan M, Ma F, Hu X, Feng J, Ouyang Q, Tong Z, Li H, Zhang Q, Sun T, Wang X, Yin Y, Cheng Y, Li W, Gu Y, Chen Q, Liu J, Cheng J, Geng C, Qin S, Wang S, Lu J, Shen K, Liu Q, Wang X, Wang H, Luo T, Yang J, Wu Y, Yu Z, Zhu X, Chen C, Zou J; PHOEBE Investigators. Pyrotinib plus capecitabine versus lapatinib plus capecitabine for the treatment of HER2-positive metastatic breast cancer (PHOEBE): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2021 Mar;22(3):351-360. doi: 10.1016/S1470-2045(20)30702-6. Epub 2021 Feb 11.

  PMID: 33581774 DERIVED

MeSH Terms

Interventions

pyrotinib; Capecitabine; Lapatinib

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2017
• First Posted: March 15, 2017
• Study Start: May 3, 2017
• Primary Completion: March 31, 2019
• Study Completion: March 1, 2021
• Last Updated: June 18, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)