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

• ClinicalTrials.gov Identifier: NCT03080805
• Recruitment Status: Unknown
• First Posted: March 15, 2017
• Last Update Posted: June 18, 2020
• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Information provided by (Responsible Party): Jiangsu HengRui Medicine Co., Ltd.

Tracking Information

• First Submitted Date: March 3, 2017
• First Posted Date: March 15, 2017
• Last Update Posted Date: June 18, 2020
• Actual Study Start Date: May 3, 2017
• Actual Primary Completion Date: March 31, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 14, 2017)

Progression Free Survival(PFS) [ Time Frame: Estimated 10 months ]

From infromed consent to progression or death

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 14, 2017)

• Safety: AE [ Time Frame: AE recorded from infromed consent to 28 days after treatment completion ]
  AE
• Overall Survival (OS) [ Time Frame: Estimated 30 months ]
  From infromed consent to death
• Objective Response Rate (ORR) [ Time Frame: Estimated 10 months ]
  CR+PR
• Time to Progression (TTP) [ Time Frame: Estimated 10 months ]
  From infromed consent to progression
• Duration of Response (DOR) [ Time Frame: Estimated 10 months ]
  CR+PR+SD
• Clinical Benefit rate (CBR) [ Time Frame: Estimated 10 months ]
  CR+PR+SD≥24 weeks

• 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 Plus Capecitabine Versus Lapatinib Plus Capecitabine in Patients With HER2+ Metastatic Breast Cancer. (PHOEBE)
• Official Title: A Randomised, Open-label, Parallel Controlled, Multicentre, Phase 3 Clinical Trial of Pyrotinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in Patients With HER2+ Metastatic Breast Cancer:
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: HER2 Positive Metastatic Breast Cancer

Intervention

• Drug: Pyrotinib Plus Capecitabine
  pyrotinib(400 mg once daily) + capecitabine (2000 mg/m^2 daily, 1000 mg/ m^2 BID)
• Drug: Lapatinib Plus Capecitabine
  Lapatinib (1250 mg once daily)+ capecitabine (2000 mg/m^2 daily, 1000 mg/m^2 BID)

Study Arms

• Experimental: Pyrotinib Plus Capecitabine
  Intervention: Drug: Pyrotinib Plus Capecitabine
• Active Comparator: Lapatinib Plus Capecitabine
  Intervention: Drug: Lapatinib Plus Capecitabine

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: March 14, 2017): 240
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 2021
• Actual Primary Completion Date: March 31, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Aged ≥18 and ≤70 years.
2. ECOG performance status of 0 to 1.
3. Life expectancy of more than 12 weeks.
4. According to RECIST 1.1, at least one measurable lesion exists
5. Histologically or cytologic confirmed HER2 positive metastatic breast cancer.

6. 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).

7. Previously reveived ≤2 chemotherapy regimens in metastasis setting;

8. 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）;

9. Signed informed consent.

Exclusion Criteria:

1. Received capecitabine in metastatic setting;
2. Received HER2 targeted tyrosine kinase inhibitor (including Lapatinib, Neratinib and Pyrotinib);
3. 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 );
4. Received surgery，chemotherapy,radiotherapy or target therapy within 28 days prior to randomization. Received hormone therapy within 7 days prior to randomization;
5. Participated in other clinical trial within 28 days prior to randomization.
6. Known dihydro pyrimidine dehydrogenase（DPD）defect;
7. CT or MRI confirmed brain metastases;
8. Bone or skin lesion as unique target lesion;
9. Second malignancies within 5 years, except for cured skin basal cell carcinoma,carcinoma in-situ of uterine cervix and squamous-cell carcinoma;
10. Factors influencing the usage of oral administration (e.g. unable to swallow, chronic diarrhea and intestinal obstruction, etc.);
11. Uncontrolled third space effusion (such as pleural fluid and ascites) by drainage or other clinical intervention;
12. Receiving any other anti-tumour therapy after informed consent;
13. Unprogressed after or during the last anti-tumour therapy,according to RECIST1.1;
14. 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;
15. History of Immunodeficiency, acquired or congenital immunodeficiency (HIV positive) ,history of organ transplantation;
16. History of neurological or psychiatric disorders, including epilepsy or dementia;
17. Concomitant disease judged by investigators that may bring serious harm to the safety of patients or the completion of this study;
18. All female patients in breastfeeding period or in child-bearing period or with positive pregnancy test result or refusing to take a reliable method of birth control during the study;
19. Any other situations judged by investigator as not suitable for participating in this study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (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: NCT03080805
• Other Study ID Numbers: HR-BLTN-Ⅲ-MBC
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Jiangsu HengRui Medicine Co., Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Jiangsu HengRui Medicine Co., Ltd.
• Verification Date: June 2020