Pyrotinib in Combination With Capecitabine in Patients With Trastuzumab-resistant HER2-positive Advanced Breast Cancer

• ClinicalTrials.gov Identifier: NCT04001621
• Recruitment Status: Active, not recruiting
• First Posted: June 28, 2019
• Last Update Posted: December 8, 2022
• Sponsor: Fudan University
• Information provided by (Responsible Party): Xichun Hu, Fudan University

Study Description

Brief Summary:

Trastuzumab resistance, which is a common therapeutic challenge in HER2 positive metastatic breast cancer, is not fully understood. Pyrotinib is an oral tyrosine kinase inhibitor targeting EGFR, HER-2 and HER-4 receptors. More general inhibition of ErbB family with pyrotinib could provide additional benefit. This study is designed to evaluate the efficacy and safety of pyrotinib in combination with capecitabine in patients with HER2 positive locally advanced or metastatic breast cancer who had early failure on or after trastuzumab treatment.

Condition or disease	Intervention/treatment	Phase
Metastatic Breast Cancer	Drug: Pyrotinib combined with capecitabine	Phase 2

Detailed Description:

A multi-center, one-arm, open label design study, which is planned to enroll 100 patients with trastuzumab-resistant HER2-positive advanced breast cancer.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Pyrotinib in Combination With Capecitabine in Patients With Trastuzumab-resistant HER2-positive Advanced Breast Cancer
• Actual Study Start Date: June 26, 2019
• Estimated Primary Completion Date: May 31, 2023
• Estimated Study Completion Date: December 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Pyrotinib plus capecitabine; pyrotinib(400 mg once daily) + capecitabine (2000 mg/m^2 daily, 1000 mg/m^2 BID)	Drug: Pyrotinib combined with capecitabine; pyrotinib 400 mg once daily; Capecitabine 1000 mg/m2 per day on day 1 through 14, every 21 days.

Outcome Measures

Primary Outcome Measures :

1. Progression Free Survival (PFS) [ Time Frame: Estimated 12 months ]
   From enrollment to progression or death (for any reason)

Secondary Outcome Measures :

1. Objective Response Rate (ORR) [ Time Frame: Estimated 12 months ]
   Ratio of CR and PR in all subjects
2. Duration of Response (DOR) [ Time Frame: Estimated 12 months ]
   The first evaluation of CR or PR to progression or death (for any reason)
3. Clinical Benefit rate (CBR) [ Time Frame: Estimated 12 months ]
   Ratio of CR,PR and SD greater than or equal to 24 weeks in all subjects
4. Overall Survival (OS) [ Time Frame: Estimated 24 months ]
   From enrollment to death (for any reason)
5. Adverse Events and Serious Adverse Events [ Time Frame: From informed consent through 28 days following treatment completion ]
   Safety

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Pathologically confirmed HER2 positive patients with locally advanced or metastatic breast cancer: HER2 IHC 3+, or HER2 IHC 2+ and FISH detection gene amplification
2. Aged ≥18 and ≤70 years.
3. ECOG performance status of 0 to 1.
4. Life expectancy of more than 12 weeks;
5. At least one measurable lesion exists(RECIST 1.1)

6. Patients with trastuzumab resistance is defined as follows:

   Progression during or within 12 months after treatment in neoadjuvant or adjuvant setting (at least 9 weeks of trastuzumab treatment); Or Progression during or within 6 months after treatment for locally advanced or metastatic disease in the first-line setting (at least 6 weeks of trastuzumab treatment).

7. At least 4 weeks from the last treatment of trastuzumab or chemotherapy，at least 5 times of t1/2 or 4 weeks from the last treatment of endocrine therapy（the shorter one is preferred）
8. Known hormone receptor status
9. For patients with brain metastases, local treatment (including whole cranial radiotherapy, SBRT, etc.) is required and the brain lesions are stable for ≥ 3 months without the need for dexamethasone or mannitol treatment

10. Patients with adequate organ function before enrollment:

    1. ANC≥1.5×10^9/L
    2. PLT≥100×10^9/L
    3. Hb≥90 g/L
    4. TBIL≤1.5×ULN
    5. ALT and AST≤3×ULN, （ALT and AST≤5×ULN in patients with liver metastases）
    6. Cr≤1.5×ULN and the creatinine clearance rate≥50 mL/min
    7. LVEF ≥ 50%
    8. QTcF < 480 ms
11. Signed informed consent.

Exclusion Criteria:

1. Patients with meningeal metastasis and / or spinal cord metastasis;
2. Patients unable to swallow, with chronic diarrhea, intestinal obstruction, or multiple factors that affect drug use and absorption;
3. Patients with malignant serious effusion which cannot be controlled by drainage or other methods;
4. Less than 4 weeks from the last treatment in last clinical trial;
5. Known dihydropyrimidine dehydrogenase (DPD) deficiency;
6. Receiving any other antitumor therapy;
7. History of other malignancy within the last 5 years, except for carcinoma in situ of cervix, basal cell carcinoma or squamous cell carcinoma of the skin that has been previously treated with curative intent;
8. Received radiotherapy, surgery (excluding local puncture) within 4 weeks prior to enrollment; received anti-tumor endocrine therapy after entering the screening period;
9. Previous or ongoing use of HER2-targeted tyrosine kinase inhibitors (lapatinib, neratinib or pyrotinib);
10. Previous use of capecitabine or capecitabine not tolerated, except that capecitabine efficacy cannot be judged or capecitabine discontinuation for 3 months or more;
11. Patients with serious heart disease;
12. Allergy to pyrotinib; history of immunodeficiency, including HIV positive, active HBV/HCV or other acquired, congenital immunodeficiency disease, or organ transplantation history;
13. Known history of neurological or psychiatric disease, including epilepsy or dementia;
14. Patients during pregnancy or lactation, patients with childbearing potential tested positive in baseline pregnancy test, or patients unwilling to take effective contraceptive measures throughout the trial;
15. Evidence of significant medical illness that will substantially increase the risk on the participation or completion of the study in the investigator's judgment. Examples included, but not limited to, hypertension, severe diabetes, etc;
16. Patients not eligible for this study judged by the investigator.

Contacts and Locations

Locations

China

Fudan University Shanghai Cancer Center

Shanghai, China, 200032

Sponsors and Collaborators

Fudan University

Investigators

• Principal Investigator: Xichun Hu; Department of Oncology

More Information

• Responsible Party: Xichun Hu, professor, Fudan University
• ClinicalTrials.gov Identifier: NCT04001621
• Other Study ID Numbers: HR-BLTN-003
• First Posted: June 28, 2019
• Last Update Posted: December 8, 2022
• Last Verified: December 2022

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

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Capecitabine; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents