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

NCT04001621 | Unknown Phase 2 DMC

• 1 other identifier: HR-BLTN-003
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  From enrollment to progression or death (for any reason)

  Estimated 12 months

Secondary Outcomes (5)

• Objective Response Rate (ORR)

  Estimated 12 months

• Duration of Response (DOR)

  Estimated 12 months

• Clinical Benefit rate (CBR)

  Estimated 12 months

• Overall Survival (OS)

  Estimated 24 months

• Adverse Events and Serious Adverse Events

  From informed consent through 28 days following treatment completion

Study Arms (1)

Pyrotinib plus capecitabine

EXPERIMENTAL

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

Drug: Pyrotinib combined with capecitabine

Interventions

Pyrotinib combined with capecitabine DRUG

pyrotinib 400 mg once daily; Capecitabine 1000 mg/m2 per day on day 1 through 14, every 21 days.

Pyrotinib plus capecitabine

Eligibility Criteria

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

You may qualify if:

• Pathologically confirmed HER2 positive patients with locally advanced or metastatic breast cancer: HER2 IHC 3+, or HER2 IHC 2+ and FISH detection gene amplification
• Aged ≥18 and ≤70 years.
• ECOG performance status of 0 to 1.
• Life expectancy of more than 12 weeks;
• At least one measurable lesion exists(RECIST 1.1)
• 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).
• 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）
• Known hormone receptor status
• 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
• Patients with adequate organ function before enrollment:
• ANC≥1.5×10\^9/L
• PLT≥100×10\^9/L
• Hb≥90 g/L
• TBIL≤1.5×ULN

You may not qualify if:

• Patients with meningeal metastasis and / or spinal cord metastasis;
• Patients unable to swallow, with chronic diarrhea, intestinal obstruction, or multiple factors that affect drug use and absorption;
• Patients with malignant serious effusion which cannot be controlled by drainage or other methods;
• Less than 4 weeks from the last treatment in last clinical trial;
• Known dihydropyrimidine dehydrogenase (DPD) deficiency;
• Receiving any other antitumor therapy;
• 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;
• Received radiotherapy, surgery (excluding local puncture) within 4 weeks prior to enrollment; received anti-tumor endocrine therapy after entering the screening period;
• Previous or ongoing use of HER2-targeted tyrosine kinase inhibitors (lapatinib, neratinib or pyrotinib);
• Previous use of capecitabine or capecitabine not tolerated, except that capecitabine efficacy cannot be judged or capecitabine discontinuation for 3 months or more;
• Patients with serious heart disease;
• Allergy to pyrotinib; history of immunodeficiency, including HIV positive, active HBV/HCV or other acquired, congenital immunodeficiency disease, or organ transplantation history;
• Known history of neurological or psychiatric disease, including epilepsy or dementia;
• 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;
• 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;

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, 200032, China

Location

Related Publications (1)

• Cao J, Teng Y, Li H, Zhang L, Ouyang Q, Xie W, Pan Y, Song Z, Ling X, Wu X, Xu J, Li L, Ren L, Wang H, Zhou D, Luo J, Hu X. Pyrotinib plus capecitabine for trastuzumab-resistant, HER2-positive advanced breast cancer (PICTURE): a single-arm, multicenter phase 2 trial. BMC Med. 2023 Aug 9;21(1):300. doi: 10.1186/s12916-023-02999-0.

  PMID: 37559142 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Capecitabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Xichun Hu

  Department of Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: June 27, 2019
• First Posted: June 28, 2019
• Study Start: June 26, 2019
• Primary Completion: May 31, 2023
• Study Completion: December 31, 2023
• Last Updated: December 8, 2022

Record last verified: 2022-12

Locations

CN (1)