Palbociclib, Trastuzumab,Pyrotinib and Fulvestrant Treatment in Patients With Brain Metastasis From ER/PR Positive, HER-2 Positive Breast Cancer: A Multi-center, Prospective Study in China

NCT04334330 | Unknown Phase 2

• 1 other identifier: SCBCS025
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 2

Brief Summary

The objective of this study is to evaluate the efficacy of combination of palbociclib, trastuzumab and pyrotinib with fulvestrant in ER/PR positive and HER2-positive breast cancer patients with brain metastasis.

Conditions

Breast Cancer; Brain Metastases

Keywords

breast cancer, brain metastasis, Palbociclib, CDK4/6 inhibitor, pyrotinib, fulvestrant, trastuzumab, HER2-positive, ER/PR positive, hormonal receptor positive

Outcome Measures

Primary Outcomes (1)

• Objective response rate in the CNS

  Assess the response rate in the CNS by MRI according to modified Response Assessment in modified RECIST 1.1 criteria. Objective CNS response is defined as at least 30% decrease in the sum of diameters of CNS target lesions in the absence of new lesions (defined as ≥ 6 mm), increased steroid use, progressive neurological symptoms, and progressive extra-CNS disease as assessed by RECIST 1.1. Confirmatory scans are not required.

  Up to 3 years

Secondary Outcomes (5)

• Overall Survival

  Up to 3 years

• Progression Free Survival

  Up to 3 years

• Overall Response Rate

  Up to 3 years

• Time to CNS progression

  Up to 3 years

• Time to radiotherapy

  Up to 3 years

Other Outcomes (1)

• Change in quality of life in patients receiving study drug combination

  At baseline, 2 months and 4 months

Study Arms (1)

Treatment group

EXPERIMENTAL

Drug: Palbociclib, Trastuzumab, Pyrotinib and Fulvestrant

Interventions

Palbociclib, Trastuzumab, Pyrotinib and Fulvestrant DRUG

ER/PR positive, HER2-positive breast cancer patients with brain metastatic lesions receive palbociclib PO daily on days 1-21, combined with trastuzumab IV every three weeks, pyrotinib PO daily and fulvestrant IM every 4 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Treatment group

Eligibility Criteria

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

You may qualify if:

• Age greater than 18 years old
• Female patients aged 18 years or older
• Histologically confirmed ER/PR positive, HER2-positive metastatic breast cancer (ER/PR≥1% by IHC; HER-2 3+ by immunohistochemistry (IHC); if IHC score of 2, fluorescence in situ hybridization (FISH) ratio must be greater than 2.0; if FISH less than 2.0, HER2 copy number must be greater than 6; NOTE: Brain lesions are not required to have pathologic confirmation)
• Patients must have a life expectancy of at least 12 weeks at the time of registration
• Eastern Cooperative Oncology Group (ECOG) performance status \>= 2
• Measurable disease in the brain, defined as at least 1 lesion measuring \>= 10 mm on MRI at the time of registration
• If patients are on corticosteroids, they must have been on a stable or decreasing dose \>= 5 days prior to obtaining their baseline gadolinium (Gd)-magnetic resonance imaging (MRI) of brain; this MRI is to be obtained within 28 days of registration; NOTE: If patient needs escalation of steroids prior to therapy, or are on unstable doses of steroids they are not eligible
• Patients who have a history of hypersensitivity reaction to one of the compounds or incorporated substances used in this protocol; AND/OR patients who have had prior exposure to fulvestrant, everolimus, pyrotinib or CDK4/6 inhibitors and had a disease progression during treatment are not eligible.
• Patients must not have received systemic therapy within 2 weeks of initiating palbociclib; NOTE: For patients on trastuzumab, they can remain on the drug; no break or washout period required
• Patients must exhibit adequate bone marrow, liver, and renal function, within 14 days prior to registration, defined as:
• Absolute neutrophil count (ANC) \>= 1,000/mm\^3 (growth factor support is permitted)
• Platelets \>= 50,000/mm\^3 (may be reached by transfusion)
• Hemoglobin \>= 10 gm/dl (may be reached by transfusion)
• Glutamate pyruvate transaminase (GPT)/glutamate oxaloacetate transaminase (GOT) \< 3 x upper limit of normal (ULN) (or \< 5 x ULN in case of liver metastasis)
• Bilirubin \< 3 x ULN (or \< 5 x ULN in case of liver metastasis)

You may not qualify if:

• Any uncontrolled neurological symptom attributed to CNS metastasis
• Brain metastasis must not be impending herniation or other significant vasogenic edema requiring increasing steroid doses; lesions must not have frank hemorrhage
• Patients with leptomeningeal disease are not eligible for participation
• Patients have been treated with WBRT. The selected intracranial target lesion has received local treatment (surgical resection or SRS). Acute effects related to surgery or SRS have not recover
• Any significant medical illnesses or infection that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy are not eligible for participation
• Known human immunodeficiency virus (HIV) positive status
• Known active hepatitis B and/or C
• Patients who have a history of hypersensitivity reaction to one of the compounds or incorporated substances used in this protocol; AND/OR patients who have had prior exposure to compounds of similar chemical or biologic composition to palbociclib or lapatinibpyrotinib and PD during treatment are not eligible.
• Patients being treated with any other experimental agents/clinical trials are not eligible for participation; if the patient is on any investigational agent, a wash-out period of minimum 2 weeks prior to registration is mandatory for the patient to be eligible for the study
• Inability to swallow capsules, malabsorption syndrome or gastrointestinal disease that severely affects the absorption of study drugs, major resection of the stomach or small bowel, or gastric bypass procedure
• Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible:
• Ongoing or active infection requiring systemic treatment
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia: except atrial fibrillation (AF) and supraventricular tachycardia (SVT) that are controlled by medication

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (2)

Shusen Wang

Guangzhou, Guangdong, 510060, China

RECRUITING

State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

Related Publications (1)

• Chen D, Xu F, Lu Y, Xia W, Du C, Xiong D, Song D, Shi Y, Yuan Z, Zheng Q, Jiang K, An X, Xue C, Huang J, Bi X, Chen M, Zhang J, Wang S, Hong R. Pyrotinib and trastuzumab plus palbociclib and fulvestrant in HR+/HER2+ breast cancer patients with brain metastasis. NPJ Breast Cancer. 2024 Jun 13;10(1):45. doi: 10.1038/s41523-024-00646-2.

  PMID: 38871705 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Brain Neoplasms

Interventions

palbociclib; Trastuzumab; pyrotinib; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

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: Chief Physician

Study Record Dates

• First Submitted: April 2, 2020
• First Posted: April 6, 2020
• Study Start: December 4, 2020
• Primary Completion: December 30, 2023
• Study Completion: December 31, 2024
• Last Updated: May 2, 2022

Record last verified: 2022-04

Locations

CN (2)