Molecularly Targeted Umbrella Study in Luminal Advanced Breast Cancer

Breast Cancer Clinical Trial

— MULAN  

Official title:

Precision Treatment of Luminal Advanced Breast Cancer Based on Molecular Subtyping

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04355858
• Other study ID #: SCHBCC-N029
• Status: Recruiting
• Phase: Phase 2
• Start date: May 1, 2020
• Est. completion date: April 1, 2025

Study information

• Verified date: July 2022
• Source: Fudan University
• Contact: Zhi-Ming Shao
• Phone: 86-021-64175590
• Email: zhimingshao[@]yahoo.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a prospective, single-center, open-label, umbrella-shaped phase II clinical study for patients with HR+/HER2- endocrine-resistant advanced breast cancer.

Description:

Seven precision treatment cohorts, which targeting NF1 mutation, gBRCA mutation,HER2 mutation, FDGFRb mutation PAM pathway mutations, CD8 and AR, as long as an epigenetic therapy cohort and a combined immunization cohort were initially set up based on gene expression profiles and molecular pathways. The main purpose is to screen valuable treatment cohorts and prepare for subsequent randomized controlled phase III clinical studies with larger sample size.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 319
• Est. completion date: April 1, 2025
• Est. primary completion date: May 1, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Females =18 years old;

• Histologically confirmed HR + / HER2- invasive breast cancer (specific definition:

immunohistochemical detection of ER> 10% tumor cell positive is defined as ER positive, PR> 10% tumor cell positive is defined as PR positive, ER and / or PR Positive is defined as HR positive; HER2 0-1 + or HER2 is ++ but negative followed by FISH detection, no amplification, defined as HER2 negative);

• Locally advanced breast cancer (incapable of radical local treatment) or recurrent metastatic breast cancer;

• Patients with HR+/HER2- advanced breast cancer who were previously treated with CDK4 / 6 inhibitor except for Arm 5E-5F;

• Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1)

• Has adequate bone marrow function: absolute neutrophil count > 1.5x10ˆ9 /L; platelet count > 75x10ˆ9 /L, hemoglobin > 9g/dL;

• Has adequate liver function: alanine aminotransferase (ALT) =1.5×upper limit of normal (ULN), aspartate aminotransferase (AST) =3×ULN, alkaline phosphatase (AKP) =3×ULN, total bilirubin (TBIL) = 1.5×ULN.

• Has adequate kidney function: serum creatinine =1×ULN.Endogenous creatinine clearance> 50 ml / min (Cockcroft-Gault formula);

• Did not receive radiation, molecular targeted therapy or surgery within 3 weeks before the study began, and has recovered from the acute toxicity of previous treatment (if surgery, the wound has completely healed); no peripheral neuropathy or first degree peripheral neurotoxicity ;

• ECOG score = 2 and life expectancy = 3 months;

• Participants voluntarily joined the study, has signed informed consent before any trial related activities are conducted, has good compliance and has agreed to follow-up.

Exclusion Criteria:

• Treatment with chemotherapy, radiotherapy, immunotherapy or surgery (outpatient clinic surgery excluded)within3 weeks prior to initiation of study treatment(bisphosphonates can be used for bone metastasis);

• Symptomatic, untreated, or actively progressing CNS metastases(glucocorticoids or mannitol needed to control symptoms);

• Significant cardiovascular disease(including congestive heart failure, angina pectoris, myocardial infarction or ventricular arrhythmia in the last 6 months);

• Grade = 1 adverse reactions that are ongoing due to previous treatment. Exceptions to this are hair loss or the investigator's opinion should not be ruled out. Such cases should be clearly documented in the investigator's notes;

• Is pregnant or breast feeding;

• Malignant tumors in the past five years (except cured skin basal cell carcinoma and cervical carcinoma in situ).

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Metastatic Cancer

Intervention

Drug:
• SHR7390
MEK1/2 inhibitor
• Famitinib
Multi-target tyrosine kinase inhibitor
• SHR3162
PARP inhibitor
• Pyrotinib
HER1 / HER2 receptor tyrosine kinase inhibitor
• Capecitabine
In Arm III, if the patient had not previously used capecitabine,she would receive pyrotinib and capecitabine, if the patients have previously used capecitabine, she would only used pyrotinib as a single agent.
• SHR1210
PD-1 antibody
• Everolimus
mTOR inhibitor
• Nab paclitaxel
Albumin bound paclitaxel
• SHR2554
EZH2 inhibitor
• SHR3680
AR inhibitor
• SHR6390
CDK4/6 inhibitor
• SHR1701
anti-PD-L1/TGF-ßRII bifunctional fusion protein
• SERD
Fulvestrant
• AI
aromatase inhibitor
• VEGFi
Bevacizumab

Locations

Country	Name	City	State
China	Cancer Hospital Affiliated to Fudan University	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ORR	The proportion of participants whose best outcome is complete remission or partial remission (according to RECIST1.1)	Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the end of study (approximately 5 years)
Secondary	CBR	the percentage of subjects with CR+PR+SD and last more than 24 weeks in all of the evaluable subjects	Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the end of study (approximately 5 years)
Secondary	PFS	time to progressive disease (according to RECIST1.1)	Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the end of study (approximately 5 years)
Secondary	OS	time to death due to any cause	Randomization to death from any cause, through the end of study (approximately 5 years)