MULAN: Molecularly Targeted Umbrella Study in Luminal Advanced Breast Cancer

Sponsor

Fudan University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04355858

Collaborator

(none)

319

Enrollment

Location

Arms

Anticipated Duration (Months)

5.4

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Metastatic Cancer	Drug: SHR7390 Drug: Famitinib Drug: SHR3162 Drug: Pyrotinib Drug: Capecitabine Drug: SHR1210 Drug: Everolimus Drug: Nab paclitaxel Drug: SHR2554 Drug: SHR3680 Drug: SHR6390 Drug: SHR1701 Drug: SERD Drug: AI Drug: VEGFi	Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

319 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Precision Treatment of Luminal Advanced Breast Cancer Based on Molecular Subtyping

Actual Study Start Date :

May 1, 2020

Anticipated Primary Completion Date :

May 1, 2023

Anticipated Study Completion Date :

Apr 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: NF1 mutated If a patient were NF1 mutated, she would receive SHR7390(MEK1/2 inhibitor) and Faminitib.	Drug: SHR7390 MEK1/2 inhibitor Drug: Famitinib Multi-target tyrosine kinase inhibitor
Experimental: gBRCA mutated If a patient were gBRCA mutated, she would receive SHR3162 (PARP inhibitor)and SHR6390(CDK4/6 inhibitor) .	Drug: SHR3162 PARP inhibitor Drug: SHR6390 CDK4/6 inhibitor
Experimental: HER2 activated mutated If a patient were HER2 activated mutated and had not previously used capecitabine, she would receive Pyrotinib and Capecitabine , while if the patient have previously used capecitabine, she would only use pyrotinib as a single agent.	Drug: Pyrotinib HER1 / HER2 receptor tyrosine kinase inhibitor Drug: 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.
Experimental: PDGFRb mutated If a patient were PDGFRb mutated, she would receive Faminitib.	Drug: Famitinib Multi-target tyrosine kinase inhibitor
Experimental: CD8 ≥10% In the arm which IHC showed CD8 ≥10%, this arm will be subdivided into 6 sub-arms, in which Arm 5A-4D, we choose the patients who had CDK4/6 inhibitor before while in Arm 5E, we choose the patients who secondarily resistant to adjuvant endocrine therapy , and in Arm 5FF, we choose the patients who is in stage IV without precious treatment or sensitively recurrence. A patient would receive SHR1210(PD-1 antibody) ,nab-paclitaxel and Faminitib in Arm-5A. A patient would receive SHR1210(PD-1 antibody) and VEGF inhibitor in Arm-5B. A patient would receive SHR1701(PD-L1/TGF-βRII inhibitor) in Arm-5C. A patient would receive SHR1701(PD-L1/TGF-βRII inhibitor) and SHR6390(CDK4/6 inhibitor) in Arm-5D. A patient would receive SHR1210(PD-1 antibody) and SHR6390(CDK4/6 inhibitor) and SERD in Arm-5E. A patient would receive SHR1210(PD-1 antibody) and SHR6390(CDK4/6 inhibitor) and AI in Arm-5F.	Drug: Famitinib Multi-target tyrosine kinase inhibitor Drug: SHR1210 PD-1 antibody Drug: Nab paclitaxel Albumin bound paclitaxel Drug: SHR6390 CDK4/6 inhibitor Drug: SHR1701 anti-PD-L1/TGF-βRII bifunctional fusion protein Drug: SERD Fulvestrant Drug: AI aromatase inhibitor Drug: VEGFi Bevacizumab
Experimental: PAM pathway mutated If a patient had any PAM pathway mutation, she would receive Everolimus(mTOR inhibitor) combined with nab-paclitaxel.	Drug: Everolimus mTOR inhibitor Drug: Nab paclitaxel Albumin bound paclitaxel
Experimental: AR≥10% If a patient's IHC showed AR≥10% , she would receive SHR2554(EZH2 inhibitor) and SHR3680(AR inhibitor).	Drug: SHR2554 EZH2 inhibitor Drug: SHR3680 AR inhibitor
Experimental: Epigenetic Cohort In this cohort, a patient would receive SHR2554(EZH2 inhibitor) and SHR3162 (PARP inhibitor).	Drug: SHR3162 PARP inhibitor Drug: SHR2554 EZH2 inhibitor
Experimental: Combined Immunity Cohort In this cohort, a patient would receive SHR6390(CDK4/6 inhibitor) combined with SHR1701(anti-PD-L1/TGF-βRII bifunctional fusion protein) .	Drug: SHR6390 CDK4/6 inhibitor Drug: SHR1701 anti-PD-L1/TGF-βRII bifunctional fusion protein

Outcome Measures

Primary Outcome Measures

ORR [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)]
The proportion of participants whose best outcome is complete remission or partial remission (according to RECIST1.1)

Secondary Outcome Measures

CBR [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)]
the percentage of subjects with CR+PR+SD and last more than 24 weeks in all of the evaluable subjects
PFS [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)]
time to progressive disease (according to RECIST1.1)
OS [Randomization to death from any cause, through the end of study (approximately 5 years)]
time to death due to any cause

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cancer Hospital Affiliated to Fudan University	Shanghai	Shanghai	China	200032

Sponsors and Collaborators

Fudan University

Investigators

Principal Investigator: Zhi-Ming Shao, Fudan University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Zhimin Shao, Professor, Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University

ClinicalTrials.gov Identifier:

NCT04355858

Other Study ID Numbers:

SCHBCC-N029

First Posted:

Apr 21, 2020

Last Update Posted:

Jul 26, 2022

Last Verified:

Jul 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by Zhimin Shao, Professor, Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University

first-line therapy

Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 26, 2022