Molecularly Targeted Umbrella Study in Luminal Advanced Breast Cancer (MULAN)

July 22, 2022 updated by: Zhimin Shao, Fudan University

Precision Treatment of Luminal Advanced Breast Cancer Based on Molecular Subtyping

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

319

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200032
        • Recruiting
        • Cancer Hospital Affiliated to Fudan University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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: SHR6390
CDK4/6 inhibitor
Drug: SHR3162
PARP 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: SHR6390
CDK4/6 inhibitor
Drug: SERD
Fulvestrant
Drug: AI
aromatase inhibitor
Drug: Nab paclitaxel
Albumin bound paclitaxel
Drug: Famitinib
Multi-target tyrosine kinase inhibitor
Drug: SHR1210
PD-1 antibody
Drug: SHR1701
anti-PD-L1/TGF-βRII bifunctional fusion protein
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ORR
Time Frame: 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)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
PFS
Time Frame: 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)
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)
OS
Time Frame: Randomization to death from any cause, through the end of study (approximately 5 years)
time to death due to any cause
Randomization to death from any cause, through the end of study (approximately 5 years)
CBR
Time Frame: 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
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fudan University

Investigators

  • Principal Investigator: Zhi-Ming Shao, Fudan University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2020

Primary Completion (Anticipated)

May 1, 2023

Study Completion (Anticipated)

April 1, 2025

Study Registration Dates

First Submitted

April 17, 2020

First Submitted That Met QC Criteria

April 17, 2020

First Posted (Actual)

April 21, 2020

Study Record Updates

Last Update Posted (Actual)

July 26, 2022

Last Update Submitted That Met QC Criteria

July 22, 2022

Last Verified

July 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SCHBCC-N029

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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