Breast CancerPhase 2MULANNCT04355858
Molecularly Targeted Umbrella Study in Luminal Advanced Breast Cancer
A Phase 2 study testing SHR7390, Famitinib and SHR3162 in people with Breast Cancer and Metastatic Cancer, run by Fudan University at 1 site in China.
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years, women only
- Conditions the study is for
- Breast Cancer, Metastatic Cancer
- What is being tested?
- SHR7390, Famitinib and SHR3162
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 319 participants
- Where
- 1 siteChina
- Study dates
- 1 May 2020to 1 Apr 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Cancer Hospital Affiliated to Fudan University
Shanghai, Shanghai Municipality, 200032
Zhimin Shao, MD, PhD, +86-021-64175590 ext. 8888, zhimingshao@yahoo.com
About this study
Official title: 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.
Read the 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.
- Conditions
- Breast Cancer, Metastatic Cancer
- Being tested
- SHR7390, Famitinib, SHR3162, Pyrotinib, Capecitabine
- Keywords
- first-line therapy
- Medical subject headings
- Breast Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SHR7390Drug
MEK1/2 inhibitor
FamitinibDrug
Multi-target tyrosine kinase inhibitor
SHR3162Drug
PARP inhibitor
PyrotinibDrug
HER1 / HER2 receptor tyrosine kinase inhibitor
CapecitabineDrug
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.
SHR1210Drug
PD-1 antibody
EverolimusDrug
mTOR inhibitor
Nab paclitaxelDrug
Albumin bound paclitaxel
SHR2554Drug
EZH2 inhibitor
SHR3680Drug
AR inhibitor
SHR6390Drug
CDK4/6 inhibitor
SHR1701Drug
anti-PD-L1/TGF-βRII bifunctional fusion protein
SERDDrug
Fulvestrant
AIDrug
aromatase inhibitor
VEGFiDrug
Bevacizumab
| Study group | Role | What they receive |
|---|---|---|
| NF1 mutated | Experimental | If a patient were NF1 mutated, she would receive SHR7390(MEK1/2 inhibitor) and Faminitib. Receives: Drug: SHR7390; Drug: Famitinib |
| gBRCA mutated | Experimental | If a patient were gBRCA mutated, she would receive SHR3162 (PARP inhibitor)and SHR6390(CDK4/6 inhibitor) . Receives: Drug: SHR3162; Drug: SHR6390 |
| HER2 activated mutated | Experimental | 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. Receives: Drug: Pyrotinib; Drug: Capecitabine |
| PDGFRb mutated | Experimental | If a patient were PDGFRb mutated, she would receive Faminitib. Receives: Drug: Famitinib |
| CD8 ≥10% | Experimental | 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. Receives: Drug: Famitinib; Drug: SHR1210; Drug: Nab paclitaxel; Drug: SHR6390; Drug: SHR1701; Drug: SERD; Drug: AI; Drug: VEGFi |
| PAM pathway mutated | Experimental | If a patient had any PAM pathway mutation, she would receive Everolimus(mTOR inhibitor) combined with nab-paclitaxel. Receives: Drug: Everolimus; Drug: Nab paclitaxel |
| AR≥10% | Experimental | If a patient's IHC showed AR≥10% , she would receive SHR2554(EZH2 inhibitor) and SHR3680(AR inhibitor). Receives: Drug: SHR2554; Drug: SHR3680 |
| Epigenetic Cohort | Experimental | In this cohort, a patient would receive SHR2554(EZH2 inhibitor) and SHR3162 (PARP inhibitor). Receives: Drug: SHR3162; Drug: SHR2554 |
| Combined Immunity Cohort | Experimental | In this cohort, a patient would receive SHR6390(CDK4/6 inhibitor) combined with SHR1701(anti-PD-L1/TGF-βRII bifunctional fusion protein) . Receives: Drug: SHR6390; Drug: SHR1701 |
What is being measured
The primary outcome is the main question the study is designed to answer.
ORR
The proportion of participants whose best outcome is complete remission or partial remission (according to RECIST1.1)
Measured: 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 outcomes (3)
CBR
the percentage of subjects with CR+PR+SD and last more than 24 weeks in all of the evaluable subjects
Measured: 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)
PFS
time to progressive disease (according to RECIST1.1)
Measured: 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 to death due to any cause
Measured: Randomization to death from any cause, through the end of study (approximately 5 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2020
- Study start1 May 2020
- Primary completion1 May 2023 (estimated)
- Study completion1 Apr 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Fudan UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 319 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhimin Shao, Fudan University
- Investigators
- Zhi-Ming Shao, Principal investigator, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04355858
- Sponsor's protocol ID
- SCHBCC-N029
- Acronym
- MULAN
- Status last verified
- Jul 2022
- First submitted
- 17 Apr 2020
- Last updated
- 26 Jul 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Chen MK. Efficacy of PARP inhibition combined with EZH2 inhibition depends on BRCA mutation status and microenvironment in breast cancer. FEBS J. 2021 May;288(9):2884-2887. doi: 10.1111/febs.15730. Epub 2021 Feb 11.
PubMed 33570247
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Precision Treatment of Luminal Advanced Breast Cancer Based on Molecular Subtyping
- ClinicalTrials.gov ID
- NCT04355858
- Acronym / sponsor ID
- MULAN / SCHBCC-N029
- Conditions
- Breast Cancer, Metastatic Cancer
- Keywords
- first-line therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 319 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- 1 May 2020 (actual)
- Primary completion
- 1 May 2023 (estimated)
- Study completion
- 1 Apr 2025 (estimated)
- First posted
- 21 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| NF1 mutated | Experimental | Drug: SHR7390, Drug: FamitinibIf a patient were NF1 mutated, she would receive SHR7390(MEK1/2 inhibitor) and Faminitib. |
| gBRCA mutated | Experimental | Drug: SHR3162, Drug: SHR6390If a patient were gBRCA mutated, she would receive SHR3162 (PARP inhibitor)and SHR6390(CDK4/6 inhibitor) . |
| HER2 activated mutated | Experimental | Drug: Pyrotinib, Drug: CapecitabineIf 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. |
| PDGFRb mutated | Experimental | Drug: FamitinibIf a patient were PDGFRb mutated, she would receive Faminitib. |
| CD8 ≥10% | Experimental | Drug: Famitinib, Drug: SHR1210, Drug: Nab paclitaxel, Drug: SHR6390, Drug: SHR1701, Drug: SERD, Drug: AI, Drug: VEGFiIn 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. |
| PAM pathway mutated | Experimental | Drug: Everolimus, Drug: Nab paclitaxelIf a patient had any PAM pathway mutation, she would receive Everolimus(mTOR inhibitor) combined with nab-paclitaxel. |
| AR≥10% | Experimental | Drug: SHR2554, Drug: SHR3680If a patient's IHC showed AR≥10% , she would receive SHR2554(EZH2 inhibitor) and SHR3680(AR inhibitor). |
| Epigenetic Cohort | Experimental | Drug: SHR3162, Drug: SHR2554In this cohort, a patient would receive SHR2554(EZH2 inhibitor) and SHR3162 (PARP inhibitor). |
| Combined Immunity Cohort | Experimental | Drug: SHR6390, Drug: SHR1701In this cohort, a patient would receive SHR6390(CDK4/6 inhibitor) combined with SHR1701(anti-PD-L1/TGF-βRII bifunctional fusion protein) . |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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)
Key exclusion criteria (6 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SHR7390MEK1/2 inhibitor | Drug | NF1 mutated |
| FamitinibMulti-target tyrosine kinase inhibitor | Drug | CD8 ≥10%, NF1 mutated, PDGFRb mutated |
| SHR3162PARP inhibitor | Drug | Epigenetic Cohort, gBRCA mutated |
| PyrotinibHER1 / HER2 receptor tyrosine kinase inhibitor | Drug | HER2 activated mutated |
| CapecitabineIn 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. | Drug | HER2 activated mutated |
| SHR1210PD-1 antibody | Drug | CD8 ≥10% |
| EverolimusmTOR inhibitor | Drug | PAM pathway mutated |
| Nab paclitaxelAlbumin bound paclitaxel | Drug | CD8 ≥10%, PAM pathway mutated |
| SHR2554EZH2 inhibitor | Drug | AR≥10%, Epigenetic Cohort |
| SHR3680AR inhibitor | Drug | AR≥10% |
| SHR6390CDK4/6 inhibitor | Drug | CD8 ≥10%, Combined Immunity Cohort, gBRCA mutated |
| SHR1701anti-PD-L1/TGF-βRII bifunctional fusion protein | Drug | CD8 ≥10%, Combined Immunity Cohort |
| SERDFulvestrant | Drug | CD8 ≥10% |
| AIaromatase inhibitor | Drug | CD8 ≥10% |
| VEGFiBevacizumab | Drug | CD8 ≥10% |
Primary outcome
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)
3 secondary outcomes
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)
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)
OS
Time frame: Randomization to death from any cause, through the end of study (approximately 5 years)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2022.
- Derived from this study: PubMed 33570247Chen MK. Efficacy of PARP inhibition combined with EZH2 inhibition depends on BRCA mutation status and microenvironment in breast cancer. FEBS J. 2021 May;288(9):2884-2887. doi: 10.1111/febs.15730. Epub 2021 Feb 11.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zhi-Ming Shao principal investigator
Fudan University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SHR7390, Famitinib and SHR3162 in people with Breast Cancer and Metastatic Cancer, run by Fudan University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 26 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Zhi-Ming Shao (86-021-64175590 ext. 8888, zhimingshao@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04355858, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2022.