Molecularly Targeted Umbrella Study in Luminal Advanced Breast Cancer

NCT04355858 | Unknown Phase 2 DMC

• 1 other identifier: SCHBCC-N029
• Study Type: interventional
• Target: 319
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer; Metastatic Cancer

Keywords

first-line therapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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)

• 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)

• OS

  Randomization to death from any cause, through the end of study (approximately 5 years)

Study Arms (9)

NF1 mutated

EXPERIMENTAL

If a patient were NF1 mutated, she would receive SHR7390(MEK1/2 inhibitor) and Faminitib.

Drug: SHR7390; Drug: Famitinib

gBRCA mutated

EXPERIMENTAL

If a patient were gBRCA mutated, she would receive SHR3162 (PARP inhibitor)and SHR6390(CDK4/6 inhibitor) .

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.

Drug: Pyrotinib; Drug: Capecitabine

PDGFRb mutated

EXPERIMENTAL

If a patient were PDGFRb mutated, she would receive Faminitib.

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.

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.

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).

Drug: SHR2554; Drug: SHR3680

Epigenetic Cohort

EXPERIMENTAL

In this cohort, a patient would receive SHR2554(EZH2 inhibitor) and SHR3162 (PARP inhibitor).

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) .

Drug: SHR6390; Drug: SHR1701

Interventions

SHR7390 DRUG

MEK1/2 inhibitor

NF1 mutated

Famitinib DRUG

Multi-target tyrosine kinase inhibitor

CD8 ≥10%; NF1 mutated; PDGFRb mutated

SHR3162 DRUG

PARP inhibitor

Epigenetic Cohort; gBRCA mutated

Pyrotinib DRUG

HER1 / HER2 receptor tyrosine kinase inhibitor

HER2 activated mutated

Capecitabine DRUG

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.

HER2 activated mutated

SHR1210 DRUG

PD-1 antibody

CD8 ≥10%

Everolimus DRUG

mTOR inhibitor

PAM pathway mutated

Nab paclitaxel DRUG

Albumin bound paclitaxel

CD8 ≥10%; PAM pathway mutated

SHR2554 DRUG

EZH2 inhibitor

AR≥10%; Epigenetic Cohort

SHR3680 DRUG

AR inhibitor

AR≥10%

SHR6390 DRUG

CDK4/6 inhibitor

CD8 ≥10%; Combined Immunity Cohort; gBRCA mutated

SHR1701 DRUG

anti-PD-L1/TGF-βRII bifunctional fusion protein

CD8 ≥10%; Combined Immunity Cohort

SERD DRUG

Fulvestrant

CD8 ≥10%

AI DRUG

aromatase inhibitor

CD8 ≥10%

VEGFi DRUG

Bevacizumab

CD8 ≥10%

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Cancer Hospital Affiliated to Fudan University

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

Related Publications (1)

• 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.

  PMID: 33570247 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

famitinib; fluzoparib; pyrotinib; Capecitabine; camrelizumab; Everolimus; Taxes; SHR-1701

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Sirolimus; Macrolides; Lactones; Organic Chemicals; Economics; Health Care Economics and Organizations

Study Officials

• Zhi-Ming Shao

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhi-Ming Shao

CONTACT

86-021-64175590; zhimingshao@yahoo.com

Zhong-Hua Wang

CONTACT

+86 021-64175590; zhonghuawang95@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery

Study Record Dates

• First Submitted: April 17, 2020
• First Posted: April 21, 2020
• Study Start: May 1, 2020
• Primary Completion: May 1, 2023
• Study Completion: April 1, 2025
• Last Updated: July 26, 2022

Record last verified: 2022-07

Locations

CN (1)