Exploring Whether Disease-free Intervals Can Guide Endocrine Combined Targeted Therapy for ER+/HER2+ Advanced Breast Cancer (T-sunflower)

This study is a prospective, single-arm, phase II clinical study for patients with ER+/HER2+ advanced breast cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Trastuzumab; Drug: pyrotinib; Drug: Dalpiciclib; Drug: fulvestrant

Detailed Description

Patients with ER+/HER2+ advanced breast cancer are planned to be enrolled. Patients will receive first-line endocrine therapy combined with anti-HER2 therapy. The main purpose is to evaluate whether disease-free intervals can guide first-line endocrine combined targeted therapy for ER+/HER2+ advanced breast cancer.

• Study Type: Interventional
• Enrollment (Anticipated): 126
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan University Shanghai Cancer Center Shanghai, China, 200032

Participation Criteria

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 and ≤ 75 years old;

• Histologically confirmed ER + / HER2- invasive breast cancer (specific definition: immunohistochemical detection of ER> 10% tumor cell positive is defined as ER positive, HER2 3+ or HER2 amplification followed by FISH detection);
• Stage IV breast cancer or recurrent metastatic breast cancer;
• Patients had received no previous chemotherapy or targeted therapy for metastatic disease
• At least one lesion (measurable and/or non-measurable) that has not previously received radiation therapy
• Normal heart function, normal ECG and LVEF ≥ 55%;
• Has adequate bone marrow function: absolute neutrophil count > 1.5x10ˆ9 /L; platelet count > 75x10ˆ9 /L, hemoglobin > 9g/dL;
• Has adequate liver function and kidney function: TBIL ≤1.5 times of the normal upper limit；ALT and AST ≤3 times of the normal upper limit；if liver metastases，then ALT and AST≤ 5 times of the normal upper limit；serum creatinine ≤1.5 times of the normal upper limit; Child-Pugh A/B（≤9 score）
• 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) for metastatic disease
• CNS metastases
• Significant cardiovascular disease(including congestive heart failure, angina pectoris, myocardial infarction or ventricular arrhythmia in the last 6 months);
• is pregnant or breast feeding;
• Malignant tumors in the past five years (except cured skin basal cell carcinoma and cervical carcinoma in situ).
• Positive test for human immunodeficiency virus
• Active hepatitis B or hepatitis C
• Rapid progression of the disease, researchers judge that endocrine combination targeted therapy is not suitable, including the number of liver metastases exceeding 10 or the maximum diameter of a single liver metastases ≥ 10 cm, symptomatic thoraco-ascites, etc.;
• Subjects with uncontrolled lung disease, severe infection, active gastrointestinal ulcer, coagulopathy, severe uncontrolled diabetes, connective tissue disease or inhibition of bone marrow function who cannot tolerate therapy;

• Current use or anticipated need for food or drugs that are known strong CYP3A4 (cytochrome P450 3A4) inhibitors or inducers.

  1. Strong CYP3A inhibitors, including, boceprevir, clarithromycin, conivaptan, delavirdine, indinavir, itraconazole, ketoconazole, lopinavir, mibefradil, miconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, suboxone, telaprevir, telithromycin, voriconazole, and grapefruit, grapefruit juice or any product containing grapefruit.
  2. Strong CYP3A inducers, including carbamazepine, phenytoin, primidone, rifampin, rifapentin, and St. John's wort.
• Moderate infection occurs within 4 weeks before the first administration (e.g. intravenous drip of antibiotics, antifungal or antiviral drugs according to clinical criteria), fever of unknown origin occurs during the screening period/before the first administration.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: T-sunflower group; Patients will be treated with Trastuzumab, Pyrotinib, Dalpiciclib plus Fulvestrant.	Drug: Trastuzumab; 8 mg/kg loading dose IV, then 6 mg/kg IV, every 3 weeks; Drug: pyrotinib; Pyrotinib 320mg, PO daily, continuously; Drug: Dalpiciclib; Dalpiciclib will be given at the dose of 125 mg po q.d. x 21 every 4 weeks; Drug: fulvestrant; Fulvestrant will be given intramuscle at the dose of 500 mg every 4 weeks (with an additional 500 mg dose given two weeks after the initial dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 completion of study (approximately 5 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 completion of study (approximately 5 years)
CBR	the percentage of subjects with CR+PR+SD and last more than 24 weeks in all of the	Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the completion of study (approximately 5 years)
DOR	Duration of 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 completion of study (approximately 5 years)

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2022
• Primary Completion (Anticipated): September 1, 2024
• Study Completion (Anticipated): March 1, 2026

Study Registration Dates

• First Submitted: August 18, 2022
• First Submitted That Met QC Criteria: October 11, 2022
• First Posted (Actual): October 13, 2022

Study Record Updates

• Last Update Posted (Actual): October 13, 2022
• Last Update Submitted That Met QC Criteria: October 11, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Immunological; Hormone Antagonists; Estrogen Antagonists; Estrogen Receptor Antagonists; Trastuzumab; Fulvestrant
• Other Study ID Numbers: FUSCC-T-sunflower

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No