Mecapegfilgrastim for the Prevention of Dalpiciclib -Induced Neutropenia in Advanced Breast Cancer

Efficacy and Safety of Mecapegfilgrastim for Prophylaxis of Dalpiciclib -Induced Neutropenia in Patients With Advanced HR+/HER2- Breast Cancer: a Open-label, Multicenter, Investigator-initiated, Randomized Controlled Phase II Trial

Neutropenia is a common complication from dalpiciclib. Mecapegfilgramtim (code name HHPG-19K), a long-acting recombinant human granulocyte colony-stimulating factor (rhG-CSF), has been developed. The study aim to evaluate the safety and efficiency of mecapegfilgrastim for prophylaxis of dalpiciclib -induced neutropenia in patients with advanced HR+/HER2- breast cancer.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Mecapegfilgrastim; Drug: dalpiciclib; Drug: exemestane, fulvestrant, letrozole, tamoxifen

• Study Type: Interventional
• Enrollment (Anticipated): 132
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Recruiting
      • 中山大学中山纪念医院
      • Contact: Jieqiong Liu; Phone Number: 8620-43070091; Email: 刘杰琼01@163.com
      • Principal Investigator: 二伟 歌曲
      • Sub-Investigator: Jieqiong 刘

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18.
2. Pathologically confirmed advanced HR+/HER2- breast cancer: there is evidence of focal recurrence or metastasis, which is not suitable for surgical resection or radiotherapy for the purpose of cure.
3. No more than one line of chemotherapy is allowed for patients with recurrent and metastatic diseases.
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
5. Measurable lesions meeting RECIST 1.1 criteria or only bone metastases.
6. For patients with brain metastases, there is need for local treatment, and the brain lesions are stable for ≥ 3 months, and no need for dexamethasone or mannitol.
7. Adequate organ function: (I) adequate hematologic function: hemoglobin ≥90 g/L, absolute neutrophil count (ANC) ≥2.0×109/L, platelet count (PLT) ≥100×109/L; (II) adequate renal and hepatic function.
8. Negative pregnancy test.

Exclusion Criteria:

1. Previous pathological diagnosis of HER2 positive breast cancer.
2. Relapse and metastasis occurred after receiving neoadjuvant endocrine therapy or adjuvant therapy for 2 years, or disease progression or recurrence occurred within 12 months or 12 months after completion of adjuvant endocrine therapy.
3. Previous treatment with cdk4/6 inhibitors.
4. Major surgery, chemotherapy, radiotherapy, any research drug or other anti-cancer treatment within 2 weeks before entering the trial.
5. Any other malignant tumor diagnosed within 3 years before entering the study, except non-melanoma skin cancer, basal cell or squamous cell skin cancer or cervical carcinoma in situ after radical treatment.
6. Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), active hepatitis B (HBV DNA ≥ 1000 IU/ml), hepatitis C (HCV antibody positive and HCV-RNA higher than the detection limit of the analytical method) or combined hepatitis B and hepatitis C co-infection.
7. Within 6 months before entering the study, the following conditions occurred: myocardial infarction, severe / unstable angina pectoris, NYHA grade 2 or above cardiac insufficiency, persistent arrhythmia ≥ grade 2 (according to nci-ctcae version 5.0), atrial fibrillation at any level, coronary / peripheral artery bypass grafting, symptomatic congestive heart failure, cerebrovascular accident (including transient ischemic attack or symptomatic pulmonary embolism).
8. Inability to swallow, intestinal obstruction or other factors affecting drug administration and absorption.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mecapegfilgrastim +dalpiciclib + endocrine therapy; Mecapegfilgrastim / dalpiciclib / Endocrine therapy (exemestane, fulvestrant, letrozole, tamoxifen)	Drug: Mecapegfilgrastim; Mecapegfilgrastim; Drug: dalpiciclib; dalpiciclib; Drug: exemestane, fulvestrant, letrozole, tamoxifen; endocrine therapy
Active Comparator: dalpiciclib + endocrine therapy; dalpiciclib / Endocrine therapy (exemestane, fulvestrant, letrozole, tamoxifen)	Drug: dalpiciclib; dalpiciclib; Drug: exemestane, fulvestrant, letrozole, tamoxifen; endocrine therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of grade ≥3 neutropenia at the end of cycle 2 (each cycle is 28 days)	The incidence of grade ≥3 neutropenia in cycle 2: defined as ANC <1.0×109/L at the end of Cycle 1 (each cycle is 28 days).	at the end of cycle 2 (each cycle is 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of grade ≥3 neutropenia at the end of all cycles (each cycle is 28 days)	The incidence of grade ≥3 neutropenia in cycle 2: defined as ANC <1.0×109/L at the end of All Cycles (each cycle is 28 days).	through study completion, an average of 2 years
Breast-Q scores	Breast-Q scores for patient's quality of life	through study completion, an average of 2 years
Progression-free Survival	Progression-free Survival	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Overall Survival	Overall Survival	From date of randomization until the date of death from any cause, assessed up to 60 months
Relative dose intensity of dalpiciclib	Relative dose intensity of dalpiciclib	through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Collaborators: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: June 1, 2022
• First Submitted That Met QC Criteria: July 17, 2022
• First Posted (Actual): July 19, 2022

Study Record Updates

• Last Update Posted (Actual): April 12, 2023
• Last Update Submitted That Met QC Criteria: April 10, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Hematologic Diseases; Breast Diseases; Agranulocytosis; Leukopenia; Leukocyte Disorders; Breast Neoplasms; Neutropenia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Bone Density Conservation Agents; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Estrogen Receptor Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Letrozole; Fulvestrant; Tamoxifen; Exemestane
• Other Study ID Numbers: SYSKY-2022-105-01

Drug and device information, study documents

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