Palbociclib + Letrozole Versus Epirubicin + Cyclophosphamide and Sequential Docetaxel as Neoadjuvant Chemotherapy

NCT04137640 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: Shengjing-LCG003
• Study Type: interventional
• Target: 152
• Locations: 1 country
• Sites: 1

Brief Summary

With the development of neoadjuvant therapy for tumors, neoadjuvant chemotherapy (NAC) has become one of the most common and effective methods for preoperative systemic treatment of locally advanced breast cancer (LABC). Although epirubicin combined with cyclophosphamide and sequential docetaxel has been widely recognized as the first-line NAC for LABC, there are still some inoperable LABCs that are insensitive to chemotherapy and miss the opportunity of surgery, especially those with luminal A and low expression of Ki67. Therefore, neoadjuvant endocrine therapy has important clinical value for such patients. At present, the combination of aromatase inhibitor drugs and cyclin dependent kinase 4/6 can significantly improve the prognosis and survival of LABC compared with aromatase inhibitor monotherapy. However, whether inoperable LABC patients, especially those who are not susceptible to chemotherapy, can choose the combination of aromatase inhibitor drugs and cyclin dependent kinase 4/6 as neoadjuvant endocrine therapy to replace NAC remains unclear. Because the main principle of endocrine therapy is to induce tumor cell cycle arrest, leading to apoptosis of tumor cells, the effect is slower than that of chemotherapy. In addition, whether endocrine therapy can replace chemotherapy as a new adjuvant treatment for patients with inoperable LABC to improve the operability rate has not yet been fully evidenced. Therefore, this trial aims to conduct the prospective randomized controlled phase IV clinical trial of palbociclib combined with letrozole versus epirubicin combined with cyclophosphamide and sequential docetaxel as NAC to prove the efficacy of palbociclib combined with letrozole in postmenopausal estrogen receptor-positive LABC patients with low Ki67 expression.

Conditions

Breast Cancer

Keywords

adjuvant chemotherapy; estrogen receptor; palbociclib; letrozole

Outcome Measures

Primary Outcomes (1)

• Clinical Response

  Clinical response will be evaluated 5 years after treatment according to the regression of tumors. Tumor regression will be assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

  5 years after treatment

Secondary Outcomes (8)

• Breast-conserving rate

  6 months after treatment

• Operable rate

  6 months after treatment

• Ki67 expression in tumor tissues

  Before treatment and 6 months and 5 years after treatment

• Miller-Payne grading system

  Before treatment, 6 months and 5 years after treatment

• Preoperative endocrine prognostic index

  6 months and 5 years after treatment

Study Arms (2)

endocrine group

OTHER

76 postmenopausal estrogen receptor-positive LABC patients with low Ki67 expression will beassigned into endocrine group.

Drug: palbociclib combined with letrozole

chemotherapy group

OTHER

76 postmenopausal estrogen receptor-positive LABC patients with low Ki67 expression will beassigned into chemotherapy group

Drug: epirubicin combined with cyclophosphamide and sequential docetaxel

Interventions

palbociclib combined with letrozole DRUG

Endocrine group will receive palbociclib combined with letrozole: palbociclib (Pfizer Manufacturing Deutschland GmbH, Freiburg, Germany; license number: H20180040) 125 mg/d, every 28 days as a cycle (medication for 3 consecutive weeks and withdrawal for 1 week); letrozole (Novartis Pharma Schweiz AG, Stein, Switzerland; license number: H20140149) 2.5 mg/d, for 6 consecutive months.

Also known as: Endocrine group

endocrine group

epirubicin combined with cyclophosphamide and sequential docetaxel DRUG

Chemotherapy group will receive epirubicin combined with cyclophosphamide and sequential docetaxel: epirubicin (Pfizer Wuxi Pharmaceutical Plant, Wuxi, China; license number: GYZZ H20000496), 90 mg/m2, intravenously, for 120 minutes, once every four weeks, totally four times; cyclophosphamide (Baxter Oncology GmbH, Halle, Germany; license number: H20160468), 600 mg/m2, once every four weeks, totally four times; sequential docetaxel (Sanofi-aventis Deutschland GmbH, Frankfurt am Main, Germany; license number: GYZZ J20150083) 75 mg/m2, intravenously, for 120 minutes, once every four weeks, totally four times.

Also known as: Chemotherapy group

chemotherapy group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• pathological examination confirms estrogen receptor positive, and Ki67 \< 30% in breast cancer patients;
• postmenopausal women;
• tumor size stage ≥ T3, or lymph node stage ≥ N2, or ipsilateral upper extremity edema or the extent of lesions exceeds the scope of radical surgery;
• Karnofsky functional status score ≥ 70;
• normal findings of blood examination, normal liver and kidney functions, and basically normal electrocardiogram results before chemotherapy;
• age range from 18-70 years old.

You may not qualify if:

• history of anti-tumor treatment;
• inflammatory breast cancer or occult breast cancer;
• stage IV breast cancer;
• history of other malignant tumors;
• severe vital organ dysfunction, such as heart, liver and kidney or poor constitution cannot tolerate chemotherapy, or the treatment plan change due to intolerance during chemotherapy;
• cannot comply with the treatment because of mental and neurological diseases;
• dexamethasone contraindications or severe allergies to any drug in NAC;
• receiving NAC, but it is judged to be ineffective after two cycles of treatment, and other programs are forced to be used or chemotherapy is stopped to receive surgery;
• participation in other clinical trials.

Sponsors & Collaborators

• Shengjing Hospital: lead

Study Sites (1)

Shengjing Hospital of China Medical University

Shenyang, Liaoning, 110004, China

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Letrozole; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds

Study Officials

• Caigang Liu, M.D., Ph.D.

  Shengjing Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xi Gu, M.D.

CONTACT

+86 18940255116; jadegx@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 22, 2019
• First Posted: October 24, 2019
• Study Start: July 19, 2021
• Primary Completion: November 30, 2025
• Study Completion (Estimated): May 31, 2026
• Last Updated: July 20, 2021

Record last verified: 2021-07

Locations

CN (1)