Clinical trial NCT03123770: Efficacy and Safety of Neoadjuvant DC-T in Breast Cancer Patients
Official title: The Efficacy and Safety of Neoadjuvant Pegylated Liposomal Doxorubicin Plus Cyclophosphamide Followed by Docetaxel in Breast Cancer Patients: A Multicentric, Open-label, Non-randomized Concurrent Control, Non-inferiority Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Breast Cancer
Keywords: Breast cancer
Neoadjuvant Chemotherapy
Pegylated liposomal doxorubicin
PLD
Lead sponsor: Zhejiang University
Sponsor class: OTHER
Collaborators: name: Second Affiliated Hospital, School of Medicine, Zhejiang University
name: First Affiliated Hospital of Zhejiang University
name: Sir Run Run Shaw Hospital
name: Women's Hospital School Of Medicine Zhejiang University
name: Zhejiang Cancer Hospital
name: Zhejiang Provincial People's Hospital
name: Zhejiang Provincial Hospital of TCM
name: First People's Hospital of Hangzhou
name: Hangzhou Hospital of Traditional Chinese Medicine
name: First Affiliated Hospital of Wenzhou Medical University
name: Ningbo No. 1 Hospital
name: Jinhua Central Hospital
First posted: 2017-04-21
Enrollment: 384
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multicentric, open-label,non-randomized concurrent control, 1:1 match,non-inferiority trial that assesses the efficacy and safety of neoadjuvant chemotherapy regimen DC-T and EC-T in breast cancer patients.

Detailed description: OBJECTIVES: Determine the efficacy and safety of neoadjuvant chemotherapy regimen DC-T and EC-T in suitable breast cancer patients.

Participants are randomized to 1 of 2 treatment arms.

1. Arm I: Participants receive pegylated liposomal doxorubicin plus cyclophosphamide followed by docetaxel before surgery.
2. Arm II: Participants receive epirubicin plus cyclophosphamide followed by docetaxel before surgery.

Patients in arms I and II will undergo physical examination, MRI, estimating of side effects every 4 cycles referring to RECIST (Response Evaluation Criteria In Solid Tumor) guideline. To adjust for potential bias, patients in DC-T arm were matched 1:1 to patients in the EC-T arm based on Her-2 and ER status. After finishing 8 cycles of neoadjuvant chemotherapy, every patient will receive mastectomy or breast-conserving surgery and then assess the pCR rate of primary lesion and axillary lymph nodes. Adjuvant radiotherapy and endocrine therapy will be taken if necessary. Every patient will be followed-up for five years to monitor survival condition.

Eligibility criteria: Inclusion Criteria:

1. Women aged : 18\~70 years.
2. WHO (ECOG) performance status 0-2.
3. Patients who have read and understand the informed consent form and have given written informed consent.
4. Diagnosed as invasive breast cancer by core biopsy
5. Diagnosed pre-surgically as (cTNM Staging)Stage II-III and suit for neoadjuvant chemotherapy.
6. Patients had previously not received chemotherapy，radiotherapy or biotherapy.
7. Normal organ function，meeting the requirement of laboratory testing below:

   * WBC≥4.0×109/L,
   * NEU≥1.5×109/L,
   * PLT≥100×109/L,
   * HB ≥10g/dL,
   * Scr≤1.5× ULN,
   * AST ≤2.5×ULN,
   * ALT ≤2.5×ULN,
   * TDIL≤1.5×ULN.
8. Patients with measurable lesion assessed by imaging using the RECIST (Response Evaluation Criteria In Solid Tumor) guideline，（long diameter of primary lesion ≥1cm or minor diameter of lymph node ≥1.5cm）；

Exclusion Criteria:

1. Pregnant or lactating women were excluded.
2. History of receiving organ transplantation（including Autologous bone marrow transplantation and peripheral hematopoietic stem-cell transplantation).
3. Dysfunction of peripheral nerve system caused by other diseases or history of either severe mental disorder or central nervous system disorders.
4. Uncontrolled infection or severe peptic ulcer need treatment.
5. Severe hepatic disease（such as hepatic cirrhosis),nephrosis,respiratory disease or uncontrolled diabetes.
6. Patients with malignancies (other than breast cancer) within the last 5 years, except for adequately treated in situ carcinoma of the cervix or basal cell carcinoma of the skin.
7. Significant abnormal EKG or cardiac disease with drastic symptoms like congestive heart failure or severe coronary disease or uncontrolled arrhythmia or myocardial infarction within 12 months or NYHA level III-IV or LVEF\<55% .
8. Be allergic to test drugs.

Primary outcomes:
measure: Pathological complete response rate
timeFrame: 5 years
Secondary outcomes:
measure: Side effects
timeFrame: 5 years
measure: Overall survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: Cancer institute
state: Zhejiang
Study officials:
affiliation: Second Affiliated Hospital of Zhejiang University School of Medicine
name: Huang Jian, Dr
role: STUDY_CHAIR
References:
citation: O'Brien ME, Wigler N, Inbar M, Rosso R, Grischke E, Santoro A, Catane R, Kieback DG, Tomczak P, Ackland SP, Orlandi F, Mellars L, Alland L, Tendler C; CAELYX Breast Cancer Study Group. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol. 2004 Mar;15(3):440-9. doi: 10.1093/annonc/mdh097.
citation: Vici P, Pizzuti L, Gamucci T, Sergi D, Conti F, Zampa G, Del Medico P, De Vita R, Pozzi M, Botti C, Di Filippo S, Tomao F, Sperduti I, Di Lauro L. Non-pegylated liposomal Doxorubicin-cyclophosphamide in sequential regimens with taxanes as neoadjuvant chemotherapy in breast cancer patients. J Cancer. 2014 Apr 25;5(6):398-405. doi: 10.7150/jca.9132. eCollection 2014.
citation: Gil-Gil MJ, Bellet M, Morales S, Ojeda B, Manso L, Mesia C, Garcia-Martinez E, Martinez-Janez N, Mele M, Llombart A, Pernas S, Villagrasa P, Blasco C, Baselga J. Pegylated liposomal doxorubicin plus cyclophosphamide followed by paclitaxel as primary chemotherapy in elderly or cardiotoxicity-prone patients with high-risk breast cancer: results of the phase II CAPRICE study. Breast Cancer Res Treat. 2015 Jun;151(3):597-606. doi: 10.1007/s10549-015-3415-2. Epub 2015 May 16.
citation: Uriarte-Pinto M, Escolano-Pueyo A, Gimeno-Ballester V, Pascual-Martinez O, Abad-Sazatornil MR, Agustin-Ferrandez MJ. Trastuzumab, non-pegylated liposomal-encapsulated doxorubicin and paclitaxel in the neoadjuvant setting of HER-2 positive breast cancer. Int J Clin Pharm. 2016 Apr;38(2):446-53. doi: 10.1007/s11096-016-0278-5. Epub 2016 Mar 7.