Neoadjuvant Aromatase Inhibitor(AI) With Ovarian Suppression Versus Chemotherapy in Premenopausal Breast Cancer Patients

NCT02532400 | Terminated Phase 3 DMC

• 1 other identifier: RJBC1505
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

To compare the efficacy and safety of neoadjuvant aromatase inhibitor plus ovarian suppression with chemotherapy in premenopausal patients with hormone receptor-positive breast cancer.

Conditions

Breast Cancer

Keywords

Breast Neoplasms; Neoadjuvant Endocrine Therapy; Ovarian Function Suppression; Neoadjuvant chemotherapy

Outcome Measures

Primary Outcomes (1)

• Overall response rate(ORR)

  Overall response rate(ORR) is defined as complete response rate plus partial response rate.

  up to 7 months

Secondary Outcomes (6)

• Pathological complete response(pCR)

  up to 7 months

• Breast conserving surgery(BCS) rate

  up to 7 months

• Incidence of neutropenia fever

  participants will be followed during the six months of neoadjuvant therapy

• Incidence of hot flushes/flashes

  participants will be followed during the six months of neoadjuvant therapy

• Incidence of osteoporosis

  participants will be followed during the six months of neoadjuvant therapy

Study Arms (2)

Neoadjuvant endocrine therapy

EXPERIMENTAL

Six months of exemestane or anastrozole plus goserelin.

Drug: Neoadjuvant endocrine therapy

Neoadjuvant chemotherapy

ACTIVE COMPARATOR

Six cycles of docetaxel plus epirubicin and cyclophosphamide(TEC).

Drug: Neoadjuvant chemotherapy

Interventions

Neoadjuvant endocrine therapy DRUG

Goserelin: 3.6mg, d1, hypodermic injection , q28d\*7 plus exemestane: 25mg, po, qd\*24w, or anastrozole: 1mg, po, qd\*24w

Also known as: Goserelin and AI

Neoadjuvant endocrine therapy

Neoadjuvant chemotherapy DRUG

Docetaxel: 75mg/m2, d1, q3w\*6, Epirubicin 75mg/m2, d1, q3w\*6 and Cyclophosphamide: 500mg/m2, d1, q3w\*6

Also known as: TEC

Neoadjuvant chemotherapy

Eligibility Criteria

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

You may qualify if:

• Written informed consent
• Women aged ≥ 18 years
• Histologically confirmed invasive breast cancer
• American Joint Committee on Cancer (AJCC) stage: ⅡA-ⅢC, no evidence of metastasis
• At least one measurable disease in breast and/or axilla
• ER and/or progesterone receptor(PgR) positive(≥10% of the cells by IHC)
• HER2 negative(by IHC and/or FISH)
• Premenopause status (estradiol in premenopausal range or with normal menstrual cycle in the past 6 months with no use of hormonal drugs)
• Eastern Cooperative Oncology Group（ECOG）score 0-1, an estimated life expectancy of at least 12 months
• Adequate bone marrow function: Leukocyte ≥ 3.0\*109/L; Neutrophil ≥ 1.5\*109/L; Hb ≥ 100g/L; Platelet(PLT） ≥ 80\*109/L
• Adequate liver, renal function and coagulation function: Alanine transaminase（ALT） and/or Aspartate transaminase（AST）≤ 1.5 upper normal limit（UNL）, total bilirubin ≤upper normal limit, creatinine ≤ 110umol/L, Creatinine clearance \> 60ml/min, blood urea nitrogen（BUN） ≤ 7.1mmol/L, activated partial thromboplastin time（APTT） ≤ 1.5 upper normal limit（UNL）
• Women with child-bearing potential must have a negative pregnancy test (urine or serum) within 7 days of drug administration and agree to use an acceptable method of birth control to avoid pregnancy for the duration of the study
• Serological records of hepatitis B virus（HBV）and hepatitis C virus（HCV） testing.

You may not qualify if:

• Stage IV breast cancer
• Prior systemic or loco-regional treatment of breast cancer
• Any anti-neoplastic treatment within 28 days before the beginning of study
• Known severe hypersensitivity to any drugs in this study
• History of malignancy within 5 years except carcinoma in situ of cervix or skin basal cell carcinoma that had received adequate treatment
• Peripheral neuropathy ≥ 2°, according to National Cancer Institute(NCI) Common Terminology Criteria for Adverse Events(CTCAE)(Version 4.0)
• Any cardiac or pulmonary dysfunction defined as following:
• (1) ≥ 3° symptomatic congestive heart failure (CHF) according to NCI CTCAE(Version 4.0) or ≥ 2° CHF according to New York Heart Association（NYHA）
• (2) Angina that needs anti-anginal drugs, advanced conduction abnormality or significant vascular disease
• (3) Uncontrolled high-risk arrhythmia: atrial tachycardia that silent heart rate \>100/min, significant ventricular arrythmia or advanced atrioventricular block(2° type II atrioventricular or 3° atrioventricular block)
• (4) Poorly controlled hypertension (systolic BP \> 180 mmHg or diastolic BP \> 100 mmHg)
• (5) Transmural myocardial infarction in EKG
• (6) Long-term oxygen therapy
• \. Uncontrolled severe systemic disease(clinically significant cardiovascular disease，pulmonary disease or metabolic disease, wound healing disorder, ulcer, severe infection)
• \. Pregnant or breast feeding

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Ruijin Hospital

Shanghai, Shanghai Municipality, 200025, China

Location

Related Publications (9)

• Coates AS, Winer EP, Goldhirsch A, Gelber RD, Gnant M, Piccart-Gebhart M, Thurlimann B, Senn HJ; Panel Members. Tailoring therapies--improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015. Ann Oncol. 2015 Aug;26(8):1533-46. doi: 10.1093/annonc/mdv221. Epub 2015 May 4.

  PMID: 25939896 BACKGROUND

• Mauri D, Pavlidis N, Ioannidis JP. Neoadjuvant versus adjuvant systemic treatment in breast cancer: a meta-analysis. J Natl Cancer Inst. 2005 Feb 2;97(3):188-94. doi: 10.1093/jnci/dji021.

  PMID: 15687361 BACKGROUND

• von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, Gerber B, Eiermann W, Hilfrich J, Huober J, Jackisch C, Kaufmann M, Konecny GE, Denkert C, Nekljudova V, Mehta K, Loibl S. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012 May 20;30(15):1796-804. doi: 10.1200/JCO.2011.38.8595. Epub 2012 Apr 16.

  PMID: 22508812 BACKGROUND

• Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, Bonnefoi H, Cameron D, Gianni L, Valagussa P, Swain SM, Prowell T, Loibl S, Wickerham DL, Bogaerts J, Baselga J, Perou C, Blumenthal G, Blohmer J, Mamounas EP, Bergh J, Semiglazov V, Justice R, Eidtmann H, Paik S, Piccart M, Sridhara R, Fasching PA, Slaets L, Tang S, Gerber B, Geyer CE Jr, Pazdur R, Ditsch N, Rastogi P, Eiermann W, von Minckwitz G. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014 Jul 12;384(9938):164-72. doi: 10.1016/S0140-6736(13)62422-8. Epub 2014 Feb 14.

  PMID: 24529560 BACKGROUND

• Semiglazov VF, Semiglazov VV, Dashyan GA, Ziltsova EK, Ivanov VG, Bozhok AA, Melnikova OA, Paltuev RM, Kletzel A, Berstein LM. Phase 2 randomized trial of primary endocrine therapy versus chemotherapy in postmenopausal patients with estrogen receptor-positive breast cancer. Cancer. 2007 Jul 15;110(2):244-54. doi: 10.1002/cncr.22789.

  PMID: 17538978 BACKGROUND

• Ellis MJ, Suman VJ, Hoog J, Lin L, Snider J, Prat A, Parker JS, Luo J, DeSchryver K, Allred DC, Esserman LJ, Unzeitig GW, Margenthaler J, Babiera GV, Marcom PK, Guenther JM, Watson MA, Leitch M, Hunt K, Olson JA. Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2 to 3 breast cancer: clinical and biomarker outcomes and predictive value of the baseline PAM50-based intrinsic subtype--ACOSOG Z1031. J Clin Oncol. 2011 Jun 10;29(17):2342-9. doi: 10.1200/JCO.2010.31.6950. Epub 2011 May 9.

  PMID: 21555689 BACKGROUND

• Masuda N, Sagara Y, Kinoshita T, Iwata H, Nakamura S, Yanagita Y, Nishimura R, Iwase H, Kamigaki S, Takei H, Noguchi S. Neoadjuvant anastrozole versus tamoxifen in patients receiving goserelin for premenopausal breast cancer (STAGE): a double-blind, randomised phase 3 trial. Lancet Oncol. 2012 Apr;13(4):345-52. doi: 10.1016/S1470-2045(11)70373-4. Epub 2012 Jan 20.

  PMID: 22265697 BACKGROUND

• Pagani O, Regan MM, Walley BA, Fleming GF, Colleoni M, Lang I, Gomez HL, Tondini C, Burstein HJ, Perez EA, Ciruelos E, Stearns V, Bonnefoi HR, Martino S, Geyer CE Jr, Pinotti G, Puglisi F, Crivellari D, Ruhstaller T, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Bernhard J, Luo W, Ribi K, Viale G, Coates AS, Gelber RD, Goldhirsch A, Francis PA; TEXT and SOFT Investigators; International Breast Cancer Study Group. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med. 2014 Jul 10;371(2):107-18. doi: 10.1056/NEJMoa1404037. Epub 2014 Jun 1.

  PMID: 24881463 BACKGROUND

• Francis PA, Regan MM, Fleming GF, Lang I, Ciruelos E, Bellet M, Bonnefoi HR, Climent MA, Da Prada GA, Burstein HJ, Martino S, Davidson NE, Geyer CE Jr, Walley BA, Coleman R, Kerbrat P, Buchholz S, Ingle JN, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Colleoni M, Viale G, Coates AS, Goldhirsch A, Gelber RD; SOFT Investigators; International Breast Cancer Study Group. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med. 2015 Jan 29;372(5):436-46. doi: 10.1056/NEJMoa1412379. Epub 2014 Dec 11.

  PMID: 25495490 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Goserelin; Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Combined Modality Therapy; Therapeutics

Study Officials

• Li Zhu, Prof

  Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 17, 2015
• First Posted: August 25, 2015
• Study Start: March 1, 2016
• Primary Completion: March 1, 2019
• Study Completion: March 1, 2019
• Last Updated: March 11, 2020

Record last verified: 2020-03

Locations

CN (1)