Clinical trial NCT02914158: Adjuvant Ovarian Suppression Plus Aromatase Inhibitor or Tamoxifen in Young Women
Official title: Adjuvant Ovarian Suppression Plus Aromatase Inhibitor or Tamoxifen for Hormone Receptor-Positive Breast Cancer in Women Younger Than 35: A Multicenter Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Breast Cancer
Keywords: breast cancer
ovarian function suppression (OFS)
aromatase inhibitors（AIs）
tamoxifen（TAM）
Lead sponsor: First Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2016-09-26
Enrollment: 680
Sex: FEMALE
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to compare the curative effects in patients under the age of 35 with hormone receptor positive breast cancer and high recurrent risk factors including large tumor or metastatic lymph nodes randomized to ovarian function suppression (OFS) plus aromatase inhibitors or OFS plus tamoxifen as adjuvant endocrine therapy, and explore the differences of curative effects between different subtypes to provide direct evidence for treatments of young breast cancer patients.


Eligibility criteria: Inclusion Criteria:

1. Signed informed consent;
2. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;
3. Patients pathologically diagnosed with hormone receptor positive invasive breast cancer: immunohistochemistry ER positive (≥1%);
4. Premenopausal patients with age ≤35 years (at least menstruate once for prior 3 months, assess menstruation situation before chemotherapy if have);
5. No distant metastasis;
6. Clinical stage (TNM) meets at least one of the conditions as follow: T≥2cm or at least one region of regional lymph node metastasis (including micrometastases);
7. Patients must have undergone a surgery and (neo)adjuvant chemotherapy, targeted therapy, radiotherapy (if necessary) according to Chinese Anti-Cancer Association guidelines and specifications version 2015 for diagnosis and treatment of breast cancer;
8. Indexes of hematology and biochemistry conform to following standards: HGB≥10g/dl, WBC≥4,000/mm3, PLT≥100,000/mm3, GOT, GPT, ALP≤2xULN, TBIL, DBIL, CCr≤1.5xULN.

Exclusion Criteria:

1. Pregnant or lactating women or women of childbearing potential reject contraceptive measures;
2. History of organ transplantation (including autologous bone marrow transplantation and peripheral stem cell transplantation);
3. Concurrent malignancies or history of non-breast malignancies within the 5 years prior to study entry, except for curatively treated basal cell and squamous cell carcinomas of the skin, carcinoma in situ of the cervix; peripheral nervous system disorders caused by diseases or history of obvious mental and central nervous system disorders;
4. Prior use of neo-adjuvant chemotherapy after a definite diagnosis;
5. Nervous system disorders caused by diseases or obvious mental disorder, which would affect patients right to consent and compliance, or make patients in critical condition;
6. Serious hepatopathy (e.g., cirrhosis, etc.), nephropathy, respiratory illness, digestive illness or poorly controlled diabetes;
7. Cardiac illness with obvious abnormal EKG or clinical symptoms, namely congestive heart failure, coronary atherosclerotic heart disease with obvious symptoms, arrhythmia difficult to control by drugs, or history of myocardial infarction within the 12 months prior to study entry or class III/IV of cardiac function;
8. Concurrent treatment in another investigational trial;
9. Sensitivity or contraindication to any of the study medications.

Primary outcomes:
measure: Disease-Free Survival (DFS)
timeFrame: 5 years
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 5 years
measure: Invasive Breast Cancer Recurrence-Free Interval（BCFI)
timeFrame: 5 years
measure: Adverse Effects Rate
timeFrame: 5 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
city: Beijing
country: China
facility: Peking University First Hospital
city: Dongguan
country: China
facility: Dongguan People's Hospital
city: Guangzhou
country: China
facility: GuangDong Hospital Of Traditional Chinese Medicine
city: Guangzhou
country: China
facility: Guangdong People's Hospital
city: Guangzhou
country: China
facility: Guangdong Provincial Women and Children's Hospital
city: Guangzhou
country: China
facility: Guangzhou First Municipal People's Hospital
city: Guangzhou
country: China
facility: Guangzhou Women and Childrens Medical Center
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital, Sun Yat-sen University
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
city: Guangzhou
country: China
facility: The Second Affiliated Hospital of Guangzhou Medical University
city: Guilin
country: China
facility: Guilin TCMhospital of China
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Kunming
country: China
facility: Yunnan Cancer Hospital
city: Maoming
country: China
facility: Maoming People's Hospital
city: Nanning
country: China
facility: The first Affiliated Hospital of Guangxi Medical University
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
city: Zhanjiang
country: China
facility: Affiliated hospital of Guangdong Medicine College
city: Zhanjiang
country: China
facility: Affiliated hospital of Guangdong Medicine College
city: Zhanjiang
country: China
facility: Lian Jiang People' s Hospital
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
city: Zhongshan
country: China
facility: Zhongshan People's Hospital
city: Zhuhai
country: China
facility: The Fifth Affiliated Hospital Sun Yat-Sen University
Study officials:
References:
citation: Fan L, Strasser-Weippl K, Li JJ, St Louis J, Finkelstein DM, Yu KD, Chen WQ, Shao ZM, Goss PE. Breast cancer in China. Lancet Oncol. 2014 Jun;15(7):e279-89. doi: 10.1016/S1470-2045(13)70567-9.
citation: Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet. 2015 Oct 3;386(10001):1341-1352. doi: 10.1016/S0140-6736(15)61074-1. Epub 2015 Jul 23.
citation: LHRH-agonists in Early Breast Cancer Overview group; Cuzick J, Ambroisine L, Davidson N, Jakesz R, Kaufmann M, Regan M, Sainsbury R. Use of luteinising-hormone-releasing hormone agonists as adjuvant treatment in premenopausal patients with hormone-receptor-positive breast cancer: a meta-analysis of individual patient data from randomised adjuvant trials. Lancet. 2007 May 19;369(9574):1711-23. doi: 10.1016/S0140-6736(07)60778-8.
citation: 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.
citation: 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.