Clinical trial NCT03085368: A Randomized Controlled Trial of HER-2 Positive Breast Cancer Patients Treated With Lapatinib vs Herceptin
Official title: A Randomized Controlled Trial of HER-2 Positive Breast Cancer Patients Treated With Lapatinib and Paclitaxel vs Herceptin and Paclitaxel With Sequential and Synchronous Anthracycline
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: HER2-positive Breast Cancer
Keywords: breast cancer
her-2 positive
lapatinib
herceptin
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: Taizhou EOC Pharma Co., Ltd.
First posted: 2017-03-21
Enrollment: 482
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized controlled trial of HER-2 positive breast cancer patients treated with lapatinib and paclitaxel vs herceptin and paclitaxel with sequential and synchronous anthracycline

Detailed description: This is a randomized controlled trial of HER-2 positive breast cancer patients treated with lapatinib and paclitaxel vs herceptin and paclitaxel with sequential and synchronous anthracycline. Safety and efficacy are the primary endpoint. The positive expression of HER2 was confirmed by postoperative pathology in patients with breast adenocarcinoma (IDC). Patients who had not received any chemotherapy and targeted anti HER2 therapy.

In this study, the non inferiority design method, according to the wishes of patients and signed informed consent, randomly into the group, a total of 482 patients were enrolled in the trial group: the control group =1:1. The subjects were followed up for a total of 1 years, until the disease progressed, and the toxicity was not tolerated.

We want to study 84 months. The follow-up period was 5 years (the first adjuvant treatment time to the last follow-up) or the researchers decided to end the study.

Eligibility criteria: Inclusion Criteria:

1. the first diagnosis of invasive breast cancer, confirmed by histology or cytology, and surgical resection of the primary lesions before receiving any anti breast cancer treatment;
2. female patients, aged 18 years and less than 80 years of age;
3. surgical resection of the primary tumor pathological examination, showed HER2 positive (defined as immunohistochemistry \[IHC\] 3+ or fluorescence in situ hybridization (FISH) positive);
4. hormone receptor status is known, lymph node positive or sentinel lymph node negative but high risk factors
5. the eastern oncology cooperative group (ECOG) patients with physical status score was 0 -2;
6. baseline LVEF \>50%
7. the relevant institutional review board (IRB) or independent ethics committee (IEC) written informed consent

Exclusion Criteria:

1. the subjects in pregnancy or lactation;
2. pregnant women may be within the first 7 days before pregnancy test positive (urine or serum).
3. received chemotherapy, endocrine or anti HER2 anti-tumor therapy;
4. congestive heart failure, unstable angina, heart failure or myocardial infarction and other diseases;
5. other invasive tumors (including the second primary breast cancer), may affect the outcome of the evaluation and program compliance; but the treatment of patients with disease free survival at least more than 5 years can be selected;
6. with chronic liver disease in patients with liver dysfunction and / or with clinical manifestations: the serum total bilirubin \> 2.5 \* ULN; or INR = 1.5 but no bilirubin. serum ALT or AST\> \* 3 \* ULN; alkaline phosphatase \>2.5 \* ULN; ALT or AST can be gradually increased, but with gradually increasing fatigue, nausea and vomiting, fever, right upper quadrant pain or tenderness
7. hematopoietic dysfunction, defined as follows: neutrophil count (ANC) \<1.5 \* 109/L; platelet \<100 \* 109/L; hemoglobin \<9 g/dL;
8. other serious diseases, including: congestive heart failure (heart function NYHA grade II, III, IV) or occurred within 6 months of congestive heart failure, unstable angina, arrhythmia, myocardial infarction patients can't control or other severe cardiovascular disease; breathing at rest or need oxygen therapy; serious infection; uncontrolled diabetes;
9. there is a serious psychological or mental abnormalities, estimated that the participants to participate in this study is not strong;
10. known to study drug allergy;
11. the past 30 days participated in the study of other drug clinical trials.

1, failed to complete the clinical trial of at least 1 cycles according to the program, can not carry out safety and efficacy evaluation 2, a serious violation of this research program, not in accordance with the prescribed dose, method and course of medication.

Patients will receive lapatinib treatment, until a predetermined end end point, or development of unacceptable toxicity, or withdrawal of consent, or illness or death, to appear before the subject.

Primary outcomes:
measure: DFS
timeFrame: 3 years& 5 years
Secondary outcomes:
measure: OS
timeFrame: 5 years & 10 years
Other outcomes:
measure: biomarker
timeFrame: 5 years
Locations:
city: Beijing
country: China
facility: PUMCH
Study officials:
affiliation: PUMCH
name: Sun Qiang, M.D.
role: STUDY_CHAIR
References:
citation: Piccart-Gebhart M, Holmes E, Baselga J, de Azambuja E, Dueck AC, Viale G, Zujewski JA, Goldhirsch A, Armour A, Pritchard KI, McCullough AE, Dolci S, McFadden E, Holmes AP, Tonghua L, Eidtmann H, Dinh P, Di Cosimo S, Harbeck N, Tjulandin S, Im YH, Huang CS, Dieras V, Hillman DW, Wolff AC, Jackisch C, Lang I, Untch M, Smith I, Boyle F, Xu B, Gomez H, Suter T, Gelber RD, Perez EA. Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial. J Clin Oncol. 2016 Apr 1;34(10):1034-42. doi: 10.1200/JCO.2015.62.1797. Epub 2015 Nov 23.
citation: Goss PE, Smith IE, O'Shaughnessy J, Ejlertsen B, Kaufmann M, Boyle F, Buzdar AU, Fumoleau P, Gradishar W, Martin M, Moy B, Piccart-Gebhart M, Pritchard KI, Lindquist D, Chavarri-Guerra Y, Aktan G, Rappold E, Williams LS, Finkelstein DM; TEACH investigators. Adjuvant lapatinib for women with early-stage HER2-positive breast cancer: a randomised, controlled, phase 3 trial. Lancet Oncol. 2013 Jan;14(1):88-96. doi: 10.1016/S1470-2045(12)70508-9. Epub 2012 Dec 10.