Clinical trial NCT03045653
Conditions: Breast Cancer Metastatic
Keywords: Breast Cancer high dose Tamoxifen endocrine therapy Hormone Receptor Positive Malignant Neoplasm of Breast Tamoxifen Breast Cancer Metastatic
Sponsor: Sun Yat-sen University
Start date: 2017-09-01; Completion date: 2019-02-21
Enrollment: 30 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Background: Endocrine therapy is an effective and safe treatment for hormone receptor positive breast cancer. Unfortunately , endocrine treatment resistance occurs and there is an urgent need for treatment alternative. Laboratory researches and clinical case reports indicate that hormone receptor-high expressed breast cancer patients may potentially benefit from high-dose Tamoxifen or high-dose Tamoxifen plus chemotherapy , providing a new option for treatment strategy.

Aim: To explore the efficacy and safety of high-dose Tamoxifen to standard hormone receptor-high expressed endocrine therapy resisted breast cancer.

Methods: Eligible patients will be treated with tamoxifen 100 mg/d or high-dose Tamoxifen(100 mg/d ) plus chemotherapy. Blood and tumor samples will be obtained from the patients.Evaluate curative effect every 3 months.

Primary endpoint: progression-free survival (PFS). Secondary endpoints: objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS) and safety.

Exploratory endpointsincluded the efficacy predictive value of the 18F-FES SUVmax.

Detailed description:

Arms: arm 1: receiving a treatment of tamoxifen 100 mg/d or high-dose Tamoxifen(100 mg/d ) plus chemotherapy
Interventions: intervention 1: Tamoxifen Oral Product
Intervention descriptions: intervention 1: Tamoxifen 100 mg/d or high-dose Tamoxifen(100 mg/d ) plus chemotherapy

Protocol documents:
Prot_SAP_000.pdf: 
Efficacy and Safety of High Dose Tamoxifen to Advanced Hormone Receptor-
High Expressed Endocrine Therapy Resisted Breast Cancer: A Single-arm Phase 
II Pilot Trial 
 
NCT number: NCT03045653 
Study Institution: Sun Yat-Sen University Cancer Center, State Key Laboratory of 
Oncology in South China, Collaborative innovation center for Cancer Medicine 
Protocol Version: v 2.0 
Date: 2018-01-10 
 
Protocol Synopsis: This study conducted a single arm open label phase 2 trail. Patients 
received treatments of 100 mg/d tamoxifen. The primary endpoint was the progression-
free survival (PFS). Secondary endpoints included objective response rate (ORR), 
clinical benefit rate (CBR), overall survival (OS) and safety. Exploratory endpoints 
included the efficacy predictive value of the 18F-FES SUVmax. 
 
Inclusion Criteria: 
Eligible patients were 18-70 years old females with pathologically or histologically 
confirmed MBC and high expression of ER or progesterone receptor in metastatic or 
primary tumor lesions (immunohistochemical staining: ER-positive cells ≥ 60% 
and/or progesterone receptor-positive cells ≥ 60%). Patients had disease that 
progressed ≥ 12 months after adjuvant endocrine treatment or after receiving 
standard endocrine salvage treatment. Patients had an Eastern Cooperative Oncology 
Group performance status of 0 or 1. MBC had to be measurable by Response Evaluation 
Criteria in Solid Tumors (RECIST) version 1.1 or had to be immeasurable bone-only 
disease. For patients who planned to undergo baseline 18F-FES PET/CT examination, 
discontinuation of TAM for ≥ 2 months was required to avoid the blockade of the 
imaging agent. 


Exclusion Criteria: 
The exclusion criteria included primary ET resistance (disease relapsed within the first 
2 years of neoadjuvant or adjuvant ET or progressed within the first 6 months of ET for 
MBC); visceral crisis; evidence or history of central nervous system metastasis. 
 
Interventions 
After enrollment and the signing of informed consent, patients received oral 100 mg/d 
TAM treatment until disease progression. 
 
Study Endpoints: 
The primary endpoint was progression-free survival (PFS). The key secondary 
endpoints included ORR (the proportion of patients with complete response [CR] or 
partial response [PR] per RECIST version 1.1), CBR (the proportion of patients with 
CR, PR or stable disease [SD] ≥ 6 months), overall survival (OS), safety and 
tolerability. The exploratory endpoints included the predictive value of the 18F-FES 
maximum standardized uptake value (SUVmax) of 18F-FES PET/CT on the efficacy 
of high-dose TAM therapy. 
 
Response evaluation criteria for a single lesion: referring to the RECIST 1.1 standard, 
we defined the response evaluation criteria for a single lesion. Progressive disease (PD): 
the maximum diameter of a single metastasis lesion increased by more than 20%; CR: 
disappearance of target lesions; PR: the maximum diameter of the lesion decreased by 
more than 30%; the rest were considered SD. The definition of clinical benefit of a 
single lesion: according to the response evaluation criteria for a single lesion, CR, PR, 
or SD ≥ 6 months was defined as clinical benefit of a single lesion. 
 


Statistical Analysis 
The primary endpoint of PFS was determined based on an intention-to-treat set. If no 
PFS event was observed before the cutoff date, the last tumor assessment date was 
defined as censored. Safety was analyzed based on a safety analysis set defined as all 
patients who received at least one dose of high-dose TAM and had at least one 
posttreatment safety assessment. Median PFS was estimated with the Kaplan-Meier 
method and compared by log-rank tests. The comparison of continuous variables 
between two samples of normal distribution was performed by the t-test, and the 
comparison of the two categorical data was conducted with the Chi-square test. 
For all analyses, a 2-tailed p ≤ 0.05 was considered statistically significant, and all 
confidence intervals used a 95% confidence level. Statistical analyses were performed 
by the investigators at the Cancer Center of Sun Yat-sen University using SPSS 
software version 20.0 (SPSS Inc.) and SAS version 9.4 (SAS Institute).