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A Phase I ,Single Center, Open-labeling, Single and Dose-escalating Study to Assess the Safety, Tolerability and Pharmacokinetic Profile of Oral Novel ERa36 Modifier Icaritin in Advanced Breast Patients

Phase 1
18 Years
65 Years
Open (Enrolling)
Metastatic Breast Cancer

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Trial Information

A Phase I ,Single Center, Open-labeling, Single and Dose-escalating Study to Assess the Safety, Tolerability and Pharmacokinetic Profile of Oral Novel ERa36 Modifier Icaritin in Advanced Breast Patients

ERa36 predominantly localizes on the plasma membrane and in the cytoplasm and mediates a
membrane-initiated "nongenomic" signaling pathway. Membrane-initiated estrogen signaling has
been linked to rapid responses to estrogen and generally activates signaling pathways like
MAPK/ERK, phosphatidylinositol-3-kinase, and protein kinase C pathways. Preclinical study
demonstrated that ERa36 was expressed in tumor cells and might be the driving force of
breast cancer cell proliferation. 40% of breast cancer tumors which used to be considered as
ER negative also express ERa36. In the former study the investigators found that 40% of
ERa66-positive breast cancer patients express high levels of ERa36 in their tumors, and this
subset of patients are less likely to benefit from tamoxifen treatment compared with those
with ERa66-positive/ERa36-negative tumors.

Icaritin is a newly discovered small molecular compound which is high selective ERa36
modulators and perhaps will be a very promising new drug to treat advanced breast cancer by
targeting this nongenomic pathway. It was showed that it can inhibit the growth of breast
cancer cells both in vitro and in vivo. The investigators have completed the preclinical
PK&PD and toxicity studies in animals and now move on to test it in a FIM clinical trial.

Inclusion Criteria:

1. Female, age ≥ 18 years old and ≤ 65 years old

2. The patients with advanced breast tumors who are confirmed through histologic or
cytologic diagnosis with ER positive or investigator think that subjects will benefit
from the trial

3. The advanced breast cancer patients which relapse or failure from previous standard

4. 19 ≤ BMI index ≤ 30

5. No serious heart, liver,lung and kidney diseases

6. Received at least once anti-cancer treatment (including chemotherapy, radiotherapy,
biological or endocrine treatment). And the last treatment must be at least four
weeks before study enrollment or more than 5 times half life. The surgery treatment
must be more than three months

7. Life expectancy of at least 12 weeks

8. Patients which can cooperate to observe AE and efficacy

9. No any other concurrent anti-cancer treatment

10. A signed informed consent must be obtained prior to performing any study specific

11. ECOG Performance Status of 0,1

12. Female:Women with childbearing potential must have a negative pregnancy test

Exclusion Criteria:

1. Have a known hypersensitivity to flavonoid drugs

2. Hepatic:

- ALB >limit if normal

- TB> the upper limit of normal

- ALT and AST > upper limit of Normal


- Serum Creatinine > 1.5 times the upper limit of normal

Bone marrow:

- Absolute neutrophil count (ANC) < 1.5 × 109/L

- Platelet count < 90 × 109/L

- Hemoglobin < 9 g/dL

3. PT/APTT > 1.25 times the upper limit of normal

4. Suffered from thrombotic disease

5. Serum Ca > the upper limit of normal

6. Not recovered from toxic effects of previous anti-cancer treatments or surgery

7. Any serious or uncontrollable concomitant systemic disorder (such as unstable
respiratory disorders, cardiovascular, hepatic or kidney disorders.) or active
infection which will influence the clinical trial

8. CNS metastases or invade requiring treatment for unstable status or various
psychiatric disorders

9. No malabsorption or other disease which will affect the drug
absorption,distribution,metabolism and excretion

10. Concurrent other malignancies with the exception of cervical cancer in situ or
squamous Cell Carcinoma of the Skin

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To assess safety of icaritin in breast cancer patients

Outcome Description:

to find the dose-limiting toxicity(DLT)and maximal tolerated dose(MTD)of icaritin in breast cancer patients

Outcome Time Frame:

1-2 YEAR

Safety Issue:


Principal Investigator

Binghe Xu, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cancer Institute Hospital, Chinese Academy of Medical Sciences


China: Food and Drug Administration

Study ID:




Start Date:

November 2010

Completion Date:

December 2011

Related Keywords:

  • Metastatic Breast Cancer
  • Icaritin,
  • ERa36
  • Breast Neoplasms