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Phase I Study of Novel Estrogen Receptor(ER) a36 Modifier Icaritin in Advanced Breast Cancer Patients

Primary Purpose

Metastatic Breast Cancer

Status

Unknown status

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

Icaritin

About this trial

This is an interventional treatment trial for Metastatic Breast Cancer focused on measuring Icaritin,, ERa36

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

Female, age ≥ 18 years old and ≤ 65 years old
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
The advanced breast cancer patients which relapse or failure from previous standard treatment
19 ≤ BMI index ≤ 30
No serious heart, liver,lung and kidney diseases
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
Life expectancy of at least 12 weeks
Patients which can cooperate to observe AE and efficacy
No any other concurrent anti-cancer treatment
A signed informed consent must be obtained prior to performing any study specific procedures
ECOG Performance Status of 0,1
Female:Women with childbearing potential must have a negative pregnancy test performed

Exclusion Criteria:

Have a known hypersensitivity to flavonoid drugs
Hepatic:
- ALB >limit if normal
- TB> the upper limit of normal
- ALT and AST > upper limit of Normal
Renal:
- 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
PT/APTT > 1.25 times the upper limit of normal
Suffered from thrombotic disease
Serum Ca > the upper limit of normal
Not recovered from toxic effects of previous anti-cancer treatments or surgery
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
CNS metastases or invade requiring treatment for unstable status or various psychiatric disorders
No malabsorption or other disease which will affect the drug absorption,distribution,metabolism and excretion
Concurrent other malignancies with the exception of cervical cancer in situ or squamous Cell Carcinoma of the Skin

Sites / Locations

Cancer institute & hospital, chinese academy of medical sciencesRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Icaritin

Arm Description

Outcomes

Primary Outcome Measures

To assess safety of icaritin in breast cancer patients

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

Secondary Outcome Measures

To assess pharmacokinetic profile of icaritin in breast cancer patients

Full Information

NCT ID

NCT01278810

First Posted

January 18, 2011

Last Updated

January 27, 2011

Sponsor

Chinese Academy of Medical Sciences

Collaborators

Beijing Shenogen Biomedical Co., Ltd

1. Study Identification

Unique Protocol Identification Number

NCT01278810

Brief Title

Phase I Study of Novel Estrogen Receptor(ER) a36 Modifier Icaritin in Advanced Breast Cancer Patients

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2010

Overall Recruitment Status

Unknown status

Study Start Date

November 2010 (undefined)

Primary Completion Date

November 2011 (Anticipated)

Study Completion Date

December 2011 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor

Chinese Academy of Medical Sciences

Collaborators

Beijing Shenogen Biomedical Co., Ltd

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

To assess safety, tolerance and PK profile of different doses(50mg,100mg,200mg,300mg, 400mg, 500mg,QD)of Icaritin in advanced breast cancer Patients in China

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastatic Breast Cancer

Keywords

Icaritin,, ERa36

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Icaritin

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Icaritin

Other Intervention Name(s)

IC-162

Intervention Description

50mg,100mg,200mg,300mg,400mg,500mg ascending-multiple oral dose, Qd, single dose and continuing dose 28 days, to assess the safety,tolerance and pharmacokinetics of icaritin

Primary Outcome Measure Information:

Title

To assess safety of icaritin in breast cancer patients

Description

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

Time Frame

1-2 YEAR

Secondary Outcome Measure Information:

Title

To assess pharmacokinetic profile of icaritin in breast cancer patients

Time Frame

1 year

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Female, age ≥ 18 years old and ≤ 65 years old 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 The advanced breast cancer patients which relapse or failure from previous standard treatment 19 ≤ BMI index ≤ 30 No serious heart, liver,lung and kidney diseases 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 Life expectancy of at least 12 weeks Patients which can cooperate to observe AE and efficacy No any other concurrent anti-cancer treatment A signed informed consent must be obtained prior to performing any study specific procedures ECOG Performance Status of 0,1 Female:Women with childbearing potential must have a negative pregnancy test performed Exclusion Criteria: Have a known hypersensitivity to flavonoid drugs Hepatic: ALB >limit if normal TB> the upper limit of normal ALT and AST > upper limit of Normal Renal: 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 PT/APTT > 1.25 times the upper limit of normal Suffered from thrombotic disease Serum Ca > the upper limit of normal Not recovered from toxic effects of previous anti-cancer treatments or surgery 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 CNS metastases or invade requiring treatment for unstable status or various psychiatric disorders No malabsorption or other disease which will affect the drug absorption,distribution,metabolism and excretion Concurrent other malignancies with the exception of cervical cancer in situ or squamous Cell Carcinoma of the Skin

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Binghe Xu, MD

Organizational Affiliation

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Binghe Xu, MD

Organizational Affiliation

Cancer institute & hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Cancer institute & hospital, chinese academy of medical sciences

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100021

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ying Fan, MD

Phone

+86 010-87788120

fanying@csco.org.cn

12. IPD Sharing Statement

Learn more about this trial

Phase I Study of Novel Estrogen Receptor(ER) a36 Modifier Icaritin in Advanced Breast Cancer Patients

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