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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2010 by Chinese Academy of Medical Sciences.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Beijing Shenogen Biomedical Co.,Ltd
Information provided by:
Chinese Academy of Medical Sciences
ClinicalTrials.gov Identifier:
NCT01278810
First received: January 18, 2011
Last updated: January 27, 2011
Last verified: November 2010
History of Changes
  Purpose

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


Condition Intervention Phase
Metastatic Breast Cancer
 Drug: Icaritin
 Phase 1

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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Chinese Academy of Medical Sciences:

Primary Outcome Measures:
  • To assess safety of icaritin in breast cancer patients [ Time Frame: 1-2 YEAR ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: November 2010
Estimated Study Completion Date: December 2011
Estimated Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Icaritin Drug: Icaritin
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
Other Name: IC-162

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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 treatment
  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 procedures
  11. ECOG Performance Status of 0,1
  12. Female:Women with childbearing potential must have a negative pregnancy test performed

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

    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
  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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01278810

Locations
China, Beijing
Cancer institute & hospital, chinese academy of medical sciences Recruiting
Beijing, Beijing, China, 100021
Contact: Ying Fan, MD     +86 010-87788120     fanying@csco.org.cn    
Sponsors and Collaborators
Chinese Academy of Medical Sciences
Beijing Shenogen Biomedical Co.,Ltd
Investigators
Principal Investigator: Binghe Xu, MD Cancer Institute Hospital, Chinese Academy of Medical Sciences
Principal Investigator: Binghe Xu, MD Cancer institute & hospital
  More Information

No publications provided

Responsible Party: xubinghe, Cancer institute & hospital, chinese academy of medical sciences
ClinicalTrials.gov Identifier: NCT01278810     History of Changes
Other Study ID Numbers: TG0929ICR
Study First Received: January 18, 2011
Last Updated: January 27, 2011
Health Authority: China: Food and Drug Administration

Keywords provided by Chinese Academy of Medical Sciences:
Icaritin,
ERa36

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on May 22, 2013