A Phase Ib Study to Assess Safety and Efficacy of Oral Icaritin in Advanced Solid Tumors

NCT ID: NCT02496949

Last Updated: 2015-07-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2013-08-31

Brief Summary

to assess the safety, tolerability，PK and efficacy profile of two doses (600mg,800mg,BID) of Icaritin in advanced solid tumor patients in China

Detailed Description

Estrogen receptor,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 the mitogen-activated protein kinase/extracellular signal-regulated kinases (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 molecule with selective ERa36 modulating capability and the potential as a very promising new drug to treat advanced breast cancer and hepatocellular carcinoma (HCC) by targeting this nongenomic pathway. Studies showed that it can inhibit the growth of cancer cells both in vitro and in vivo. The investigators have completed the preclinical pharmacokinetic, pharmacodynamic (PK&PD) and toxicity studies in animals and now move on to test it in a phase Ib clinical trial.

Conditions

Solid Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Icaritin

600mg,800mg two doses, Bid, continuous dosing for 56 days, to assess the safety,tolerance,pharmacokinetics and efficacy of icaritin

Group Type: EXPERIMENTAL

Icaritin

Intervention Type: DRUG

600mg,800mg two doses, Bid, continuous dosing for 56 days, to assess the safety,tolerance,pharmacokinetics and efficacy of icaritin

Interventions

Icaritin

600mg,800mg two doses, Bid, continuous dosing for 56 days, to assess the safety,tolerance,pharmacokinetics and efficacy of icaritin

Intervention Type: DRUG

Other Intervention Names

IC-162

Eligibility Criteria

Inclusion Criteria

1. age≥18 years old and ≤65

2. The patients with advanced breast tumors，hepatocellular carcinoma (HCC) or other advanced solid tumor patients who are confirmed through histologic or cytologic diagnosis to be ER positive or subjects whom investigators believe may benefit from the trial.

3. Patients with advanced cancer that relapsed after or failed previous standard treatment

4. 19≤BMI index≤30

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

6. .Received at least one anti-cancer treatment (including chemotherapy, radiotherapy, biological or endocrine treatment). And the last treatment must be at least four weeks before study enrollment or after 5 times of the drug's half-life time has passed. The surgery treatment must be more than three months.

7. Life expectancy of at least 12 weeks. 8 .Patients who 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. The Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 12. Female:Women with childbearing potential must have a negative pregnancy test performed 13. HCC patients: Child-Pugh Class of A or B

Exclusion Criteria

1. Have a known hypersensitivity to flavonoid drugs.

2. Hepatic:

1. HCC patients : ALB <2.8g/dL, TB>3.0mg/dL, ALT and AST > 2.5 times the upper limit of Normal

2. Advanced breast tumors or other advanced solid tumor patients: ALB >limit of 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. Blood test: 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. HCC patients: PT > 5 seconds above control

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. Malabsorption or other disease which will affect the drug absorption,distribution,metabolism and excretion.

10. Other concurrent malignancies with the exception of cervical cancer in situ or squamous cell carcinoma of the skin .

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing Shenogen Biomedical Co., Ltd

INDUSTRY

Sponsor Role: collaborator

Chinese Academy of Medical Sciences

OTHER

Sponsor Role: lead

Responsible Party

Binghe Xu

Internal medicine director,Cancer institute & hospital

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bing he Xu, MD

Role: PRINCIPAL_INVESTIGATOR

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Locations

Cancer institute & hospital, chinese academy of medical sciences

Beijing, Beijing Municipality, China

Countries

China

References

Fan Y, Li S, Ding X, Yue J, Jiang J, Zhao H, Hao R, Qiu W, Liu K, Li Y, Wang S, Zheng L, Ye B, Meng K, Xu B. First-in-class immune-modulating small molecule Icaritin in advanced hepatocellular carcinoma: preliminary results of safety, durable survival and immune biomarkers. BMC Cancer. 2019 Mar 28;19(1):279. doi: 10.1186/s12885-019-5471-1.

Reference Type: DERIVED

PMID: 30922248 (View on PubMed)

Other Identifiers

TG1114ICR

Identifier Type: -

Identifier Source: org_study_id