A clinical study to evaluate the safety and efficacy of Endoxifen in metastatic breast cancer patients

Phase 1

Completed

Conditions: Malignant neoplasm of breast of unspecified site,

Registration Number: CTRI/2010/091/002918

Lead Sponsor: Intas Pharmaceuticals Ltd

Brief Summary: This is an Open Label, Multiple Dose Escalating Cohort Study To Evaluate Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Orally Administered Endoxifen In Metastatic Breast Cancer Patients. There are 4 cohorts in the study Cohort 1: 2mg tablet of endoxifen once daily for 28 days Cohort 2: 4mg (2 x 2mg) tablet of endoxifen once daily for 28 days Cohort 3: 8mg (4 x 2mg) tablet of endoxifen once daily for 28 days Cohort 0: 1mg tablet of endoxifen once daily for 28 days Cohort 1 will receive 2 mg of Endoxifen once daily for 28 days and if found safe, Cohort 2 will receive 4 mg of Endoxifen once daily for 28 days. If 4 mg dose is found safe, then Cohort 3 will receive 8 mg of Endoxifen. If the Cohort 1 shows toxicity, then Cohort 0 will be administered 1 mg of Endoxifen Rationale for Dose selection Long-term systemic exposures to high levels of Endoxifen are found to be safe in women receiving Tamoxifen therapy. Breast cancer patients have variable capability to metabolize Tamoxifen due to variable function of enzyme cytochrome P450 2D6 (CYP2D6). Studies have shown a clear correlation of specific genetic variant of CYP2D6 with Endoxifen blood levels. The genetic polymorphisms of CYP2D6 have effects on steady-state plasma concentration of Endoxifen in patients receiving Tamoxifen therapy. Recent clinical investigations have shown the correlation with genetic variant of CYP2D6 and breast cancer relapse in early breast cancer patients treated with Tamoxifen. The higher systemic exposure to Endoxifen results in higher clinical efficacy measured as recurrence-free survival Primary objective: To evaluate safety, tolerability and steady state Pharmacokinetics of Endoxifen at escalating multiple-dose administered for 28 days in metastatic breast cancer patients. Secondary Objective: To evaluate Pharmacodynamics of Endoxifen administered for 28 days in metastatic breast cancer patients. Assessment of Pharmacodynamics includes improvement in Ki-67 (cancer proliferation marker) in breast cancer tissue; and serum estradiol, estrone, and estrone sulfate levels. NUMBER OF PATIENTS: Maximum 18 Patients will be enrolled from India. Each Cohort will have 6 patients

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Female

Target Recruitment: 18

Inclusion Criteria

The patient willing to give written informed consent to participate in the study before initiating any study related procedures.
Female more than 18 years of age on the day of signing the ICD 3.
Patient with histologically or cytologically confirmed breast cancer before signing of ICD 4.
Patients must have confirmation of inoperable metastatic breast cancer before signing of ICD 5.
The patients should be eligible for third line therapy with resistance to Tamoxifen or Aromatase Inhibitors.
Pt must have negative serum pregnancy test at screening (need not to be performed for postmenopausal women).

Exclusion Criteria

1.Patient with known history of drug addiction within last 1 year.
2.Patients with known CNS lesions (brain metastasis or carcinomatous meningitis).
3.Patient with history of Thromboembolism or stroke.
4.Known case of HIV infection.
5.Patient with history of ocular disturbances including corneal changes, decrement in color vision perception, retinal vein thrombosis, cataract and retinopathy.
6.Patient with history of endometrial adenocarcinoma, uterine sarcoma or known history of abnormal vaginal bleeding.
7.Abnormal baseline findings considered by the investigator to indicate conditions that might affect study endpoints.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To evaluate safety, tolerability and steady state Pharmacokinetics (PK) of Endoxifen at escalating multiple-dose administered for 28 days in metastatic breast cancer patients	28 days

Secondary Outcome Measures

Name	Time	Method
To evaluate Pharmacodynamics (PD) of	Endoxifen administered for 28 days in metastatic breast cancer patients. Assessment of PD includes improvement in serum estradiol,estrone, and estrone sulfate levels.

Trial Locations

Locations (5): Dr. Rai Memorial medical Centre
🇮🇳
Chennai, TAMIL NADU, India
Kasturba Medical College and Hospital
🇮🇳
Bangalore, KARNATAKA, India
Lions Cancer Detection Centre
🇮🇳
Surat, GUJARAT, India
Mahavir cancer sansthan
🇮🇳
Patna, BIHAR, India
Manavata Curie Cancer Center
🇮🇳
Nashik, MAHARASHTRA, India
Dr. Rai Memorial medical Centre
🇮🇳Chennai, TAMIL NADU, India
DrKrishnan
Principal investigator
09952933735
krishnan_dr@yahoo.com