| CTRI Number |
CTRI/2010/091/002918 [Registered on: 21/10/2010] |
| Last Modified On: |
23/11/2018 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
Type of Study
Modification(s)
|
Drug |
| Study Design |
Single Arm Study |
Public Title of Study
Modification(s)
|
A clinical study to evaluate the safety and efficacy of Endoxifen in metastatic breast cancer patients |
Scientific Title of Study
Modification(s)
|
AN OPEN LABEL, MULTIPLE DOSE ESCALATING COHORT STUDY TO EVALUATE SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF ORALLY ADMINISTERED ENDOXIFEN IN METASTATIC BREAST CANCER PATIENTS |
| Trial Acronym |
NA |
Secondary IDs if Any
Modification(s)
|
| Secondary ID |
Identifier |
| 051-10 |
Protocol Number |
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)
|
| Name |
Rajesh CN |
| Designation |
Asst General Manager |
| Affiliation |
|
| Address |
Lambda Therapeutic Research Ltd.,
Near Gujarat High Court,
S.G. Highway, Gota,
Ahmadabad
GUJARAT
380061
India |
| Phone |
079-40202051 |
| Fax |
079-40202022 |
| Email |
rajeshcn@lambda-cro.com |
|
Details of Contact Person
Scientific Query
Modification(s)
|
| Name |
Dr Praveen Shetty |
| Designation |
|
| Affiliation |
NIL |
| Address |
Lambda Therapeutic Research Ltd.,
Near Gujarat High Court,S.G. Highway, Gota
Ahmadabad
GUJARAT
380061
India |
| Phone |
079-40202098 |
| Fax |
079-40202022 |
| Email |
praveenshetty@lambda-cro.com |
|
Details of Contact Person
Public Query
Modification(s)
|
| Name |
Rajesh CN |
| Designation |
|
| Affiliation |
|
| Address |
Lambda Therapeutic Research Ltd.,
Near Gujarat High Court,S.G. Highway, Gota
Ahmadabad
GUJARAT
380061
India |
| Phone |
079-40202051 |
| Fax |
079-40202022 |
| Email |
rajeshcn@lambda-cro.com |
|
Source of Monetary or Material Support
Modification(s)
|
| Intas Pharmaceuticals Ltd, 2nd Floor, Chinubhai Centre, Ashram Road, Ahmedabad 380-009, Gujarat, India, Tel. No.: + 91-79-2657-6655, Fax: + 91-79-2657-8862. |
|
Primary Sponsor
Modification(s)
|
| Name |
Intas Pharmaceuticals Ltd |
| Address |
Intas Pharmaceuticals Ltd, 2nd Floor,Chinubhai Centre, Ashram Road, Ahmedabad
380-009, Gujarat, India, |
| Type of Sponsor |
Pharmaceutical industry-Indian |
|
Details of Secondary Sponsor
Modification(s)
|
|
Countries of Recruitment
Modification(s)
|
India |
Sites of Study
Modification(s)
|
| No of Sites = 5 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| DrKrishnan |
Dr. Rai Memorial medical Centre |
No. 562, Century Plaza, Anna salai, Teynampet-600018
Chennai
TAMIL NADU |
09952933735
krishnan_dr@yahoo.com |
| DrKamalaksha Shenoy |
Kasturba Medical College and Hospital |
Attavar, Mangalore-575001
Bangalore
KARNATAKA |
09880167140
shenoykrs@rediffmail.com |
| Dr SP Shrivastav |
Lions Cancer Detection Centre |
New Civil Hospital Campus,Majura Gate,Gujarat, India
Surat
GUJARAT |
09824196710
liononco@gmail.com |
| Dr J K Singh |
Mahavir cancer sansthan |
Pulvarisharif, Patna, Bihar, 801505
Patna
BIHAR |
09431021001
drjksingh147@gmail.com |
| Dr Rajnish Nagarkar |
Manavata Curie Cancer Center |
Professional Ethics Committee,Opposite Mahamarg Bus Stand,Mumbai Naka,422004,
Nashik
MAHARASHTRA |
02532592666
drrajnagarkar@yahoo.co.in |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 5 |
| Name of Committee |
Approval Status |
| Dr Rai Memorail Medical Centre- IRB,Chennai-600018 |
Approved |
| Institutional Ethics Committee,Mangalore-575001, Karnataka |
Approved |
| Mahaver cancer institute and research centre,Patna-801505, Bihar |
Approved |
| Professional Ethics Committee, Manavata Clinical Research Institute,Mumbai Naka, Nasik 422004 |
Approved |
| Research Independent Ethics Committee,223, Meghani Tower, Surat |
Approved |
|
Regulatory Clearance Status from DCGI
Modification(s)
|
|
Health Condition / Problems Studied
Modification(s)
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C509||Malignant neoplasm of breast of unspecified site, |
|
Intervention / Comparator Agent
Modification(s)
|
| Type |
Name |
Details |
| Intervention |
Endoxifen |
Endoxifen Enteric coated Tablets 1mg and 2 mg,
Manufactured by Intas Pharmaceuticals Ltd., India.
|
| Comparator Agent |
NIL |
NIL |
|
Inclusion Criteria
Modification(s)
|
| Age From |
18.00 Year(s) |
| Age To |
70.00 Year(s) |
| Gender |
Female |
| Details |
1. The patient willing to give written informed consent to participate in the study before initiating any study related procedures.
2. 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.
6. Pt must have negative serum pregnancy test at screening (need not to be performed for postmenopausal women). |
|
| ExclusionCriteria |
| Details |
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. |
|
Method of Generating Random Sequence
Modification(s)
|
Other |
Method of Concealment
Modification(s)
|
Other |
Blinding/Masking
Modification(s)
|
Open Label |
Primary Outcome
Modification(s)
|
| Outcome |
TimePoints |
| 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
Modification(s)
|
| Outcome |
TimePoints |
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. |
28 days |
|
Target Sample Size
Modification(s)
|
Total Sample Size="18"
Sample Size from India="18"
Final Enrollment numbers achieved (Total)= ""
Final Enrollment numbers achieved (India)="" |
Phase of Trial
Modification(s)
|
Phase 1 |
Date of First Enrollment (India)
Modification(s)
|
08/02/2011 |
| Date of Study Completion (India) |
Date Missing |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Date Missing |
Estimated Duration of Trial
Modification(s)
|
Years="0"
Months="9"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Completed |
Publication Details
Modification(s)
|
NA |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
Brief Summary
Modification(s)
|
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 |