| CTRI Number |
CTRI/2011/12/002225 [Registered on: 14/12/2011] Trial Registered Prospectively |
| Last Modified On: |
22/06/2012 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Single Arm Study |
|
Public Title of Study
|
A Phase 1 Study for patients with advanced solid tumors. |
|
Scientific Title of Study
|
A Phase 1 Dose-Escalation Study of the Safety and
Pharmacokinetics of Daily OCID 4681-S-01 Administered Orally to Subjects with Advanced Solid Tumors |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| OCID4681-S-01 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Priyanka Chauhan |
| Designation |
Head Clinical Operations |
| Affiliation |
|
| Address |
Veeda Clinical Research Pvt Ltd,
Nilkamal House, Ground Floor,
Plot no 77/78, Road no 13-14,
MIDC, Andheri (E), Mumbai, India
Veeda Clinical Research Pvt Ltd,
Nilkamal House, Ground Floor,
Plot no 77/78, Road no 13-14,
MIDC, Andheri (E), Mumbai, India
Mumbai
MAHARASHTRA
400093
India |
| Phone |
02230033030 |
| Fax |
02230033001 |
| Email |
priyanka.chauhan@veedaoncology.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Priyanka Chauhan |
| Designation |
Head Clinical Operation |
| Affiliation |
|
| Address |
Veeda Clinical Research Pvt Ltd,
Nilkamal House, Ground Floor,
Plot no 77/78, Road no 13-14,
MIDC, Andheri (E), Mumbai, India
Veeda Clinical Research Pvt Ltd,
Nilkamal House, Ground Floor,
Plot no 77/78, Road no 13-14,
MIDC, Andheri (E), Mumbai, India
Mumbai
MAHARASHTRA
400093
India |
| Phone |
02230033030 |
| Fax |
02230033001 |
| Email |
priyanka.chauhan@veedaoncology.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Priyanka Chauhan |
| Designation |
Director |
| Affiliation |
|
| Address |
Veeda Clinical Research Pvt Ltd,
Nilkamal House, Ground Floor,
Plot no 77/78, Road no 13-14,
MIDC, Andheri (E), Mumbai, India
Veeda Clinical Research Pvt Ltd,
Nilkamal House, Ground Floor,
Plot no 77/78, Road no 13-14,
MIDC, Andheri (E), Mumbai, India
Mumbai
MAHARASHTRA
400093
India |
| Phone |
02230033030 |
| Fax |
02230033001 |
| Email |
priyanka.chauhan@veedaoncology.com |
|
|
Source of Monetary or Material Support
|
| Orchid Research Laboratories Ltd, Plot no 476/17A Old Mahabalipuram Road, Sholinganallur, Chennai - 600 119, Tamil Nadu, India |
|
|
Primary Sponsor
|
| Name |
Orchid Research Laboratories Ltd |
| Address |
Plot no 476/17A Old Mahabalipuram Road, Sholinganallur, Chennai - 600 119, Tamil Nadu, India |
| Type of Sponsor |
Pharmaceutical industry-Indian |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
Sites of Study
Modification(s)
|
| No of Sites = 4 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Venkatesan Srinivasan |
Dr Kamakshi Memorial Hospital |
1, Radial Road, Pallikaranai
Chennai 600100,
Chennai
TAMIL NADU |
91-44-66300300
vsrinivasan09@gmail.com |
| Dr Raghunadharao |
Nizams Institute of Medical Sciences |
Department of Oncology, Room no 607, 6th Floor, E block, Panjagutta
Hyderabad
ANDHRA PRADESH |
04023489360
04023371747
telerama@rediffmail.com |
| Dr Minish Jain |
Ruby Hall Clinic |
Department of Oncology, New Cancer Building, 3rd Floor, 40 Sassoon Road, Pune 411001
Pune
MAHARASHTRA |
9823133390
02026124529
minishjain009@gmail.com |
| Dr Kumar Prabhash |
Tata Memorial Hospital |
Department of Medical Oncology, Dr E Borges Road, Room no 18, Parel
Mumbai
MAHARASHTRA |
02224177214
02224171734
kp_prabhash@rediffmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 4 |
| Name of Committee |
Approval Status |
| Ethical Committee Dr Kamakshi Memorial Hospital |
Approved |
| Ethics Committee Poona Medical Research Foundation |
Approved |
| Institutional Ethical Committee, Nizam’s Institute of Medical Sciences |
Submittted/Under Review |
| Tata Memorial Hospital Scientific Review Committee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
Patients with Advance solid Tumors, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Not applicable |
Not applicable |
| Intervention |
OCID4681S01 |
OCID 4681S01 will be administered daily as an oral agent. The first cohort will be dosed at 5 mg daily subsequent cohorts will be dosed at levels outlined in section 3. Cycle length for evaluation purposes will be 28
days. A minimum of three subjects is planned for each dosing cohort with
dose escalation dependent on safety and PK data from prior cohorts. In the absence of unacceptable drug related toxicity, subjects whom the
investigator feels may be benefitting from OCID 4681S01 therapy may continue on study until either disease progression unacceptable drugrelated toxicity or the investigator feels it is no longer in the subject best
interest to continue.
OCID 4681-S-01 is supplied as 0.5, 1, 2, 5, 10, 25 and 50 mg capsules. |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
1 The subject has a histologically confirmed solid tumor that is metastatic or unresectable and is no longer responding to therapies known to prolong survival or to other standard therapies, or has disease for which no standard
therapy exists.
2 The subject is greater than or equal to 18 years old.
3 The subject has an Eastern Cooperative Oncology Group ECOG performance status of 0 to 2 Appendix B
4 Subject has a life expectancy of greater than 3 months.
5 The subject has adequate organ and marrow function as follows
Absolute neutrophil count ANC greater than or equal 1500mm3.
Platelets greater than or equal 100,000mm3.
Hemoglobin greater than or equal 10 g per dL, with no transfusions within the last seven days.
Bilirubin less than or equal 1.5 the upper limit of normal ULN.
Serum creatinine less than or equal 1.5 ULN or calculated creatinine clearance greater than or equal 60 mL per min.
Alanine aminotransferase ALT and aspartate aminotransferase AST
less than or equal 2.5 ULN if no liver involvement, or less than or equal 5 ULN with liver involvement.
6 The subject is able to swallow and tolerate oral medications such as capsules.
7 The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document.
8 Sexually active subjects men and women must agree to use medicallyaccepted barrier methods of contraception eg, male condom, female
condom, or diaphragm with spermicidal gel during the course of the study and for 3 months after the last dose of study drugs, even if oral contraceptives are also used. All subjects of reproductive potential must agree to use both a barrier method and a second method of birth control.
9 Women of childbearing potential must have a negative pregnancy test at screening. Women of childbearing potential include any woman who has
experienced menarche and who has not undergone successful surgical sterilization hysterectomy, bilateral tubal ligation, or bilateral oophorectomy or is not postmenopausal. Post menopause is defined as
Amenorrhea greater than or equal 12 consecutive months without another cause or
For women with irregular menstrual periods and on hormone replacement therapy, a documented serum follicle stimulating hormone FSH level 35 mIU per mL. |
|
| ExclusionCriteria |
| Details |
1 The subject has received cytotoxic chemotherapy including investigational cytotoxic chemotherapy or biologic agents eg, cytokines or antibodies within 3 weeks, or nitrosoureas or
mitomycin C within 6 weeks before the first dose of study treatment.
2 The subject has received radiation therapy within 14 days of the first dose of study treatment. Palliative radiation to nonmarrow areas is allowed.
3 The subject has received any other type of investigational agent within 28 days before the first dose of study treatment.
4 The subject has not recovered from toxicity due to all prior therapies ie, return to pretherapy baseline or to Grade 0 or 1
5 The subject has received lifetime radiation to 25 percent of his or her bone marrow before the first dose of study treatment.
6 The subject has a primary brain tumor or brain metastases.
7 The subject has prothrombin time PT International Normalized Ratio INR or partial thromboplastin time PTT test results at screening that are 1.3 times the laboratory ULN.
8 The subject has uncontrolled significant intercurrent illness including, but not limited to ongoing or active infection, history of congestive heart failure within 6 months, uncontrolled hypertension or unstable angina pectoris within 6 months, stroke within 3 months, myocardial infarction within 3 months, or cardiac arrhythmias.
9 The subject is pregnant or breastfeeding.
10 The subject tests positive for the human immunodeficiency virus HIV, Hepatitis B virus (HBV) or Hepatitis C virus HCV at screening.
11 The subject has a previously identified allergy or hypersensitivity to components of the study treatment formulation.
12 The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee |
|
|
Method of Generating Random Sequence
|
Not Applicable |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Not Applicable |
|
Primary Outcome
|
| Outcome |
TimePoints |
The primary objectives of this study in patients with solid tumors are as follows:
? Evaluate the safety and tolerability of daily oral administration of OCID
4681-S-01.
? Determine the MTD of daily oral administration of OCID 4681-S-01.
? Determine the safety profile and most common dose-limiting toxicities (DLTs) of daily oral administration of OCID 4861.
? Evaluate the plasma pharmacokinetics of daily oral administration of OCID 4681-S-01. |
Although all subjects may continue to receive study treatment until
experiencing toxicity or disease progression it is estimated that each
subject will participate for an average of 2 to 4 months of treatment with an
additional 1 month of followup. |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
The secondary objectives of this study are as follows:
• To evaluate tumor response (preliminary antitumor activity) after repeated
oral administration of OCID 4681-S-01
• To evaluate biomarker correlates (H3A, p21 expression, HbF concentration) of OCID 4681-S-01 activity.
• To evaluate preliminary PK/PD relationships and explore plasma concentration and time vs. biomarker activity. |
Although all subjects may continue to receive study treatment until
experiencing toxicity or disease progression it is estimated that each
subject will participate for an average of 2 to 4 months of treatment with an
additional 1 month of followup. |
|
|
Target Sample Size
|
Total Sample Size="36"
Sample Size from India="36"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 1 |
|
Date of First Enrollment (India)
|
23/01/2012 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
Not applicable |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
OCID 4681–S-01 is an HDAC inhibitor which is believed to have significant anti-tumor activity. Based on preclinical studies result, OCID 4681-S-01 is known to promote histone acetylation and increase expression of the growth suppressor gene p21, which have been shown to increase cellular apoptosis and inhibit growth in tumor cells. These properties make OCID 4681-S-01 a good candidate for testing in humans for anti-cancer activity. Chemically, OCID 4681-S-01 is (E)-N-(2-aminophenyl)-4-(3-(cyclopropylamino)-2-(4-fluorophenyl)-3-oxoprop-1-en-1-yl)benzamide hydrochloride. Vorinostat, a hydroxamate-based inhibitor, was the first HDACi to be approved by the Food and Drug Administration (FDA) in October 2006 for the treatment of refractory Cutaneous T-Cell lymphoma for patients who had received two or more prior systemic therapies. The trial is conducted in 3 sites in India. The sites would enroll up to 36 patients.
|