| CTRI Number |
CTRI/2010/091/001281 [Registered on: 14/09/2010] |
| Last Modified On: |
18/06/2015 |
| 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)
|
Research study to assess safety & efficacy in patients which are facing recurrence of ovarian cancer and are resistant to already established platinum based therapy by administering 4 hr infusion of ON 01910.Na |
Scientific Title of Study
Modification(s)
|
Phase II single-arm study of ON 01910.Na BY 4 HOUR INFUSION in patients with recurring platinum-resistant ovarian cancer |
| Trial Acronym |
Nil |
Secondary IDs if Any
Modification(s)
|
| Secondary ID |
Identifier |
| 04-12(A) |
Protocol Number |
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)
|
| Name |
Dr Suresh H Advani |
| Designation |
Director, Department of Oncology |
| Affiliation |
Jaslok Hospital & Research Centre |
| Address |
Jaslok Hospital & Research Centre 15,
Dr. G. Deshmukh Marg, Mumbai-400026, India.
Mumbai
MAHARASHTRA
400026
India |
| Phone |
91-22-66573232 |
| Fax |
91-22-23520508 |
| Email |
shadvani2000@yahoo.com |
|
Details of Contact Person
Scientific Query
Modification(s)
|
| Name |
Dr Manmohan Acharya |
| Designation |
General Manager, India |
| Affiliation |
Onconoca Therapeutics, Inc. |
| Address |
2nd Floor, 56-B, Shiv Colony,
New Sanganer Road, Sodala,
INDIA
Jaipur
RAJASTHAN
302019
India |
| Phone |
91-141-4036359 |
| Fax |
|
| Email |
macharya@onconova.us |
|
Details of Contact Person
Public Query
Modification(s)
|
| Name |
Dr Manmohan Acharya |
| Designation |
General Manager, India |
| Affiliation |
Onconoca Therapeutics, Inc. |
| Address |
2nd Floor, 56-B, Shiv Colony,
New Sanganer Road, Sodala,
INDIA
Jaipur
RAJASTHAN
302019
India |
| Phone |
91-141-4036359 |
| Fax |
|
| Email |
macharya@onconova.us |
|
Source of Monetary or Material Support
Modification(s)
|
| Onconova Therapeutics. Inc.,
73 Route 31 North
Pennington, NJ 08534, United States.
Contact No.: +1-215-527-6919
|
|
Primary Sponsor
Modification(s)
|
| Name |
Onconova Therapeutics Inc |
| Address |
Onconova Therapeutics. Inc.,
73 Route 31 North
Pennington, NJ 08534, United States.
Contact No.: +1-215-527-6919
|
| Type of Sponsor |
Pharmaceutical industry-Global |
|
Details of Secondary Sponsor
Modification(s)
|
| Name |
Address |
| Max Neeman International |
Max Neeman International
Max House 1, Dr. Jha Marg,
Okhla Phase III,
New Delhi – 110020, India
Contact No.: +91-11-40772100
Fax No.: +91-11-41814959
|
|
Countries of Recruitment
Modification(s)
|
India |
Sites of Study
Modification(s)
|
| No of Sites = 2 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| 71/1, Humayun Kabir Sarani |
B. P. Poddar Hospital & Medical Research Ltd. |
Block - G, New Alipore ,Near Durgapur Bridge -700053
Kolkata
WEST BENGAL |
+91-9051099000
+91-33-24577009
chanchalg@sify.com |
| Dr. Ashis Mukhopadhyay |
Netaji Subhash Chandra Bose Cancer Research Institute |
Gynaecological Oncology Section 16 A,Park Lane, Park street-70001
Kolkata
WEST BENGAL |
: +91-98300020196
+91-33-22264704
somashis@vsnl.net |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 2 |
| Name of Committee |
Approval Status |
| B. P. Poddar Hospital & Medical Research Ltd |
Approved |
| Netaji Subhash Chandra Bose Cancer Research Institute |
Approved |
|
Regulatory Clearance Status from DCGI
Modification(s)
|
|
Health Condition / Problems Studied
Modification(s)
|
| Health Type |
Condition |
| Patients |
Recurring platinum-resistant ovarian cancer, |
|
Intervention / Comparator Agent
Modification(s)
|
| Type |
Name |
Details |
| Intervention |
Company Serial No.: ON 01910.Na
Chemical Name: sodium salt of (E)-2,4,6-trimethoxystyryl-3-carboxymethylamino-4-
methoxybenzyl sulfone
|
Dose: 2400mg biweekly for 3 weeks in 4 weeks Cycle for 6 months
Indication: Platinum resistant ovarian cancer
|
| Comparator Agent |
Not Applicable |
Not Applicable |
|
Inclusion Criteria
Modification(s)
|
| Age From |
18.00 Year(s) |
| Age To |
65.00 Year(s) |
| Gender |
Female |
| Details |
1. Women with ovarian cancer aged greater than or equal to 18 yeras to les than or equal to 65 years with measurable disease who have shown recurrent disease within 6 months of the last dose of cisplatin- or carboplatin-based chemotherapy.
a. Measurable disease will be defined as lesions that can be accurately measured in at least one dimension with longest diameter greater than or equal to 20 mm using conventional techniques or gretaer than or equal to 10 mm with spiral CT scan.
2. Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1 or 2 (see Attachment 1 of Protocol).
3. No more than 3 prior chemotherapy regimens.
4. Disease-free period of more than 5 years from prior malignancies other than ovarian (except curatively treated basal cell carcinoma, squamous cell carcinoma of the skin or carcinoma in situ of the cervix).
5. All patients of childbearing potential must use at least one form of contraception as approved by the Investigator prior to study and up to 30 days beyond the last administration of study drug.
6. Women of childbearing potential must have a negative serum betaHCG pregnancy test at screening.
7. Willing to adhere to the prohibitions and restrictions specified in this protocol.
8. Patient (or her legally authorized representative) must have signed an informed consent document
|
|
| ExclusionCriteria |
| Details |
1. Evidence of complete or partial bowel obstruction.
2. Need for IV hydration or Total Parenteral Nutrition.
3. Inability to comply with study and/or follow-up procedures.
4. Life expectancy of less than 12 weeks.
5. Prior radiotherapy to greater than one third of hematopoietic sites.
6. Uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia.
7. Active infection not adequately responding to appropriate therapy.
8. Hyponatremia (defined as serum sodium value of 134 mEq/L)
9. Total bilirubin greater than or equal to 1.5 mg/dL not related to hemolysis or Gilbert?s disease, AST/ALT or alkaline phosphatase greater than or equal to 2 X upper limit of normal (ULN).
10. Serum creatinine greater than or equal to 2.0 mg/dL.
11. ANC 1500/mm3, platelets 100,000/mm3; hemoglobin less than 9 g/dL.
12. Ascites requiring active medical management including paracentesis for more than twice a month.
13. Women patients who are pregnant or lactating or have a positive serum betaHCG pregnancy test at screening.
14. Major surgery without full recovery or major surgery within 3 weeks of ON 01910.Na treatment start.
15. Uncontrolled hypertension (defined as a systolic pressure greater than or equal to 160 and/or a diastolic pressure greater than or equal to 110).
16. New onset seizures (within 3 months prior to the first dose of ON 01910.Na) or poorly controlled seizures.
17. Brain metastases including any of the following:
a. Evidence of cerebral edema by CT scan or MRI
b. Evidence of disease progression on prior imaging studies
c. Requirement for steroids
d. Clinical symptoms of brain metastases
18. Any concurrent, and/or within 4 weeks of the first dose of study drug, investigational agent or chemotherapy, radiotherapy or immunotherapy
19. Psychiatric illness/social situations that would limit the patients ability to tolerate and/or comply with study requirements
|
|
Method of Generating Random Sequence
Modification(s)
|
Not Applicable |
Method of Concealment
Modification(s)
|
Not Applicable |
Blinding/Masking
Modification(s)
|
Open Label |
Primary Outcome
Modification(s)
|
| Outcome |
TimePoints |
| Progression free survival (PFS) rates in patients with platinum-resistant ovarian cancer |
24 weeks |
|
Secondary Outcome
Modification(s)
|
| Outcome |
TimePoints |
2.Tolerability of ON 01910.Na
(where CR: Complete Response, PR: Partial Response, SD: Stable Disease)
|
During the Entire study duration |
| 1.Objective response rates (ORR), duration of response, duration of stable disease, clinical benefit [CR+PR+SD] and overall survival [OS] |
At 2 months, 4 months, 6 months |
|
Target Sample Size
Modification(s)
|
Total Sample Size="37"
Sample Size from India="37"
Final Enrollment numbers achieved (Total)= ""
Final Enrollment numbers achieved (India)="" |
Phase of Trial
Modification(s)
|
Phase 2 |
Date of First Enrollment (India)
Modification(s)
|
27/09/2010 |
| 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="1"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Completed |
Publication Details
Modification(s)
|
none as yet |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
Brief Summary
Modification(s)
|
It is phase II, single arm, open label study. Patients having platinum resistant ovarian cancer with recurrence within 6 months of the last dose of cisplatin or carboplatin (or any platinum -based chemotherapy); no more than 3 prior chemotherapies will be taken for the study. Total of thirty-seven (37) patients will be treated with 2400 mg ON 01910.Na administered as a 4-hour infusion on Days 1, 4, 8, 11, 15 and 18 of a 28-day cycle until disease progression or withdrawal for other causes (unacceptable toxicity, patient or investigator decision) with ON 01910.Na. A futility analysis will be performed after 17 evaluable patients are enrolled and evaluated for overall objective response, If 3 or fewer objective responses are observed, the study will be closed to further accrual and deemed futile. An extension study for an additional 25 weeks with monitoring according to the Time and Events Schedule will be considered for patients who have not progressed by week 25
Investigation product is ON 01910.Na, it a novel benzyl styryl sulfone, is under development as an anti-cancer agent. ON 01910.Na has a differential effect on cell cycle progression in tumor cells vs. normal cells. It acts on tumor cells primarily by inhibition of cell cycle progression at the G2-M stages. Chromosomes disperse in the cytoplasm, followed by apoptosis. Normal cells, however, are reversibly arrested at G1 and G2, without apoptosis. Unlike previously reported small molecule kinase inhibitors, which interact at the ATP binding site, ON 01910.Na competes against substrate (Gumireddy et al. 2005). ON 01910.Na may operate through a novel molecular mechanism, which is currently under evaluation, and thus may have activity against tumors refractory to existing marketed drugs.
The Primary Objectives: is to determine the progression free survival (PFS) rates in patients with platinum-resistant ovarian cancer, after 24 weeks of treatment with ON 01910.Na
The secondary objectives are:
a. To document other measures of outcome: objective response rates (CR+PR), duration of response, duration of stable disease (CR, PR, SD), and clinical benefit rate (complete response[CR]+partial response[PR]+stable disease[SD] using RECIST guidelines and overall survival)
b. To document the tolerability of ON 01910.Na
(CR: Complete Response, PR: Partial Response, SD: Stable Disease)
Criteria for Evaluation is as follows:
1. Efficacy The following end points will be assessed:
a. Progression free survival
b. Objective tumor response at 25 weeks using RECIST guidelines on CT scan
c. Duration of response (CR+PR)
d. Duration of stable disease
e. Overall survival
f. Clinical benefit (CR+PR+SD)
2. Safety
a. History and physical examination, vital signs, weight
b. Laboratory evaluations
c. Toxicity and adverse event assessments |