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

Phase 2

Completed

Conditions: Recurring platinum-resistant ovarian cancer

Registration Number: CTRI/2010/091/001281

Lead Sponsor: Onconova Therapeutics Inc

Brief Summary: 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

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Female

Target Recruitment: 37

Inclusion Criteria

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.
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.
Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1 or 2 (see Attachment 1 of Protocol).
No more than 3 prior chemotherapy regimens.
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).
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.
Women of childbearing potential must have a negative serum betaHCG pregnancy test at screening.
Willing to adhere to the prohibitions and restrictions specified in this protocol.

Exclusion Criteria

Evidence of complete or partial bowel obstruction.
Need for IV hydration or Total Parenteral Nutrition.
Inability to comply with study and/or follow-up procedures.
Life expectancy of less than 12 weeks.
Prior radiotherapy to greater than one third of hematopoietic sites.
Uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia.
Active infection not adequately responding to appropriate therapy.
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).
ANC 1500/mm3, platelets 100,000/mm3; hemoglobin less than 9 g/dL.
Ascites requiring active medical management including paracentesis for more than twice a month.
Women patients who are pregnant or lactating or have a positive serum betaHCG pregnancy test at screening.
Major surgery without full recovery or major surgery within 3 weeks of ON 01910.Na treatment start.
Uncontrolled hypertension (defined as a systolic pressure greater than or equal to 160 and/or a diastolic pressure greater than or equal to 110).
New onset seizures (within 3 months prior to the first dose of ON 01910.Na) or poorly controlled seizures.
Evidence of cerebral edema by CT scan or MRI b.
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.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Progression free survival (PFS) rates in patients with platinum-resistant ovarian cancer	24 weeks

Secondary Outcome Measures

Name	Time	Method
2.Tolerability of ON 01910.Na	(where CR: Complete Response, PR: Partial Response, SD: Stable Disease)
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

Trial Locations

Locations (2): B. P. Poddar Hospital & Medical Research Ltd.
🇮🇳
Kolkata, WEST BENGAL, India
Netaji Subhash Chandra Bose Cancer Research Institute
🇮🇳
Kolkata, WEST BENGAL, India
B. P. Poddar Hospital & Medical Research Ltd.
🇮🇳Kolkata, WEST BENGAL, India
71/1, Humayun Kabir Sarani
Principal investigator
91-9051099000
chanchalg@sify.com