Effect of 2-h Infusion of ON 01910.Na in Ovarian Cancer Patients

June 22, 2017 updated by: Onconova Therapeutics, Inc.

Phase II Single-arm Study of ON 01910.Na by 2-hr Infusion in Patients With Recurring Platinum-resistant Ovarian Cancer

ON 01910.Na has undergone preclinical and clinical phase I studies showing activity in patients with progressing ovarian cancer resistant to platinum-based chemotherapies. This study will look at a larger population of patients to determine whether treatment with ON 01910.Na has an effect on progression free survival rates in patients with platinum-resistant ovarian cancer. ON 01910.Na will be given as an intravenous infusion over 2 hours on days 1, 4, 8, 11, 15, and 18 of a 28-day cycle. Patients will be treated for 6 or more cycles.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a Phase II single arm study of ON 01910.Na to be administered as a 2-hour infusion biweekly to patients with progressive ovarian cancer resistant to platinum-based therapy.

The primary objective is to evaluate progression-free survival (PFS). The secondary objectives are to document other measures of outcome [objective response rate (ORR), duration of response, duration of stable disease, and overall survival (OS)], and tolerability of study drug.

Thirty-seven (37) patients with progressive ovarian cancer resistant to platinum-based therapy will be enrolled in a single arm study and treated with ON 01910.Na administered as a 2-hour infusion on Days 1, 4, 8, 11, 15 and 18 of a 28-day cycle. Patients will be treated until disease progression or withdrawal for other causes (unacceptable toxicity, patient or investigator decision) with ON 01910.Na. Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v3.0). Progression-free survival, objective response, duration of response, and duration of stable disease will be assessed using RECIST (Response Evaluation Criteria in Solid Tumor) guidelines, as well as overall survival. Grades 3 and 4 hematologic toxicities, grade >2 non-hematologic toxicities will be monitored. A futility analysis will be performed after 17 evaluable patients are enrolled and evaluated for overall objective response. If 3 or fewer objective response (CR and PR) are observed, the study will be closed to further accrual and deemed futile. An extension study for an additional 25 weeks with complete monitoring will be considered for patients who have not progressed by week 25.

The ON 01910.Na dose to be used in this study (2-hour infusions of 2400 or 3200 mg twice weekly for 3 weeks of a 4-week cycle) was selected based on the maximum tolerated doses and activities documented in phase 1 protocols.

Study Type

Interventional

Enrollment (Actual)

1

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Indiana
      • Indianapolis, Indiana, United States, 46260
        • St. Vincent Gynecologic Oncology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Women with ovarian cancer at least 18 years old 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 ≥ 20 mm using conventional techniques or ≥ 10 mm with spiral CT scan.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1 or 2.
  • 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 female patients of childbearing potential must use at least one form of contraception as approved by the Investigator prior to study entry and for up to 30 days beyond the last administration of study drug.
  • Women of childbearing potential must have a negative serum βHCG pregnancy test at screening.
  • Willing to adhere to the prohibitions and restrictions specified in this protocol.
  • Patient (or her legally authorized representative) must have signed an informed consent document.

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.
  • Hyponatremia (defined as serum sodium value of <134 mEq/L).
  • Total bilirubin ≥ 1.5 mg/dL not related to hemolysis or Gilbert's disease, AST/ALT or alkaline phosphatase ≥ 2 X ULN.
  • Serum creatinine ≥ 2.0 mg/dL.
  • 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 βHCG 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 ≥ 160 and/or a diastolic pressure ≥ 110).
  • New onset seizures (within 3 months prior to the first dose of ON 01910.Na) or poorly controlled seizures.

  • Brain metastases including any of the following:

    1. Evidence of cerebral edema by CT scan or MRI.
    2. Evidence of disease progression on prior imaging studies.
    3. Requirement for steroids.
    4. Clinical symptoms of brain metastases.
  • Any concurrent and/or within 4 weeks of the first dose of study drug investigational agent or chemotherapy, radiotherapy or immunotherapy.
  • Psychiatric illness/social situations that would limit the patient's ability to tolerate and/or comply with study requirements.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ON 01910.Na
3200 mg ON 01910.Na administered intravenously over 2 hours on days 1, 4, 8, 11, 15, and 18 of 28-day cycle
Drug: ON 01910.Na
Other Names:
  • rigosertib sodium
  • rigosertib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival
Time Frame: 6 months
Progression-free survival, defined as the number of days from the first day of study drug dosing to the day of documented disease progression or death, as assessed using RECIST (Response Evaluation Criteria in Solid Tumors) guidelines according to Therasse P, Arbuck SF, Eisenhauer EA, et al. (2000) J Natl Cancer Inst. 92:205-216. Progressive disease is defined as at least a 20% increase in the sum of the longest diameter (LD)of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Adverse Events
Time Frame: 6 months
The number of adverse events and their severity rating will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, version 3.0.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Onconova Therapeutics, Inc.

Investigators

  • Principal Investigator: Gregory P. Sutton, MD, St. Vincent Gynecologic Oncology, Indianapolis, IN

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2009

Primary Completion (Actual)

July 1, 2011

Study Completion (Actual)

July 1, 2011

Study Registration Dates

First Submitted

March 4, 2009

First Submitted That Met QC Criteria

March 4, 2009

First Posted (Estimate)

March 6, 2009

Study Record Updates

Last Update Posted (Actual)

July 21, 2017

Last Update Submitted That Met QC Criteria

June 22, 2017

Last Verified

June 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Onconova 04-12

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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