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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Onconova Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT00856791
First received: March 4, 2009
Last updated: January 7, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Ovarian Cancer
Drug: ON 01910.Na
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Single-arm Study of ON 01910.Na by 2-hr Infusion in Patients With Recurring Platinum-resistant Ovarian Cancer

Resource links provided by NLM:


Further study details as provided by Onconova Therapeutics, Inc.:

Primary Outcome Measures:
  • Progression Free Survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of Adverse Events [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 1
Study Start Date: March 2009
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
  • rigosertib sodium

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00856791

Locations
United States, Indiana
St. Vincent Gynecologic Oncology
Indianapolis, Indiana, United States, 46260
Sponsors and Collaborators
Onconova Therapeutics, Inc.
Investigators
Principal Investigator: Gregory P. Sutton, MD St. Vincent Gynecologic Oncology, Indianapolis, IN
  More Information

Additional Information:
Publications:
Responsible Party: Onconova Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT00856791     History of Changes
Other Study ID Numbers: Onconova 04-12
Study First Received: March 4, 2009
Results First Received: November 27, 2012
Last Updated: January 7, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Onconova Therapeutics, Inc.:
Ovarian
Cancer
Cisplatin
Carboplatin

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders

ClinicalTrials.gov processed this record on July 20, 2014