Ovarian CancerPhase 2NCT00856791
Effect of 2-h Infusion of ON 01910.Na in Ovarian Cancer Patients
A Phase 2 study testing ON 01910.Na in people with Ovarian Cancer, run by Traws Pharma, Inc. at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Ovarian Cancer
- What is being tested?
- ON 01910.Na
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2009to Jul 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 23Show fewer
- 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:
- Evidence of cerebral edema by CT scan or MRI.
- Evidence of disease progression on prior imaging studies.
- Requirement for steroids.
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
St. Vincent Gynecologic Oncology
Indianapolis, Indiana, 46260
About this study
Official title: 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.
Read the 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.
- Conditions
- Ovarian Cancer
- Being tested
- ON 01910.Na
- Keywords
- Ovarian, Cancer, Cisplatin, Carboplatin
- Medical subject headings
- Ovarian Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ON 01910.NaDrug
Also called rigosertib, rigosertib sodium
| Study group | Role | What they receive |
|---|---|---|
| ON 01910.Na | Experimental | 3200 mg ON 01910.Na administered intravenously over 2 hours on days 1, 4, 8, 11, 15, and 18 of 28-day cycle Receives: Drug: ON 01910.Na |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival
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.
Measured: 6 months
Secondary outcomes (1)
Number of Adverse Events
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.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2009 (estimated)
- Study startMar 2009
- Primary completionJul 2011
- Study completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Ovarian CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Traws Pharma, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gregory P. Sutton, MD, Principal investigator, St. Vincent Gynecologic Oncology, Indianapolis, IN
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00856791
- Sponsor's protocol ID
- Onconova 04-12
- Status last verified
- Jun 2017
- First submitted
- 4 Mar 2009
- Last updated
- 21 Jul 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Jimeno A, Li J, Messersmith WA, Laheru D, Rudek MA, Maniar M, Hidalgo M, Baker SD, Donehower RC. Phase I study of ON 01910.Na, a novel modulator of the Polo-like kinase 1 pathway, in adult patients with solid tumors. J Clin Oncol. 2008 Dec 1;26(34):5504-10. doi: 10.1200/JCO.2008.17.9788. Epub 2008 Oct 27.
PubMed 18955447Jimeno A, Chan A, Cusatis G, Zhang X, Wheelhouse J, Solomon A, Chan F, Zhao M, Cosenza SC, Ramana Reddy MV, Rudek MA, Kulesza P, Donehower RC, Reddy EP, Hidalgo M. Evaluation of the novel mitotic modulator ON 01910.Na in pancreatic cancer and preclinical development of an ex vivo predictive assay. Oncogene. 2009 Jan 29;28(4):610-8. doi: 10.1038/onc.2008.424. Epub 2008 Nov 24.
PubMed 19029951Reddy MV, Mallireddigari MR, Cosenza SC, Pallela VR, Iqbal NM, Robell KA, Kang AD, Reddy EP. Design, synthesis, and biological evaluation of (E)-styrylbenzylsulfones as novel anticancer agents. J Med Chem. 2008 Jan 10;51(1):86-100. doi: 10.1021/jm701077b. Epub 2007 Dec 19.
PubMed 18088089Gumireddy K, Reddy MV, Cosenza SC, Boominathan R, Baker SJ, Papathi N, Jiang J, Holland J, Reddy EP. ON01910, a non-ATP-competitive small molecule inhibitor of Plk1, is a potent anticancer agent. Cancer Cell. 2005 Mar;7(3):275-86. doi: 10.1016/j.ccr.2005.02.009.
PubMed 15766665Garcia-Manero G, Fenaux P. Comprehensive Analysis of Safety: Rigosertib in 557 Patients with Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML). Blood Dec 2016, 128 (22) 2011; ASH 2016.
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Single-arm Study of ON 01910.Na by 2-hr Infusion in Patients With Recurring Platinum-resistant Ovarian Cancer
- ClinicalTrials.gov ID
- NCT00856791
- Acronym / sponsor ID
- Onconova 04-12
- Conditions
- Ovarian Cancer
- Keywords
- Ovarian, Cancer, Cisplatin, Carboplatin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Traws Pharma, Inc.Industry (pharma, biotech, devices)
- Study start
- Mar 2009
- Primary completion
- Jul 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 6 Mar 2009 (estimated)
- Results
- Posted 8 Jan 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ON 01910.Na | Experimental | Drug: ON 01910.Na3200 mg ON 01910.Na administered intravenously over 2 hours on days 1, 4, 8, 11, 15, and 18 of 28-day cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (23 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ON 01910.NaAlso: rigosertib, rigosertib sodium | Drug | ON 01910.Na |
Primary outcome
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.
1 secondary outcome
Number of Adverse Events
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 18955447Jimeno A, Li J, Messersmith WA, Laheru D, Rudek MA, Maniar M, Hidalgo M, Baker SD, Donehower RC. Phase I study of ON 01910.Na, a novel modulator of the Polo-like kinase 1 pathway, in adult patients with solid tumors. J Clin Oncol. 2008 Dec 1;26(34):5504-10. doi: 10.1200/JCO.2008.17.9788. Epub 2008 Oct 27.
- Background: PubMed 19029951Jimeno A, Chan A, Cusatis G, Zhang X, Wheelhouse J, Solomon A, Chan F, Zhao M, Cosenza SC, Ramana Reddy MV, Rudek MA, Kulesza P, Donehower RC, Reddy EP, Hidalgo M. Evaluation of the novel mitotic modulator ON 01910.Na in pancreatic cancer and preclinical development of an ex vivo predictive assay. Oncogene. 2009 Jan 29;28(4):610-8. doi: 10.1038/onc.2008.424. Epub 2008 Nov 24.
- Background: PubMed 18088089Reddy MV, Mallireddigari MR, Cosenza SC, Pallela VR, Iqbal NM, Robell KA, Kang AD, Reddy EP. Design, synthesis, and biological evaluation of (E)-styrylbenzylsulfones as novel anticancer agents. J Med Chem. 2008 Jan 10;51(1):86-100. doi: 10.1021/jm701077b. Epub 2007 Dec 19.
- Background: PubMed 15766665Gumireddy K, Reddy MV, Cosenza SC, Boominathan R, Baker SJ, Papathi N, Jiang J, Holland J, Reddy EP. ON01910, a non-ATP-competitive small molecule inhibitor of Plk1, is a potent anticancer agent. Cancer Cell. 2005 Mar;7(3):275-86. doi: 10.1016/j.ccr.2005.02.009.
- Results publicationGarcia-Manero G, Fenaux P. Comprehensive Analysis of Safety: Rigosertib in 557 Patients with Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML). Blood Dec 2016, 128 (22) 2011; ASH 2016.
- Website of St. Vincent Health, one of the clinical sites conducting the study. Information about St. Vincent Health, links to other related sites.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gregory P. Sutton, MD principal investigator
St. Vincent Gynecologic Oncology, Indianapolis, IN
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ON 01910.Na in people with Ovarian Cancer, run by Traws Pharma, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jan 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00856791, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2017.