Advanced CancerPhase 1NCT01538537
Safety of ON 01910.Na as a 3-day Infusion in Patients With Advanced Cancer
A Phase 1 study testing rigosertib sodium in people with Advanced Cancer and Solid Tumors, run by Traws Pharma, Inc. at 1 site in United States.
Trial summary
The primary objective of this study is to determine the largest dose of ON 01910.Na (rigosertib sodium) that can be given safely as a 3-day continuous infusion once every 2 weeks (2-week cycle) in patients with advanced cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Cancer, Solid Tumors, Cancer
- What is being tested?
- rigosertib sodium
- Type of treatment
- Injection or infusion
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2006to Jan 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.
- At least 4 weeks since the last dose of other potentially myelosuppressive treatment (at least 6 weeks since last dose of nitrosoureas or mitomycin C) and recovery from manifestations of reversible drug toxicity (except alopecia, stable residual neuropathy, and residual hand and foot syndrome). Among patients with prior doxorubicin chemotherapy, only those with no more than 450 mg/m2 of the drug will be entered. It must be at least 4 weeks since prior chemotherapy or radiation therapy, 6 weeks if the last regimen included nitrosoureas or mitomycin C.
- Patients with prior radiotherapy are eligible provided that a minimum of 4 weeks have passed and that the maximal area of hematopoietic active bone marrow treated was less than 25%.
- ECOG performance status < 2.
- Hgb > 10 gm/dl
- WBC > 4,000 per microliter
Show all 14Show fewer
- Absolute neutrophil count > 1,500 per microliter
- Platelets >100,000 per microliter
- Total bilirubin within normal institutional limits
- AST(SGOT)/ALT(SGPT) values within limits defined by Protocol
- Creatinine within normal institutional limits or creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
- Women of child-bearing potential and men must agree to use adequate contraception.
- Ability to understand and the willingness to sign a written informed consent document.
- Inclusion Criteria - Dose Confirmation Phase Same inclusion criteria as in the Dose Escalation phase described above, except Patients must have an ECOG performance of 0 or 1.
Who cannot join
- Patients who have had recent major surgery (within the past 14 days), chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (except alopecia, stable residual neuropathy, and residual hand and foot syndrome) due to previously administered agents.
- Patients may not be receiving any other investigational agents or concurrent chemotherapy, radiotherapy, hormonal treatments, or immunotherapy while on study.
- Patients with known or clinical evidence of central nervous system metastasis, except brain metastases that have been previously removed or irradiated and currently have no clinical impact.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ON 01910.Na.
- The patient should have no major 3rd space fluid, ascites requiring active medical management including paracentesis, peripheral bilateral edema, or hyponatremia (serum sodium value less than 134 Meq/L).
- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, bleeding, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant and nursing women are excluded from this study.
- HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
Mount Sinai School of Medicine
New York, New York, 10029
About this study
Official title: Phase I Dose Escalation Study of ON 01910.Na by 3-day Continuous Infusion in Patients With Advanced Cancer
The primary objective of this study is to determine the largest dose of ON 01910.Na (rigosertib sodium) that can be given safely as a 3-day continuous infusion once every 2 weeks (2-week cycle) in patients with advanced cancer.
Read the detailed description
This was an open-label, single-center, dose-escalating Phase I study to determine the Dose-Limiting Toxicities (DLTs) and Recommended Phase 2 Dose (RPTD) of ON 01910.Na (rigosertib sodium) administered as a 3 day continuous intravenous (CIV) infusion every 2 weeks (2-week cycles) to up to 28 patients with advanced cancer (12 to 16 in the dose escalation phase and up to 12 additional patients in the dose confirmation phase). The dosing of rigosertib was based on body surface area (BSA), with a starting dose of 50 mg/m2/24 hour for 3 consecutive days.
In the absence of toxicity after at least a 3-week observation period, rigosertib doses were escalated following a Fibonacci scheme with an initial accelerated dose-escalation phase in which 1-patient cohorts received rigosertib for 3 weeks until drug-related Grade 2 toxicity (according to Common Toxicity Criteria for Adverse Events [CTCAE] v.3), excluding alopecia, occurred, at which time 2 additional patients were added to subsequent cohorts. If none of the 3 patients in the cohort experienced DLTs, the dose was escalated by a half-Fibonacci step. If a DLT was seen in the first patient of a cohort, dosing went back a half-step. The next dose level occurred if no DLT was reported in the 3 patients or if no more than 1 DLT occurred in an expanded cohort of 6 patients. If a DLT was seen in 1 of the 3 patients, 3 additional patients were enrolled in the cohort. If DLTs were seen in 2 of 6 patients in a cohort, dose escalation was stopped.
Once the maximum administered dose (MAD) was attained and the RPTD was determined, the dose escalation phase was considered complete. Up to 12 additional patients with histologically confirmed malignant tumors were tested at the RPTD dose to confirm its appropriateness.
Secondary objectives were to determine the qualitative and quantitative toxicity and reversibility of toxicity of rigosertib administered in this fashion; to investigate the clinical pharmacology of rigosertib when administered in this fashion, including plasma pharmacokinetics at each dose level; to confirm the appropriateness of the RPTD; to document any observed antitumor activity of rigosertib; and, to evaluate the biological effect of rigosertib in biomarkers in serum and/or peripheral blood mononuclear cells.
- Conditions
- Advanced Cancer, Solid Tumors, Cancer, Neoplasms
- Being tested
- rigosertib sodium
- Keywords
- ON 01910.Na, rigosertib Sodium, rigosertib
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rigosertib sodiumDrug
Also called ON 01910.Na Concentrate, ON 01910.Na, rigosertib
ON 01910.Na will be supplied as a sterile, concentrated solution (75 mg/ml) in labeled, sealed glass vials. ON 01910.Na concentrated solution (75 mg/ml) must be diluted before intravenous administration. The starting dose will be 50 mg/m2 over 24 hour infusion daily for 3 days. A fresh infusion must be prepared for each day of the 3-day continuous infusion. This 3-day continuous treatment followed by 11 days without administration of study drug will constitute 1 Cycle. Cycles can be repeated every 2 weeks. The dosing of ON 01910.Na will be based on body surface area (BSA). In the absence of toxicity that would cause accelerated dose escalation to cease, drug doses are planned to escalate every 3 weeks.
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of dose limiting toxicities (DLTs)
DLTs are defined as:
- Grade 3 non-hematological toxicity other than nausea, vomiting, diarrhea, fever, stomatitis, esophagitis/dysphagia.
- Grade 3 nausea and vomiting uncontrolled by antiemetics; Grade 3 diarrhea uncontrolled by antidiarrheal agents; Grade 3 drug-induced fever uncontrolled by antipyretics.
- Grade 3 stomatitis and/or esophagitis/dysphagia lasting >3 days.
- Grade 4 neutropenia or thrombocytopenia lasting >5 days.
- Episode of neutropenic fever, as defined in Protocol.
- Failure to recover neutrophils (>1,500 per microliter) or platelets (>75,000 per microliter) by day 28.
Measured: 28 days after start of first administration of ON 01910.Na
Secondary outcomes (5)
Number of Adverse Events (AEs)
All adverse events (except grade 1 and 2 laboratory abnormalities that do not require an intervention), regardless of causal relationship, are recorded in the case report form and source documentation.
Measured: 30 days after last infusion of study drug
Severity of Adverse Events
Severity of AEs are determined according to the NCI Common Terminology Criteria for Adverse Events, Version 3.0.
Measured: 30 days after last infusion of study drug
Relationship of Adverse Events (AEs) to Study Treatment
Relationship assessed as Not related, Unlikely, Possibly, Probably, or, Definitely according to Guidance in Appendix II of Protocol.
Measured: 30 days after last infusion of study drug
Concentration of ON 01910.Na in plasma versus time
Blood samples for subsequent preparation of plasma and determination of concentration of ON 01910.Na will be collected at pre-dose at 1 hr, 3 hr, 6 hr, 24 hr, 48 hr and 72 hr (10 min, prior to completion of infusion). After the completion of the infusion, samples will be collected at 10 min, 20 min, 30 min, 1 hr, 2 hr, 4 hr, 8 hr, 24 hr, 48 hr, and 72 hr.
Measured: Up to 72 hours after end of infusion of study drug in Cycles 1 and 4
Change in size of target lesions recorded at baseline
The same method of assessment for each identified and recorded lesion will be used at baseline and each follow-up.
Measured: 30 days after last infusion of study drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2012 (estimated)
- Study startAug 2006
- Primary completionOct 2010
- Study completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Advanced 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Traws Pharma, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Takao Ohnuma, MD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01538537
- Sponsor's protocol ID
- Onconova 04-02
- Status last verified
- Jun 2017
- First submitted
- 20 Feb 2012
- Last updated
- 23 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Ohnuma T, Lehrer D, Ren C, Cho SY, Maniar M, Silverman L, Sung M, Gretz HF 3rd, Benisovich V, Navada S, Akahoho E, Wilck E, Taft DR, Roboz J, Wilhelm F, Holland JF. Phase 1 study of intravenous rigosertib (ON 01910.Na), a novel benzyl styryl sulfone structure producing G2/M arrest and apoptosis, in adult patients with advanced cancer. Am J Cancer Res. 2013 Jun 20;3(3):323-38. Print 2013.
PubMed 23841031Garcia-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 23 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Dose Escalation Study of ON 01910.Na by 3-day Continuous Infusion in Patients With Advanced Cancer
- ClinicalTrials.gov ID
- NCT01538537
- Acronym / sponsor ID
- Onconova 04-02
- Conditions
- Advanced Cancer, Solid Tumors, Cancer, Neoplasms
- Keywords
- ON 01910.Na, rigosertib Sodium, rigosertib
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Traws Pharma, Inc.Industry (pharma, biotech, devices)
- Study start
- Aug 2006
- Primary completion
- Oct 2010 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 24 Feb 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to determine the largest dose of ON 01910.Na (rigosertib sodium) that can be given safely as a 3-day continuous infusion once every 2 weeks (2-week cycle) in patients with advanced cancer.
Detailed description
This was an open-label, single-center, dose-escalating Phase I study to determine the Dose-Limiting Toxicities (DLTs) and Recommended Phase 2 Dose (RPTD) of ON 01910.Na (rigosertib sodium) administered as a 3 day continuous intravenous (CIV) infusion every 2 weeks (2-week cycles) to up to 28 patients with advanced cancer (12 to 16 in the dose escalation phase and up to 12 additional patients in the dose confirmation phase). The dosing of rigosertib was based on body surface area (BSA), with a starting dose of 50 mg/m2/24 hour for 3 consecutive days.
In the absence of toxicity after at least a 3-week observation period, rigosertib doses were escalated following a Fibonacci scheme with an initial accelerated dose-escalation phase in which 1-patient cohorts received rigosertib for 3 weeks until drug-related Grade 2 toxicity (according to Common Toxicity Criteria for Adverse Events [CTCAE] v.3), excluding alopecia, occurred, at which time 2 additional patients were added to subsequent cohorts. If none of the 3 patients in the cohort experienced DLTs, the dose was escalated by a half-Fibonacci step. If a DLT was seen in the first patient of a cohort, dosing went back a half-step. The next dose level occurred if no DLT was reported in the 3 patients or if no more than 1 DLT occurred in an expanded cohort of 6 patients. If a DLT was seen in 1 of the 3 patients, 3 additional patients were enrolled in the cohort. If DLTs were seen in 2 of 6 patients in a cohort, dose escalation was stopped.
Once the maximum administered dose (MAD) was attained and the RPTD was determined, the dose escalation phase was considered complete. Up to 12 additional patients with histologically confirmed malignant tumors were tested at the RPTD dose to confirm its appropriateness.
Secondary objectives were to determine the qualitative and quantitative toxicity and reversibility of toxicity of rigosertib administered in this fashion; to investigate the clinical pharmacology of rigosertib when administered in this fashion, including plasma pharmacokinetics at each dose level; to confirm the appropriateness of the RPTD; to document any observed antitumor activity of rigosertib; and, to evaluate the biological effect of rigosertib in biomarkers in serum and/or peripheral blood mononuclear cells.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Patient must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.
- At least 4 weeks since the last dose of other potentially myelosuppressive treatment (at least 6 weeks since last dose of nitrosoureas or mitomycin C) and recovery from manifestations of reversible drug toxicity (except alopecia, stable residual neuropathy, and residual hand and foot syndrome). Among patients with prior doxorubicin chemotherapy, only those with no more than 450 mg/m2 of the drug will be entered. It must be at least 4 weeks since prior chemotherapy or radiation therapy, 6 weeks if the last regimen included nitrosoureas or mitomycin C.
- Patients with prior radiotherapy are eligible provided that a minimum of 4 weeks have passed and that the maximal area of hematopoietic active bone marrow treated was less than 25%.
- ECOG performance status < 2.
- Hgb > 10 gm/dl
Key exclusion criteria (8 listed)
- Patients who have had recent major surgery (within the past 14 days), chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (except alopecia, stable residual neuropathy, and residual hand and foot syndrome) due to previously administered agents.
- Patients may not be receiving any other investigational agents or concurrent chemotherapy, radiotherapy, hormonal treatments, or immunotherapy while on study.
- Patients with known or clinical evidence of central nervous system metastasis, except brain metastases that have been previously removed or irradiated and currently have no clinical impact.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ON 01910.Na.
- The patient should have no major 3rd space fluid, ascites requiring active medical management including paracentesis, peripheral bilateral edema, or hyponatremia (serum sodium value less than 134 Meq/L).
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 |
|---|---|---|
| rigosertib sodiumAlso: ON 01910.Na Concentrate, ON 01910.Na, rigosertibON 01910.Na will be supplied as a sterile, concentrated solution (75 mg/ml) in labeled, sealed glass vials. ON 01910.Na concentrated solution (75 mg/ml) must be diluted before intravenous administration. The starting dose will be 50 mg/m2 over 24 hour infusion daily for 3 days. A fresh infusion must be prepared for each day of the 3-day continuous infusion. This 3-day continuous treatment followed by 11 days without administration of study drug will constitute 1 Cycle. Cycles can be repeated every 2 weeks. The dosing of ON 01910.Na will be based on body surface area (BSA). In the absence of toxicity that would cause accelerated dose escalation to cease, drug doses are planned to escalate every 3 weeks. | Drug | – |
Primary outcome
Number of dose limiting toxicities (DLTs)
Time frame: 28 days after start of first administration of ON 01910.Na
DLTs are defined as: * Grade 3 non-hematological toxicity other than nausea, vomiting, diarrhea, fever, stomatitis, esophagitis/dysphagia. * Grade 3 nausea and vomiting uncontrolled by antiemetics; Grade 3 diarrhea uncontrolled by antidiarrheal agents; Grade 3 drug-induced fever uncontrolled by antipyretics. * Grade 3 stomatitis and/or esophagitis/dysphagia lasting >3 days. * Grade 4 neutropenia or thrombocytopenia lasting >5 days. * Episode of neutropenic fever, as defined in Protocol. * Failure to recover neutrophils (>1,500 per microliter) or platelets (>75,000 per microliter) by day 28.
5 secondary outcomes
Number of Adverse Events (AEs)
Time frame: 30 days after last infusion of study drug
Severity of Adverse Events
Time frame: 30 days after last infusion of study drug
Relationship of Adverse Events (AEs) to Study Treatment
Time frame: 30 days after last infusion of study drug
Concentration of ON 01910.Na in plasma versus time
Time frame: Up to 72 hours after end of infusion of study drug in Cycles 1 and 4
Change in size of target lesions recorded at baseline
Time frame: 30 days after last infusion of study drug
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2017.
- Results publication: PubMed 23841031Ohnuma T, Lehrer D, Ren C, Cho SY, Maniar M, Silverman L, Sung M, Gretz HF 3rd, Benisovich V, Navada S, Akahoho E, Wilck E, Taft DR, Roboz J, Wilhelm F, Holland JF. Phase 1 study of intravenous rigosertib (ON 01910.Na), a novel benzyl styryl sulfone structure producing G2/M arrest and apoptosis, in adult patients with advanced cancer. Am J Cancer Res. 2013 Jun 20;3(3):323-38. Print 2013.
- 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.
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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.
Takao Ohnuma, MD principal investigator
Icahn School of Medicine at Mount Sinai
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing rigosertib sodium in people with Advanced Cancer and Solid Tumors, 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 14 inclusion and 8 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 23 Jun 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Number of dose limiting toxicities (DLTs) (time frame: 28 days after start of first administration of ON 01910.Na). 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 NCT01538537, which also lists 2 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 23 Jun 2017.