Solid TumorsPhase 1NCT01538563
Safety of 24-Hour Infusion of ON 01910.Na in Patients With Advanced Cancer
A Phase 1 study testing rigosertib sodium in people with Solid Tumors and Advanced Cancer, run by Traws Pharma, Inc. at 1 site in United States.
Trial summary
The primary purpose of this study is to determine the highest dose of ON 01910.Na that can be safely given as an intravenous infusion over 24 hours once a week in a 3-week cycle to patients with advanced solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors, Advanced Cancer, Cancer
- What is being tested?
- rigosertib sodium
- Type of treatment
- Injection or infusion
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2006to Nov 2011
- 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
- Must have histologically confirmed solid tumor (leukemias and lymphomas excluded) malignancy that is incurable and for which standard (FDA approved or established standard clinical practice), curative, or palliative measures do not exist or are no longer effective.
- Patients with disease amenable to sequential biopsies will be requested to undergo two tumor biopsies and two normal skin biopsies, but patients may decline and still be eligible for enrollment during this escalation stage.
- At least 3 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 (alopecia, stable residual neuropathy, and residual hand and foot syndrome are excluded). Patients with prior doxorubicin chemotherapy must have total cumulative dose of no more than 450 mg/m2.
- Patients with prior radiotherapy are eligible provided a minimum of 4 weeks have passed and the maximal area of hematopoietic active bone marrow treated was less than 25%.
- ECOG performance status ≤2.
- Patients must have nearly normal organ and marrow function as defined below:
Show all 17Show fewer
- Hgb > 9 gm/dl (must not require transfusional support but erythropoietin therapy is permitted)
- WBC > 4,000 per microliter
- Absolute neutrophil count > 1,500 per microliter
- Platelets ≥ 100,000 per microliter
- Total bilirubin within 1.5 times institutional upper normal limit
- AST(SGOT)/ALT(SGPT) ≤ 2.5 x institutional upper normal limit. (If liver function abnormalities are due to metastatic disease, patients are eligible provided the transaminases are < 5 times institutional upper normal limit. Patients with primary liver disease with these parameters will be ineligible.)
- Serum creatinine within normal institutional limits or estimated 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 prior to study entry.
- Ability to understand and the willingness to sign a written informed consent document.
- All ethnic groups are eligible for this trial.
- 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
- Recent major surgery (within the past 14 days), chemotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) or radiotherapy within 4 weeks 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 on any other investigational agents or concurrent chemotherapy, radiotherapy, hormonal treatments, bone marrow transplantation, or immunotherapy. Patients who have previously had a Bone Marrow Transplant are excluded from this study.
- Known brain metastases, 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.
- 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.
- HIV-positive patients receiving combination anti-retroviral therapy are excluded.
- Ascites requiring active medical management including paracentesis, peripheral bilateral edema, hyponatremia (serum sodium value less than 134 Meq/L).
Trial locations and contacts
1 site in 1 country.
United States1 site
Albert Einstein Cancer Center
The Bronx, New York, 10461
About this study
Official title: Phase I Dose Escalation Study of ON 01910.Na by 24 Hour Continuous Infusion Per Week in Patients With Advanced Cancer
The primary purpose of this study is to determine the highest dose of ON 01910.Na that can be safely given as an intravenous infusion over 24 hours once a week in a 3-week cycle to patients with advanced solid tumors.
Read the detailed description
This is an open-label, dose-escalating Phase I study of ON 01910.Na in patients with advanced cancers, who have satisfied the inclusion/exclusion criteria enumerated in this protocol. Patients will receive ON 01910.Na intravenously by 24 hour continuous infusion once every week (3 weeks per cycle), until evidence of disease progression, intolerable adverse events, or withdrawal of patient consent. Safety monitoring will be done for at least 3 weeks before escalation to the next dose level. As of Amendment 7, up to 6 patients with gynecological malignancies will be enrolled at the 2400 mg/m2 dose level to determine the appropriateness of this dose as the Recommended Phase Two Dose (RPTD).
- Conditions
- Solid Tumors, Advanced Cancer, Cancer, Neoplasms
- Being tested
- rigosertib sodium
- Keywords
- ON 01910.Na, rigosertib sodium, rogosertib
- 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
Patients will receive escalating doses of ON 01910.Na (250 mg/m2 to 4450 mg/m2) intravenously by 24 hour continuous infusion once every week (3 weeks per cycle), until evidence of disease progression, intolerable adverse events, or withdrawal of patient consent.
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.
- Recurrent grade 3 toxicity uncontrolled by optimal therapy or Grade 4 nausea, vomiting, diarrhea and fever.
- Grade 3 stomatitis and/or esophagitis/dysphagia for > 5 days.
- Grade 4 neutropenia or thrombocytopenia for > 5 days measured at least 2X 2-3 days apart.
- Neutropenic fever, as defined in Protocol.
- Failure to recover neutrophils (> 1,500 per microliter) or platelets (>75,000 per microliter) before the next weekly dose.
Measured: 21 days after first administration of ON 01910.Na
Secondary outcomes (5)
Number of Adverse Events (AEs)
All AEs (except Grade 1 and 2 laboratories abnormalities that do not require an intervention) are recorded in Case Report Forms and source documentation.
Measured: 30 days after last infusion of study drug
Severity of Adverse Events (AEs)
Severity of AEs are determined according to 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 will be collected at following time points: Pre-dose; 1 h after start of infusion; 3 h; 6 h; 12 h; 18 h; 24 h; 10 min after end of infusion; 20 min; 30 min; 1 h; 2 h; 4 h; 8 h; 24 h; and, 48 h. Plasma will be prepared from these samples. Concentration of ON 01910.Na will be determined by validated method.
Measured: Up to 48 hours after infusion of study drug during Week 1 in Cycles 1 and 2
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 startJun 2006
- Primary completionJul 2010
- Study completionNov 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Solid TumorsStudies 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
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Traws Pharma, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sridhar Mani, MD, Principal investigator, Albert Einstein College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01538563
- Sponsor's protocol ID
- Onconova 04-03
- Status last verified
- Jun 2017
- First submitted
- 20 Feb 2012
- Last updated
- 23 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Garcia-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 24 Hour Continuous Infusion Per Week in Patients With Advanced Cancer
- ClinicalTrials.gov ID
- NCT01538563
- Acronym / sponsor ID
- Onconova 04-03
- Conditions
- Solid Tumors, Advanced Cancer, Cancer, Neoplasms
- Keywords
- ON 01910.Na, rigosertib sodium, rogosertib
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Traws Pharma, Inc.Industry (pharma, biotech, devices)
- Study start
- Jun 2006
- Primary completion
- Jul 2010 (actual)
- Study completion
- Nov 2011 (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 purpose of this study is to determine the highest dose of ON 01910.Na that can be safely given as an intravenous infusion over 24 hours once a week in a 3-week cycle to patients with advanced solid tumors.
Detailed description
This is an open-label, dose-escalating Phase I study of ON 01910.Na in patients with advanced cancers, who have satisfied the inclusion/exclusion criteria enumerated in this protocol. Patients will receive ON 01910.Na intravenously by 24 hour continuous infusion once every week (3 weeks per cycle), until evidence of disease progression, intolerable adverse events, or withdrawal of patient consent. Safety monitoring will be done for at least 3 weeks before escalation to the next dose level. As of Amendment 7, up to 6 patients with gynecological malignancies will be enrolled at the 2400 mg/m2 dose level to determine the appropriateness of this dose as the Recommended Phase Two Dose (RPTD).
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 (17 listed)
- Must have histologically confirmed solid tumor (leukemias and lymphomas excluded) malignancy that is incurable and for which standard (FDA approved or established standard clinical practice), curative, or palliative measures do not exist or are no longer effective.
- Patients with disease amenable to sequential biopsies will be requested to undergo two tumor biopsies and two normal skin biopsies, but patients may decline and still be eligible for enrollment during this escalation stage.
- At least 3 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 (alopecia, stable residual neuropathy, and residual hand and foot syndrome are excluded). Patients with prior doxorubicin chemotherapy must have total cumulative dose of no more than 450 mg/m2.
- Patients with prior radiotherapy are eligible provided a minimum of 4 weeks have passed and the maximal area of hematopoietic active bone marrow treated was less than 25%.
- ECOG performance status ≤2.
Key exclusion criteria (8 listed)
- Recent major surgery (within the past 14 days), chemotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) or radiotherapy within 4 weeks 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 on any other investigational agents or concurrent chemotherapy, radiotherapy, hormonal treatments, bone marrow transplantation, or immunotherapy. Patients who have previously had a Bone Marrow Transplant are excluded from this study.
- Known brain metastases, 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.
- 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.
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, rigosertibPatients will receive escalating doses of ON 01910.Na (250 mg/m2 to 4450 mg/m2) intravenously by 24 hour continuous infusion once every week (3 weeks per cycle), until evidence of disease progression, intolerable adverse events, or withdrawal of patient consent. | Drug | – |
Primary outcome
Number of dose limiting toxicities (DLTs)
Time frame: 21 days after first administration of ON 01910.Na
DLTs are defined as: * Grade 3 non-hematological toxicity other than nausea, vomiting, diarrhea, fever, stomatitis, esophagitis/dysphagia. * Recurrent grade 3 toxicity uncontrolled by optimal therapy or Grade 4 nausea, vomiting, diarrhea and fever. * Grade 3 stomatitis and/or esophagitis/dysphagia for > 5 days. * Grade 4 neutropenia or thrombocytopenia for > 5 days measured at least 2X 2-3 days apart. * Neutropenic fever, as defined in Protocol. * Failure to recover neutrophils (> 1,500 per microliter) or platelets (>75,000 per microliter) before the next weekly dose.
5 secondary outcomes
Number of Adverse Events (AEs)
Time frame: 30 days after last infusion of study drug
Severity of Adverse Events (AEs)
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 48 hours after infusion of study drug during Week 1 in Cycles 1 and 2
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 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.
Sridhar Mani, MD principal investigator
Albert Einstein College of Medicine
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 Solid Tumors and Advanced 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 17 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: 21 days after 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 NCT01538563, which also lists 1 linked publication.
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.