Solid TumorPhase 1NCT01165905
Safety of 24-hour Infusion of ON 01910.Na in Combination With Gemcitabine in Advanced Solid Tumors
A Phase 1 study testing ON 01910.Na and Gemcitabine in people with Solid Tumor, run by Traws Pharma, Inc. at 2 sites in United States.
Trial summary
Treatment of cancer is often more effective when two or more drugs are used together. For example, when gemcitabine, an approved drug, and ON 01910.Na, a new investigational anti-cancer drug, are used together to treat cancer cells in laboratory animals, there is more inhibition of the growth of the cancer cells… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor
- What is being tested?
- ON 01910.Na and Gemcitabine
- Type of treatment
- Injection or infusion
- How many people
- 10 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2010to Jul 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
- Patients with histologically confirmed solid malignancy for which standard curative or palliative measures do not exist or are no longer effective; or patients with a clinical rationale for a gemcitabine-based therapy.
- The last radiotherapy/chemotherapy dose must have been given ≥4 weeks prior to study drug initiation; with any acute or chronic adverse events of prior radiotherapy or chemotherapy having resolved to <Grade 2 as determined by CTCAE v3.0 (Appendix IV).
- Patients must have a life expectancy of at least 12 weeks and an ECOG performance status of <1 (Appendix I).
- Patients must be >18 years of age.
- Patients must have evaluable disease, either with informative tumor markers or with measurable disease on imaging by RECIST (Response Evaluation Criteria in Solid Tumors) criteria (Appendix II).
- Patients must have adequate liver and renal function as defined by serum creatinine no greater than 2.0 times the institution's upper normal limits (or a 24 hour creatinine clearance of >50 ml/min) and total bilirubin level no greater than 2.0 times the institution's upper normal limits and transaminase levels no higher than 3.0 times the institution's upper normal limits. (Note that patients with primary liver cancer or hepatic metastases may have transaminase levels of up to 5.0 times the limit of normal).
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- Patients must have adequate bone marrow function as defined by a granulocyte count of >1,500/mm3, platelet count of >100,000/mm3, and hemoglobin >9 g/dl.
- Patients at the expanded phase at the MTD must be willing and able to undergo blood sampling for pharmacokinetic studies in Course 1.
- For patients in the expanded phase at the MTD, tumor amenable to a single tumor biopsy, and willingness to undergo a baseline tumor biopsy.
- Patients must sign an informed consent form indicating that they are aware of the investigational nature of this study and in keeping with the policies of the institution.
Who cannot join
- Patients will be excluded if they have evidence of active heart disease including myocardial infarction within the previous 3 months; symptomatic coronary insufficiency or heart block; uncontrolled congestive heart failure; moderate or severe pulmonary dysfunction.
- Patients will be excluded if they have an active infectious process.
- Patients will be excluded if they have active central nervous system metastases.
- Patients will be excluded if they have received prior radiotherapy administered to more than 30% of marrow-bearing bone mass.
- Patients will be excluded if they have ascites requiring active medical management including paracentesis for more than twice a month or hyponatremia (defined as serum sodium value of <134 Meq/L).
- Patients will be excluded if they are women who are pregnant or lactating.
- Patients will be excluded if they are male patients with female sexual partners who are unwilling to follow the strict contraception requirements described in this protocol.
- Patients will be excluded if they have had major surgery without full recovery or major surgery within 3 weeks of ON 01910.Na treatment start.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Department of Medicine, University of California San Francisco
San Francisco, California, 94143
Albert Einstein Cancer Center/Montefiore Medical Center
The Bronx, New York, 10461
About this study
Official title: Phase I Dose Escalation Study of Gemcitabine and 24 Hour Infusion of ON 01910.Na in Patients With Advanced or Metastatic Solid Tumors
Treatment of cancer is often more effective when two or more drugs are used together. For example, when gemcitabine, an approved drug, and ON 01910.Na, a new investigational anti-cancer drug, are used together to treat cancer cells in laboratory animals, there is more inhibition of the growth of the cancer cells compared to either drug used by itself. These results offer promise that gemcitabine and ON 01910.Na could be used to treat cancer in patients. However, before studies that seek to find out if gemcitabine and ON 01910.Na is an effective combination in patients can be done, doctors must first know what is largest, safe dose of ON 01910.Na that can be used in combination with gemcitabine and what is the best regimen to use. This study is designed to answer that question.
Read the detailed description
The order of infusion will be gemcitabine first, immediately followed by ON 01910.Na (with the only exception being the first infusion for those patients undergoing PK sampling; where the ON 01910.Na infusion will be given first on this occasion). The dose of gemcitabine will be fixed at 1000 mg/m2 i.v. as a 30 minutes infusion on days 1, 8, and 15 every 28 days. As of Amendment 2, the starting dose of ON 01910.Na is 250 mg/m2 as a 24 hour intravenous (i.v.) infusion on days 1, 8 and 15 of a 28-day course. The dose of ON 01910.Na will be escalated in increments in successive cohorts (dose level (DL) 1 = 250 mg/m2, DL 2 = 650 mg/m2, DL 3 = 1050 mg/m2, DL 4= 1350 mg/m2) of new patients. A course is defined as 4 weeks in length. Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v3.0). A minimum of three new patients will be treated at each dose level with a minimum of a 1 week stagger between the dosing of the first and remaining patients in each new dose cohort. In exceptional circumstances (e.g. where there is one slot available in a cohort and two eligible patients have been screened), the Sponsor may allow four patients to enter a cohort (or seven patients to enter an expanded cohort). A DL -1A (ON 01910.Na = 125 mg/m2) is set in case dose de-escalation is required with the starting dose due to ON 01910.Na-related toxicity. A DL -1A gemcitabine = 750 mg/m2 and DL - 1B at 500 mg/m2 are set in case dose de-escalation is required with the starting and subsequent doses due to gemcitabine-related toxicity. If DLT is not observed in the first three patients, then the dose of ON 01910.Na will be increased to the next level. If DLT occurs in any of the first three new patients in the first course, at least three additional new patients will be treated. If no further DLT is encountered, dose escalation will proceed. Alternately, if DLT is noted in one or more of three additional patients, dose escalation will be terminated and the MTD will be defined as the highest dose level at which none of the first three patients or no more than one of six patients experienced DLT in course 1. All patients receiving doses exceeding the confirmed MTD will have their dose reduced to the MTD; even if apparently tolerating their current dose. Intra-patient dose escalation of ON 01910.Na will be permitted. There will be no limit to the number of courses that could be administered to a patient who is both tolerating and benefiting from therapy.
Escalation to the next dose level will occur only after the third evaluable patient (or sixth, if an expanded cohort), on the previous dose level has been observed for 4 weeks. Dose escalation decisions will be made by a Cohort Review Committee (CRC). Intra-patient dose escalation of ON 01910.Na will be allowed after the third evaluable patient on the next dose level has been observed for 4 weeks with acceptable tolerability.
Once the MTD has been defined, an expanded cohort of 9 to 12 additional patients (depending if 3 or 6 patients were enrolled on the previous cohort) will be enrolled at the MTD dose level in order to further define the safety and tolerability of this regimen, and characterize the pharmacokinetics of ON 01910.Na alone and after gemcitabine, and perform a tumor biomarker study.
- Conditions
- Solid Tumor
- Being tested
- ON 01910.Na, Gemcitabine
- Keywords
- cancer, solid malignancy, tumor, malignant neoplasm, histologically confirmed solid malignancy
- Medical subject headings
- 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 sodium
The starting dose of ON 01910.Na is 250 mg/m2 as a 24 hour intravenous (i.v.) infusion on days 1, 8 and 15 of a 28-day course. The dose of ON 01910.Na will be escalated in increments in successive cohorts (dose level (DL) 1 = 250 mg/m2, DL 2 = 650 mg/m2, DL 3 = 1050 mg/m2, DL 4= 1350 mg/m2) of new patients. A course is defined as 4 weeks in length.
GemcitabineDrug
Also called Gemzar, gemcitabine HCl, 2´-deoxy-2´,2´-difluorocytidine monohydrochloride (-isomer), gemcitabine for injection, USP
The dose of gemcitabine will be fixed at 1000 mg/m2 i.v. as a 30 minutes infusion on days 1, 8, and 15 every 28 days.
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events and Laboratory Parameters
Incidence of adverse signs and/or symptoms (adverse events and laboratory parameters)
Measured: Throughout study
Secondary outcomes (1)
Pharmacokinetics
The derived plasma pharmacokinetic parameters of ON 01910.Na administered alone and with gemcitabine at the MTD will also be investigated: Cmax, tmax, terminal half-life, AUC0-last, AUC0-inf., CL, and Vss.
Measured: MTD confirmation phase of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2010 (estimated)
- Study startJan 2010
- Primary completionJul 2011
- Study completionJul 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 TumorStudies 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
- 10 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 MedicinePamela N. Munster, MD, Principal investigator, Department of Medicine, University of California San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01165905
- Sponsor's protocol ID
- Onconova 04-10
- Status last verified
- Jun 2017
- First submitted
- 18 Jul 2010
- 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 Gemcitabine and 24 Hour Infusion of ON 01910.Na in Patients With Advanced or Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT01165905
- Acronym / sponsor ID
- Onconova 04-10
- Conditions
- Solid Tumor
- Keywords
- cancer, solid malignancy, tumor, malignant neoplasm, histologically confirmed solid malignancy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Traws Pharma, Inc.Industry (pharma, biotech, devices)
- Study start
- Jan 2010
- Primary completion
- Jul 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 20 Jul 2010 (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.
Treatment of cancer is often more effective when two or more drugs are used together. For example, when gemcitabine, an approved drug, and ON 01910.Na, a new investigational anti-cancer drug, are used together to treat cancer cells in laboratory animals, there is more inhibition of the growth of the cancer cells compared to either drug used by itself. These results offer promise that gemcitabine and ON 01910.Na could be used to treat cancer in patients. However, before studies that seek to find out if gemcitabine and ON 01910.Na is an effective combination in patients can be done, doctors must first know what is largest, safe dose of ON 01910.Na that can be used in combination with gemcitabine and what is the best regimen to use. This study is designed to answer that question.
Detailed description
The order of infusion will be gemcitabine first, immediately followed by ON 01910.Na (with the only exception being the first infusion for those patients undergoing PK sampling; where the ON 01910.Na infusion will be given first on this occasion). The dose of gemcitabine will be fixed at 1000 mg/m2 i.v. as a 30 minutes infusion on days 1, 8, and 15 every 28 days. As of Amendment 2, the starting dose of ON 01910.Na is 250 mg/m2 as a 24 hour intravenous (i.v.) infusion on days 1, 8 and 15 of a 28-day course. The dose of ON 01910.Na will be escalated in increments in successive cohorts (dose level (DL) 1 = 250 mg/m2, DL 2 = 650 mg/m2, DL 3 = 1050 mg/m2, DL 4= 1350 mg/m2) of new patients. A course is defined as 4 weeks in length. Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v3.0). A minimum of three new patients will be treated at each dose level with a minimum of a 1 week stagger between the dosing of the first and remaining patients in each new dose cohort. In exceptional circumstances (e.g. where there is one slot available in a cohort and two eligible patients have been screened), the Sponsor may allow four patients to enter a cohort (or seven patients to enter an expanded cohort). A DL -1A (ON 01910.Na = 125 mg/m2) is set in case dose de-escalation is required with the starting dose due to ON 01910.Na-related toxicity. A DL -1A gemcitabine = 750 mg/m2 and DL - 1B at 500 mg/m2 are set in case dose de-escalation is required with the starting and subsequent doses due to gemcitabine-related toxicity. If DLT is not observed in the first three patients, then the dose of ON 01910.Na will be increased to the next level. If DLT occurs in any of the first three new patients in the first course, at least three additional new patients will be treated. If no further DLT is encountered, dose escalation will proceed. Alternately, if DLT is noted in one or more of three additional patients, dose escalation will be terminated and the MTD will be defined as the highest dose level at which none of the first three patients or no more than one of six patients experienced DLT in course 1. All patients receiving doses exceeding the confirmed MTD will have their dose reduced to the MTD; even if apparently tolerating their current dose. Intra-patient dose escalation of ON 01910.Na will be permitted. There will be no limit to the number of courses that could be administered to a patient who is both tolerating and benefiting from therapy.
Escalation to the next dose level will occur only after the third evaluable patient (or sixth, if an expanded cohort), on the previous dose level has been observed for 4 weeks. Dose escalation decisions will be made by a Cohort Review Committee (CRC). Intra-patient dose escalation of ON 01910.Na will be allowed after the third evaluable patient on the next dose level has been observed for 4 weeks with acceptable tolerability.
Once the MTD has been defined, an expanded cohort of 9 to 12 additional patients (depending if 3 or 6 patients were enrolled on the previous cohort) will be enrolled at the MTD dose level in order to further define the safety and tolerability of this regimen, and characterize the pharmacokinetics of ON 01910.Na alone and after gemcitabine, and perform a tumor biomarker study.
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 (10 listed)
- Patients with histologically confirmed solid malignancy for which standard curative or palliative measures do not exist or are no longer effective; or patients with a clinical rationale for a gemcitabine-based therapy.
- The last radiotherapy/chemotherapy dose must have been given ≥4 weeks prior to study drug initiation; with any acute or chronic adverse events of prior radiotherapy or chemotherapy having resolved to <Grade 2 as determined by CTCAE v3.0 (Appendix IV).
- Patients must have a life expectancy of at least 12 weeks and an ECOG performance status of <1 (Appendix I).
- Patients must be >18 years of age.
- Patients must have evaluable disease, either with informative tumor markers or with measurable disease on imaging by RECIST (Response Evaluation Criteria in Solid Tumors) criteria (Appendix II).
Key exclusion criteria (8 listed)
- Patients will be excluded if they have evidence of active heart disease including myocardial infarction within the previous 3 months; symptomatic coronary insufficiency or heart block; uncontrolled congestive heart failure; moderate or severe pulmonary dysfunction.
- Patients will be excluded if they have an active infectious process.
- Patients will be excluded if they have active central nervous system metastases.
- Patients will be excluded if they have received prior radiotherapy administered to more than 30% of marrow-bearing bone mass.
- Patients will be excluded if they have ascites requiring active medical management including paracentesis for more than twice a month or hyponatremia (defined as serum sodium value of <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 |
|---|---|---|
| ON 01910.NaAlso: rigosertib sodiumThe starting dose of ON 01910.Na is 250 mg/m2 as a 24 hour intravenous (i.v.) infusion on days 1, 8 and 15 of a 28-day course. The dose of ON 01910.Na will be escalated in increments in successive cohorts (dose level (DL) 1 = 250 mg/m2, DL 2 = 650 mg/m2, DL 3 = 1050 mg/m2, DL 4= 1350 mg/m2) of new patients. A course is defined as 4 weeks in length. | Drug | – |
| GemcitabineAlso: Gemzar, gemcitabine HCl, 2´-deoxy-2´,2´-difluorocytidine monohydrochloride (-isomer), gemcitabine for injection, USPThe dose of gemcitabine will be fixed at 1000 mg/m2 i.v. as a 30 minutes infusion on days 1, 8, and 15 every 28 days. | Drug | – |
Primary outcome
Adverse Events and Laboratory Parameters
Time frame: Throughout study
Incidence of adverse signs and/or symptoms (adverse events and laboratory parameters)
1 secondary outcome
Pharmacokinetics
Time frame: MTD confirmation phase of study
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
Pamela N. Munster, MD principal investigator
Department of Medicine, University of California San Francisco
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ON 01910.Na and Gemcitabine in people with Solid Tumor, run by Traws Pharma, Inc. at 2 sites 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 10 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 2 sites 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?
Adverse Events and Laboratory Parameters (time frame: Throughout study). 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 NCT01165905, 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.