Solid TumorPhase 1NCT01168011
Safety, Pharmacokinetics and Clinical Activity of Oral Rigosertib in Solid Tumors
A Phase 1 study testing rigosertib in people with Solid Tumor, run by Traws Pharma, Inc. at 1 site in United States.
Trial summary
This is a phase 1 study in which 2 to 72 patients with advanced cancer will receive oral doses of rigosertib, a new investigational (unapproved) anti-cancer drug. The objective of the study is to determine the highest dose of drug that can be given safely. The study will start by testing a low dose. 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?
- rigosertib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2010to Dec 2015
- 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
- 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.
- ECOG performance status 2, 1 or 0.
- Life expectancy greater than 6 months.
- One or more measurable lesion(s) ("target lesion[s]"), that can be accurately measured in at least 1 dimension with longest diameter equal to or greater than 20 mm using conventional techniques (computed tomography [CT] scan or magnetic resonance imaging [MRI]) or equal to or greater than 10 mm with spiral CT scan.
- If female, has a negative screening for pregnancy. Women of child-bearing potential and men must agree to use adequate contraception prior to study entry (hormonal or barrier method of birth control; abstinence) and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
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- Ability to understand the nature of the study and any hazards of participating in it, to communicate satisfactorily with the investigator, and to participate in, and comply with, the requirements of the entire study.
- Willing to adhere to the prohibitions and restrictions specified in this protocol.
- Patient must have signed an informed consent document.
Who cannot join
- Recent major surgery (within the past 14 days).
- Chemotherapy or dose of other potentially myelosuppressive treatment within 3 weeks prior to entering the study (6 weeks for nitrosoureas or mitomycin C).
- Among patients with prior doxorubicin chemotherapy, only those with no more than a total cumulative dose of 450 mg/m2 of the drug.
- Definitive radiotherapy (over 10 fractions and maximal area of hematopoietic active bone marrow treated was greater than 25%) within 4 weeks prior to entering the study.
- Palliative radiotherapy (10 or less fractions) within 2 weeks prior to entering the study.
- Residual adverse events (except alopecia, stable residual neuropathy, and residual hand, foot syndrome) and ascites requiring active medical management including paracentesis, peripheral bilateral edema, hyponatremia (serum value less than 130 Meq/L) due to previously administered agents, which have not recovered at grade 1 severity level or below before study entry.
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- Receiving any other investigational agents or concurrent chemotherapy, radiotherapy, hormonal treatments, bone marrow transplantation, or immunotherapy while on study. Exceptions are long-term hormonals for prostate (e.g. goserelin) and octreotide for neuroendocrine malignancies.
- Previous bone marrow transplant.
- 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.
- Hgb less than 9 gm/dL (must not require transfusional support but erythropoietin therapy is permitted).
- WBC less than 4,000/microliter.
- Absolute neutrophil count less than 1,500/microliter.
- Platelets less than or equal to 100,000/microliter.
- Total bilirubin greater than 1.5 times institutional upper normal limit.
- AST(SGOT)/ALT(SGPT) equal to or greater than 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.).
- Serum creatinine greater than 2 times upper limit of institutional normal value.
- Pregnant and nursing women.
- HIV-1 positive patients receiving combination anti-retroviral therapy.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado at Denver Health and Sciences
Denver, Colorado, 80045
About this study
Official title: A Phase 1 Study To Assess The Tolerability, Pharmacokinetics and Clinical Activity of Rigosertib Administered Orally as Escalating Multiple Doses Twice or Three Times a Day up to 21 Days of a 21-Day Cycle in Patients With Advanced Cancer
This is a phase 1 study in which 2 to 72 patients with advanced cancer will receive oral doses of rigosertib, a new investigational (unapproved) anti-cancer drug. The objective of the study is to determine the highest dose of drug that can be given safely. The study will start by testing a low dose. If this dose is safe, then, higher and higher doses will be tested as long as the previous lower dose was safe. Safety will be determined by looking for any side effects or unusual laboratory values. It is important to know the highest safe dose so that additional studies can be done. The drug will be given in the form of capsules twice or three times a day for 21 consecutive days of 21-day cycles.
Read the detailed description
Patients will be initially enrolled in two-patient cohorts starting with a 70 mg bid dosing.
- In the absence of drug-related grade 2 or higher toxicity in the two patients treated for an entire 21-day first cycle, the next two patients will be receiving a dose escalated by 100% from prior dose.
- If drug-related grade 2 or higher toxicity is observed in at least one of the two patients treated for a full 21-day cycle, the cohort will be expanded in order to obtain 3 evaluable (treated for an entire 21-day first cycle) patients.
- If no dose limiting toxicity (DLT) is observed in the first three patients treated for an entire 21-day first cycle, then the next three patients will be enrolled at a dose level increased by approximately 50% from prior dose.
- If one DLT is observed in the first three patients treated for an entire 21-day first cycle, then the three next patients will be enrolled at the same dose level.
- If no more than one DLT is observed in the six patients treated for an entire 21-day cycle, then the next six patients will be administered a dose level increased by approximately 25% from prior dose.
- If two or more patients in any cohort experience DLT, then the maximum tolerated dose (MTD) will have been exceeded and no further dose escalation will occur. The MTD will be established as the immediate prior dosing level
- Identical rules will be applied to all cohorts of patients recruited to the study.
- A total of up to 24 patients may be treated at the MTD dose level in order to obtain data on the onset and severity of dysuria symptoms in approximately 12 patients including about 6 patients who will be treated with oral sodium bicarbonate at the time of treatment initiation (early treatment) and ~6 patients who will be treated with oral sodium bicarbonate at the time of symptom onset (late treatment). Alternating patients on a 1-to-1 basis by enrollment date will receive oral sodium bicarbonate as 650 mg tablets given twice daily with two 8-ounce glasses of water 1 hour after rigosertib administration, either at the time of study initiation (early treatment) or at the time of urinary symptom onset (late treatment).
Three additional cohorts will be treated with multiple escalating doses administered orally three time daily (TID) (140 mg, 280 mg and 420 mg) for 21 consecutive days of a 21-day cycle using identical rules as those described above (ie, starting with 2-patient cohorts at 140 mg dosing and expanding to 3-6 patient cohorts if at least 1 Grade 2 or higher drug-related toxicity is observed in 2-patient cohorts).
Up to 12 patients may be treated at the MTD level identified with TID dosing.
Prior to escalating to the next planned dose level, a designated Cohort Review Committee (CRC) consisting of the Principal Investigators (or their representatives), the Medical Monitor and the Sponsor's Medical Representative will review all available safety data over the 21 day duration of Course 1 for the previous cohort. Additional input may be provided from the study monitors, pharmacokinetic or toxicology specialists as required. The CRC also has to ability to recommend dose de-escalation for ON 01910.Na if warranted by the observed toxicity profile.
- Conditions
- Solid Tumor
- Being tested
- rigosertib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rigosertibDrug
Also called rigosertib sodium, ON 01910.Na
Doses of rigosertib up to 700 mg twice a day or three times a day for 21 days of 21-day cycles. Treatment may continue until progression.
| Study group | Role | What they receive |
|---|---|---|
| rigosertib | Experimental | Doses of rigosertib up to 700 mg twice a day or three times a day every day of 21-day cycles. Receives: Drug: rigosertib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events
Adverse events (AEs) will be regarded as treatment emergent signs and symptoms (TESS) if they started on or after the date and time of administration of the first dose of study drug, or if they were present prior to the administration of the first dose of study drug and increased in severity during the study. Adverse events include clinical laboratory parameters (e.g., Hematology Panel and Serum Chemistry Panel). Other safety parameters include vital signs, physical examination findings, concomitant medications, and drug exposure.
Measured: 2 years
Secondary outcomes (3)
Concentration of ON 01910.Na in plasma
The concentration of ON 01910.Na in plasma at various times after administration will be used to derive the following PK parameters for ON 01910.Na using model-independent analysis as appropriate for the data: Tmax, Cmax, t½, AUC0-t, AUC 0-α, CL, and Vss.
Measured: 2 years
Measurement of tumor size
Tumor response rates will be evaluated for each patient using RECIST criteria.
Measured: 2 years
Concentration of ON 01910.Na in Urine
Urine PK samples to determine ON 01910.Na urinary concentrations will be collected on Day 1 and Day 21 of the first cycle, and on Day 15 of the second cycle in all patients and will include the predose void volume and a 24-hr post-dose urine collection over the 0-4 hr, 4-8 hr, and 8-24 hr intervals.
Measured: 1 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2010 (estimated)
- Study startJul 2010
- Primary completionDec 2015
- Study completionDec 2015
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
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- Traws Pharma, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Antonio Jimeno, MD, PhD, Principal investigator, University of Colorado at Denver Health and Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01168011
- Sponsor's protocol ID
- Onconova 09-04
- Other IDs
- COMIRB # 10-0150
- Status last verified
- Jun 2017
- First submitted
- 18 Jul 2010
- Last updated
- 23 Jun 2017
- Results posted
- No
- Data monitoring committee
- Yes
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
- A Phase 1 Study To Assess The Tolerability, Pharmacokinetics and Clinical Activity of Rigosertib Administered Orally as Escalating Multiple Doses Twice or Three Times a Day up to 21 Days of a 21-Day Cycle in Patients With Advanced Cancer
- ClinicalTrials.gov ID
- NCT01168011
- Acronym / sponsor ID
- Onconova 09-04
- Conditions
- Solid Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- Traws Pharma, Inc.Industry (pharma, biotech, devices)
- Study start
- Jul 2010
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 22 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.
This is a phase 1 study in which 2 to 72 patients with advanced cancer will receive oral doses of rigosertib, a new investigational (unapproved) anti-cancer drug. The objective of the study is to determine the highest dose of drug that can be given safely. The study will start by testing a low dose. If this dose is safe, then, higher and higher doses will be tested as long as the previous lower dose was safe. Safety will be determined by looking for any side effects or unusual laboratory values. It is important to know the highest safe dose so that additional studies can be done. The drug will be given in the form of capsules twice or three times a day for 21 consecutive days of 21-day cycles.
Detailed description
Patients will be initially enrolled in two-patient cohorts starting with a 70 mg bid dosing.
- In the absence of drug-related grade 2 or higher toxicity in the two patients treated for an entire 21-day first cycle, the next two patients will be receiving a dose escalated by 100% from prior dose.
- If drug-related grade 2 or higher toxicity is observed in at least one of the two patients treated for a full 21-day cycle, the cohort will be expanded in order to obtain 3 evaluable (treated for an entire 21-day first cycle) patients.
- If no dose limiting toxicity (DLT) is observed in the first three patients treated for an entire 21-day first cycle, then the next three patients will be enrolled at a dose level increased by approximately 50% from prior dose.
- If one DLT is observed in the first three patients treated for an entire 21-day first cycle, then the three next patients will be enrolled at the same dose level.
- If no more than one DLT is observed in the six patients treated for an entire 21-day cycle, then the next six patients will be administered a dose level increased by approximately 25% from prior dose.
- If two or more patients in any cohort experience DLT, then the maximum tolerated dose (MTD) will have been exceeded and no further dose escalation will occur. The MTD will be established as the immediate prior dosing level
- Identical rules will be applied to all cohorts of patients recruited to the study.
- A total of up to 24 patients may be treated at the MTD dose level in order to obtain data on the onset and severity of dysuria symptoms in approximately 12 patients including about 6 patients who will be treated with oral sodium bicarbonate at the time of treatment initiation (early treatment) and ~6 patients who will be treated with oral sodium bicarbonate at the time of symptom onset (late treatment). Alternating patients on a 1-to-1 basis by enrollment date will receive oral sodium bicarbonate as 650 mg tablets given twice daily with two 8-ounce glasses of water 1 hour after rigosertib administration, either at the time of study initiation (early treatment) or at the time of urinary symptom onset (late treatment).
Three additional cohorts will be treated with multiple escalating doses administered orally three time daily (TID) (140 mg, 280 mg and 420 mg) for 21 consecutive days of a 21-day cycle using identical rules as those described above (ie, starting with 2-patient cohorts at 140 mg dosing and expanding to 3-6 patient cohorts if at least 1 Grade 2 or higher drug-related toxicity is observed in 2-patient cohorts).
Up to 12 patients may be treated at the MTD level identified with TID dosing.
Prior to escalating to the next planned dose level, a designated Cohort Review Committee (CRC) consisting of the Principal Investigators (or their representatives), the Medical Monitor and the Sponsor's Medical Representative will review all available safety data over the 21 day duration of Course 1 for the previous cohort. Additional input may be provided from the study monitors, pharmacokinetic or toxicology specialists as required. The CRC also has to ability to recommend dose de-escalation for ON 01910.Na if warranted by the observed toxicity profile.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| rigosertib | Experimental | Drug: rigosertibDoses of rigosertib up to 700 mg twice a day or three times a day every day of 21-day cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
- ECOG performance status 2, 1 or 0.
- Life expectancy greater than 6 months.
- One or more measurable lesion(s) ("target lesion[s]"), that can be accurately measured in at least 1 dimension with longest diameter equal to or greater than 20 mm using conventional techniques (computed tomography [CT] scan or magnetic resonance imaging [MRI]) or equal to or greater than 10 mm with spiral CT scan.
Key exclusion criteria (20 listed)
- Recent major surgery (within the past 14 days).
- Chemotherapy or dose of other potentially myelosuppressive treatment within 3 weeks prior to entering the study (6 weeks for nitrosoureas or mitomycin C).
- Among patients with prior doxorubicin chemotherapy, only those with no more than a total cumulative dose of 450 mg/m2 of the drug.
- Definitive radiotherapy (over 10 fractions and maximal area of hematopoietic active bone marrow treated was greater than 25%) within 4 weeks prior to entering the study.
- Palliative radiotherapy (10 or less fractions) within 2 weeks prior to entering the study.
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 |
|---|---|---|
| rigosertibAlso: rigosertib sodium, ON 01910.NaDoses of rigosertib up to 700 mg twice a day or three times a day for 21 days of 21-day cycles. Treatment may continue until progression. | Drug | rigosertib |
Primary outcome
Adverse Events
Time frame: 2 years
Adverse events (AEs) will be regarded as treatment emergent signs and symptoms (TESS) if they started on or after the date and time of administration of the first dose of study drug, or if they were present prior to the administration of the first dose of study drug and increased in severity during the study. Adverse events include clinical laboratory parameters (e.g., Hematology Panel and Serum Chemistry Panel). Other safety parameters include vital signs, physical examination findings, concomitant medications, and drug exposure.
3 secondary outcomes
Concentration of ON 01910.Na in plasma
Time frame: 2 years
Measurement of tumor size
Time frame: 2 years
Concentration of ON 01910.Na in Urine
Time frame: 1 years
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.
- Clinical Trials at University of Colorado HospitalLink provided by the sponsor.
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A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
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A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
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IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
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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.
Antonio Jimeno, MD, PhD principal investigator
University of Colorado at Denver Health and Sciences
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 in people with Solid Tumor, 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 9 inclusion and 20 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?
Adverse Events (time frame: 2 years). 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 NCT01168011, 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.