- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01165905
Safety of 24-hour Infusion of ON 01910.Na in Combination With Gemcitabine in Advanced Solid Tumors
Phase I Dose Escalation Study of Gemcitabine and 24 Hour Infusion of ON 01910.Na in Patients With Advanced or Metastatic Solid Tumors
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
California
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San Francisco, California, United States, 94143
- Department of Medicine, University of California San Francisco
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New York
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The Bronx, New York, United States, 10461
- Albert Einstein Cancer Center/Montefiore Medical Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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).
- 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.
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Adverse Events and Laboratory Parameters
Time Frame: Throughout study
|
Incidence of adverse signs and/or symptoms (adverse events and laboratory parameters)
|
Throughout study
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pharmacokinetics
Time Frame: MTD confirmation phase of study
|
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.
|
MTD confirmation phase of study
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Sridhar Mani, MD, Albert Einstein College Of Medicine
- Principal Investigator: Pamela N. Munster, MD, Department of Medicine, University of California San Francisco
Publications and helpful links
General 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 record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Protein Kinase Inhibitors
- Gemcitabine
- ON 01910
Other Study ID Numbers
- Onconova 04-10
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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