Safety of 24-hour Infusion of ON 01910.Na in Combination With Gemcitabine in Advanced Solid Tumors

NCT01165905 | Completed Phase 1

• 1 other identifier: Onconova 04-10
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief 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 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.

Conditions

Solid Tumor

Keywords

cancer; solid malignancy; tumor; malignant neoplasm; histologically confirmed solid malignancy

Outcome Measures

Primary Outcomes (1)

• Adverse Events and Laboratory Parameters

  Incidence of adverse signs and/or symptoms (adverse events and laboratory parameters)

  Throughout study

Secondary Outcomes (1)

• Pharmacokinetics

  MTD confirmation phase of study

Interventions

ON 01910.Na DRUG

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.

Also known as: rigosertib sodium

Gemcitabine DRUG

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.

Also known as: Gemzar, gemcitabine HCl, 2´-deoxy-2´,2´-difluorocytidine monohydrochloride (-isomer), gemcitabine for injection, USP, nucleoside metabolic inhibitor

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Traws Pharma, Inc.: lead

Study Sites (2)

Department of Medicine, University of California San Francisco

San Francisco, California, 94143, United States

Location

Albert Einstein Cancer Center/Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

Related Publications (1)

• 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.

  RESULT

MeSH Terms

Conditions

Neoplasms

Interventions

ON 01910; Gemcitabine; Isomerism; Injections

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Molecular Structure; Biochemical Phenomena; Chemical Phenomena; Organic Chemistry Phenomena; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Sridhar Mani, MD

  Albert Einstein College of Medicine

  PRINCIPAL INVESTIGATOR

• Pamela N. Munster, MD

  Department of Medicine, University of California San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2010
• First Posted: July 20, 2010
• Study Start: January 1, 2010
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: June 23, 2017

Record last verified: 2017-06

Locations

US (2)