Dose Escalation Study of Gemcitabine and ON 01910.Na in Solid Tumors

NCT01125891 | Completed Phase 1

• 1 other identifier: 04-09
• Study Type: interventional
• Target: 39
• 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. This study is designed to answer that question.

Conditions

Malignant Neoplasmas; Solid Tumors

Keywords

gemcitabine hydrochloride; Gemzar; ON 01910.Na

Outcome Measures

Primary Outcomes (2)

• Adverse events

  Incidence of adverse events, including laboratory parameters, as assessed by NCI CTCAE v3.0.

  Start of treatment to 30 days after end of treatment.

• Maximum tolerated dose (MTD) of ON 01910.Na

  MTD will be defined as the highest dose level of ON 01910.Na at which none of the first three patients or no more than one of six patients experienced dose limiting toxicity (DLT) in course 1.

  Escalation phase of protocol.

Secondary Outcomes (3)

• Pharmacokinetics

  Confirmation phase of protocol.

• Tumor measurements

  Screening to 30 days after end of treatment.

• Pharmacodynamics, ex vivo

  Confirmation phase of protocol.

Study Arms (1)

gemcitabine and ON 01910.Na

EXPERIMENTAL

Drug: gemcitabine; Drug: ON 01910.Na

Interventions

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 and ON 01910.Na

ON 01910.Na DRUG

The starting dose of ON 01910.Na is 600 mg/m2 as a 2 hour intravenous (i.v.) infusion on days 1, 4, 8, 11, 15 and 18 of a 28-day course. The dose of ON 01910.Na will be escalated in increments in successive cohorts (dose level (DL) 1 = 600 mg/m2, DL 2 = 1200 mg/m2, DL 3 = 1800 mg/m2) of new patients.

Also known as: rigosertib sodium

gemcitabine and ON 01910.Na

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.
• Patients must have a life expectancy of at least 12 weeks and an ECOG performance status of \<1.
• 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 a total bilirubin value of up to 1.5 mg/dl and 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.
• They have an active infectious process.
• They have active central nervous system metastases.
• They have received prior radiotherapy administered to more than 30% of marrow-bearing bone mass.
• They have ascites requiring active medical management including paracentesis more than twice a month or hyponatremia (defined as serum sodium value of \<134 Meq/L).
• Women who are pregnant or lactating.
• Male patients with female sexual partners who are unwilling to follow the strict contraception requirements described in this protocol (see Section 5.4).
• Patients who 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)

University of Colorado Cancer Center

Denver, Colorado, 80045, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Related Publications (5)

• Jimeno A, Li J, Messersmith WA, Laheru D, Rudek MA, Maniar M, Hidalgo M, Baker SD, Donehower RC. Phase I study of ON 01910.Na, a novel modulator of the Polo-like kinase 1 pathway, in adult patients with solid tumors. J Clin Oncol. 2008 Dec 1;26(34):5504-10. doi: 10.1200/JCO.2008.17.9788. Epub 2008 Oct 27.

  PMID: 18955447 BACKGROUND

• Jimeno A, Chan A, Cusatis G, Zhang X, Wheelhouse J, Solomon A, Chan F, Zhao M, Cosenza SC, Ramana Reddy MV, Rudek MA, Kulesza P, Donehower RC, Reddy EP, Hidalgo M. Evaluation of the novel mitotic modulator ON 01910.Na in pancreatic cancer and preclinical development of an ex vivo predictive assay. Oncogene. 2009 Jan 29;28(4):610-8. doi: 10.1038/onc.2008.424. Epub 2008 Nov 24.

  PMID: 19029951 BACKGROUND

• Jimeno A, Rubio-Viqueira B, Rajeshkumar NV, Chan A, Solomon A, Hidalgo M. A fine-needle aspirate-based vulnerability assay identifies polo-like kinase 1 as a mediator of gemcitabine resistance in pancreatic cancer. Mol Cancer Ther. 2010 Feb;9(2):311-8. doi: 10.1158/1535-7163.MCT-09-0693. Epub 2010 Jan 26.

  PMID: 20103597 BACKGROUND

• Ma WW, Messersmith WA, Dy GK, Weekes CD, Whitworth A, Ren C, Maniar M, Wilhelm F, Eckhardt SG, Adjei AA, Jimeno A. Phase I study of Rigosertib, an inhibitor of the phosphatidylinositol 3-kinase and Polo-like kinase 1 pathways, combined with gemcitabine in patients with solid tumors and pancreatic cancer. Clin Cancer Res. 2012 Apr 1;18(7):2048-55. doi: 10.1158/1078-0432.CCR-11-2813. Epub 2012 Feb 14.

  PMID: 22338014 RESULT

• 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

Interventions

Gemcitabine; ON 01910

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Antonio Jimeno, MD, PhD

  University of Colorado at Denver Health and Sciences Center

  STUDY CHAIR

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: May 17, 2010
• First Posted: May 19, 2010
• Study Start: January 1, 2009
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: June 23, 2017

Record last verified: 2017-06

Locations

US (2)