Safety of ON 01910.Na as a 3-day Infusion in Patients With Advanced Cancer

NCT01538537 | Completed Phase 1

• 1 other identifier: Onconova 04-02
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to determine the largest dose of ON 01910.Na (rigosertib sodium) that can be given safely as a 3-day continuous infusion once every 2 weeks (2-week cycle) in patients with advanced cancer.

Conditions

Advanced Cancer; Solid Tumors; Cancer; Neoplasms

Keywords

ON 01910.Na; rigosertib Sodium; rigosertib

Outcome Measures

Primary Outcomes (1)

• Number of dose limiting toxicities (DLTs)

  DLTs are defined as: * Grade 3 non-hematological toxicity other than nausea, vomiting, diarrhea, fever, stomatitis, esophagitis/dysphagia. * Grade 3 nausea and vomiting uncontrolled by antiemetics; Grade 3 diarrhea uncontrolled by antidiarrheal agents; Grade 3 drug-induced fever uncontrolled by antipyretics. * Grade 3 stomatitis and/or esophagitis/dysphagia lasting \>3 days. * Grade 4 neutropenia or thrombocytopenia lasting \>5 days. * Episode of neutropenic fever, as defined in Protocol. * Failure to recover neutrophils (\>1,500 per microliter) or platelets (\>75,000 per microliter) by day 28.

  28 days after start of first administration of ON 01910.Na

Secondary Outcomes (5)

• Number of Adverse Events (AEs)

  30 days after last infusion of study drug

• Severity of Adverse Events

  30 days after last infusion of study drug

• Relationship of Adverse Events (AEs) to Study Treatment

  30 days after last infusion of study drug

• Concentration of ON 01910.Na in plasma versus time

  Up to 72 hours after end of infusion of study drug in Cycles 1 and 4

• Change in size of target lesions recorded at baseline

  30 days after last infusion of study drug

Interventions

rigosertib sodium DRUG

ON 01910.Na will be supplied as a sterile, concentrated solution (75 mg/ml) in labeled, sealed glass vials. ON 01910.Na concentrated solution (75 mg/ml) must be diluted before intravenous administration. The starting dose will be 50 mg/m2 over 24 hour infusion daily for 3 days. A fresh infusion must be prepared for each day of the 3-day continuous infusion. This 3-day continuous treatment followed by 11 days without administration of study drug will constitute 1 Cycle. Cycles can be repeated every 2 weeks. The dosing of ON 01910.Na will be based on body surface area (BSA). In the absence of toxicity that would cause accelerated dose escalation to cease, drug doses are planned to escalate every 3 weeks.

Also known as: ON 01910.Na Concentrate, ON 01910.Na, rigosertib

Eligibility Criteria

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

You may qualify if:

• Patient must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.
• At least 4 weeks since the last dose of other potentially myelosuppressive treatment (at least 6 weeks since last dose of nitrosoureas or mitomycin C) and recovery from manifestations of reversible drug toxicity (except alopecia, stable residual neuropathy, and residual hand and foot syndrome). Among patients with prior doxorubicin chemotherapy, only those with no more than 450 mg/m2 of the drug will be entered. It must be at least 4 weeks since prior chemotherapy or radiation therapy, 6 weeks if the last regimen included nitrosoureas or mitomycin C.
• Patients with prior radiotherapy are eligible provided that a minimum of 4 weeks have passed and that the maximal area of hematopoietic active bone marrow treated was less than 25%.
• ECOG performance status \< 2.
• Hgb \> 10 gm/dl
• WBC \> 4,000 per microliter
• Absolute neutrophil count \> 1,500 per microliter
• Platelets \>100,000 per microliter
• Total bilirubin within normal institutional limits
• AST(SGOT)/ALT(SGPT) values within limits defined by Protocol
• Creatinine within normal institutional limits or creatinine clearance \>60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
• Women of child-bearing potential and men must agree to use adequate contraception.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Patients who have had recent major surgery (within the past 14 days), chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (except alopecia, stable residual neuropathy, and residual hand and foot syndrome) due to previously administered agents.
• Patients may not be receiving any other investigational agents or concurrent chemotherapy, radiotherapy, hormonal treatments, or immunotherapy while on study.
• Patients with known or clinical evidence of central nervous system metastasis, 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.
• The patient should have no major 3rd space fluid, ascites requiring active medical management including paracentesis, peripheral bilateral edema, or hyponatremia (serum sodium value less than 134 Meq/L).
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, bleeding, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant and nursing women are excluded from this study.
• HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study.

Sponsors & Collaborators

• Traws Pharma, Inc.: lead

Study Sites (1)

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Related Publications (2)

• Ohnuma T, Lehrer D, Ren C, Cho SY, Maniar M, Silverman L, Sung M, Gretz HF 3rd, Benisovich V, Navada S, Akahoho E, Wilck E, Taft DR, Roboz J, Wilhelm F, Holland JF. Phase 1 study of intravenous rigosertib (ON 01910.Na), a novel benzyl styryl sulfone structure producing G2/M arrest and apoptosis, in adult patients with advanced cancer. Am J Cancer Res. 2013 Jun 20;3(3):323-38. Print 2013.

  PMID: 23841031 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

Conditions

Neoplasms

Interventions

ON 01910

Study Officials

• Takao Ohnuma, MD

  Icahn School of Medicine at Mount Sinai

  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: February 20, 2012
• First Posted: February 24, 2012
• Study Start: August 1, 2006
• Primary Completion: October 1, 2010
• Study Completion: January 1, 2012
• Last Updated: June 23, 2017

Record last verified: 2017-06

Locations

US (1)