Safety of 24-Hour Infusion of ON 01910.Na in Patients With Advanced Cancer

NCT01538563 | Completed Phase 1

• 1 other identifier: Onconova 04-03
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of this study is to determine the highest dose of ON 01910.Na that can be safely given as an intravenous infusion over 24 hours once a week in a 3-week cycle to patients with advanced solid tumors.

Conditions

Solid Tumors; Advanced Cancer; Cancer; Neoplasms

Keywords

ON 01910.Na; rigosertib sodium; rogosertib

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. * Recurrent grade 3 toxicity uncontrolled by optimal therapy or Grade 4 nausea, vomiting, diarrhea and fever. * Grade 3 stomatitis and/or esophagitis/dysphagia for \> 5 days. * Grade 4 neutropenia or thrombocytopenia for \> 5 days measured at least 2X 2-3 days apart. * Neutropenic fever, as defined in Protocol. * Failure to recover neutrophils (\> 1,500 per microliter) or platelets (\>75,000 per microliter) before the next weekly dose.

  21 days after 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 (AEs)

  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 48 hours after infusion of study drug during Week 1 in Cycles 1 and 2

• Change in size of target lesions recorded at baseline

  30 days after last infusion of study drug

Interventions

rigosertib sodium DRUG

Patients will receive escalating doses of ON 01910.Na (250 mg/m2 to 4450 mg/m2) intravenously by 24 hour continuous infusion once every week (3 weeks per cycle), until evidence of disease progression, intolerable adverse events, or withdrawal of patient consent.

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:

• Must have 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.
• Patients with disease amenable to sequential biopsies will be requested to undergo two tumor biopsies and two normal skin biopsies, but patients may decline and still be eligible for enrollment during this escalation stage.
• At least 3 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 (alopecia, stable residual neuropathy, and residual hand and foot syndrome are excluded). Patients with prior doxorubicin chemotherapy must have total cumulative dose of no more than 450 mg/m2.
• Patients with prior radiotherapy are eligible provided a minimum of 4 weeks have passed and the maximal area of hematopoietic active bone marrow treated was less than 25%.
• ECOG performance status ≤2.
• Patients must have nearly normal organ and marrow function as defined below:
• Hgb \> 9 gm/dl (must not require transfusional support but erythropoietin therapy is permitted)
• WBC \> 4,000 per microliter
• Absolute neutrophil count \> 1,500 per microliter
• Platelets ≥ 100,000 per microliter
• Total bilirubin within 1.5 times institutional upper normal limit
• AST(SGOT)/ALT(SGPT) ≤ 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. Patients with primary liver disease with these parameters will be ineligible.)
• Serum creatinine within normal institutional limits or estimated 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 prior to study entry.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Recent major surgery (within the past 14 days), chemotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) or radiotherapy within 4 weeks 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 on any other investigational agents or concurrent chemotherapy, radiotherapy, hormonal treatments, bone marrow transplantation, or immunotherapy. Patients who have previously had a Bone Marrow Transplant are excluded from this study.
• 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 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.
• HIV-positive patients receiving combination anti-retroviral therapy are excluded.
• Ascites requiring active medical management including paracentesis, peripheral bilateral edema, hyponatremia (serum sodium value less than 134 Meq/L).

Sponsors & Collaborators

• Traws Pharma, Inc.: lead

Study Sites (1)

Albert Einstein Cancer 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

Study Officials

• Sridhar Mani, MD

  Albert Einstein College of Medicine

  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: June 1, 2006
• Primary Completion: July 1, 2010
• Study Completion: November 1, 2011
• Last Updated: June 23, 2017

Record last verified: 2017-06

Locations

US (1)