Safety, Pharmacokinetics and Clinical Activity of Oral Rigosertib in Solid Tumors

NCT01168011 | Completed Phase 1 DMC

• 2 other identifiers: Onconova 09-04COMIRB # 10-0150
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1 study in which 2 to 72 patients with advanced cancer will receive oral doses of rigosertib, a new investigational (unapproved) anti-cancer drug. The objective of the study is to determine the highest dose of drug that can be given safely. The study will start by testing a low dose. If this dose is safe, then, higher and higher doses will be tested as long as the previous lower dose was safe. Safety will be determined by looking for any side effects or unusual laboratory values. It is important to know the highest safe dose so that additional studies can be done. The drug will be given in the form of capsules twice or three times a day for 21 consecutive days of 21-day cycles.

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (1)

• Adverse Events

  Adverse events (AEs) will be regarded as treatment emergent signs and symptoms (TESS) if they started on or after the date and time of administration of the first dose of study drug, or if they were present prior to the administration of the first dose of study drug and increased in severity during the study. Adverse events include clinical laboratory parameters (e.g., Hematology Panel and Serum Chemistry Panel). Other safety parameters include vital signs, physical examination findings, concomitant medications, and drug exposure.

  2 years

Secondary Outcomes (3)

• Concentration of ON 01910.Na in plasma

  2 years

• Measurement of tumor size

  2 years

• Concentration of ON 01910.Na in Urine

  1 years

Study Arms (1)

rigosertib

EXPERIMENTAL

Doses of rigosertib up to 700 mg twice a day or three times a day every day of 21-day cycles.

Drug: rigosertib

Interventions

rigosertib DRUG

Doses of rigosertib up to 700 mg twice a day or three times a day for 21 days of 21-day cycles. Treatment may continue until progression.

Also known as: rigosertib sodium, 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:

• 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.
• ECOG performance status 2, 1 or 0.
• Life expectancy greater than 6 months.
• One or more measurable lesion(s) ("target lesion\[s\]"), that can be accurately measured in at least 1 dimension with longest diameter equal to or greater than 20 mm using conventional techniques (computed tomography \[CT\] scan or magnetic resonance imaging \[MRI\]) or equal to or greater than 10 mm with spiral CT scan.
• If female, has a negative screening for pregnancy. Women of child-bearing potential and men must agree to use adequate contraception prior to study entry (hormonal or barrier method of birth control; abstinence) and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Ability to understand the nature of the study and any hazards of participating in it, to communicate satisfactorily with the investigator, and to participate in, and comply with, the requirements of the entire study.
• Willing to adhere to the prohibitions and restrictions specified in this protocol.
• Patient must have signed an informed consent document.

You may not qualify if:

• Recent major surgery (within the past 14 days).
• Chemotherapy or dose of other potentially myelosuppressive treatment within 3 weeks prior to entering the study (6 weeks for nitrosoureas or mitomycin C).
• Among patients with prior doxorubicin chemotherapy, only those with no more than a total cumulative dose of 450 mg/m2 of the drug.
• Definitive radiotherapy (over 10 fractions and maximal area of hematopoietic active bone marrow treated was greater than 25%) within 4 weeks prior to entering the study.
• Palliative radiotherapy (10 or less fractions) within 2 weeks prior to entering the study.
• Residual adverse events (except alopecia, stable residual neuropathy, and residual hand, foot syndrome) and ascites requiring active medical management including paracentesis, peripheral bilateral edema, hyponatremia (serum value less than 130 Meq/L) due to previously administered agents, which have not recovered at grade 1 severity level or below before study entry.
• Receiving any other investigational agents or concurrent chemotherapy, radiotherapy, hormonal treatments, bone marrow transplantation, or immunotherapy while on study. Exceptions are long-term hormonals for prostate (e.g. goserelin) and octreotide for neuroendocrine malignancies.
• Previous bone marrow transplant.
• 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.
• Hgb less than 9 gm/dL (must not require transfusional support but erythropoietin therapy is permitted).
• WBC less than 4,000/microliter.
• Absolute neutrophil count less than 1,500/microliter.
• Platelets less than or equal to 100,000/microliter.

Sponsors & Collaborators

• Traws Pharma, Inc.: lead

Study Sites (1)

University of Colorado at Denver Health and Sciences

Denver, Colorado, 80045, 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

Related Links

• Clinical Trials at University of Colorado Hospital

MeSH Terms

Interventions

ON 01910

Study Officials

• Antonio Jimeno, MD, PhD

  University of Colorado at Denver Health and Sciences

  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 22, 2010
• Study Start: July 1, 2010
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: June 23, 2017

Record last verified: 2017-06

Locations

US (1)