A Phase 1 Dose-Escalation Study of the Safety and Clinical Effects of ON 01910.Na in Combination With Either Irinotecan or Oxaliplatin in Patients With Advanced Solid Tumors
- Male and female patients ≥18 years of age with histologically or cytologically
confirmed solid tumors that are metastatic or progressive, for whom no standard
therapy holds curative potential and for whom irinotecan or oxaliplatin are
reasonable treatment options.
- Patients must have evaluable disease, either measurable on imaging or with
informative tumor marker(s).
- Eastern Collaborative Oncology Group (ECOG) Performance Status of ≤2.
- Life expectancy >12 weeks.
- Any acute or chronic adverse effects of prior chemotherapy have resolved to
as determined by CTCAE v3 criteria.
- Existing or planned central venous access with a 2-channel infusion catheter system.
- Laboratory values meet the following criteria: Absolute neutrophil count ≥1,500
cells/µL; Platelets ≥100,000 cells/µL; Total bilirubin ≤1.5 times the upper limit of
normal; AST (SGOT) ≤2.5 times the upper limit of normal; ALT (SGPT) ≤2.5 times the
upper limit of normal; Serum creatinine ≤1.5 mg/dL or a measured creatinine clearance
≥50 mL/min; Negative βhCG test in women of childbearing potential (defined as women
≤50 years of age or history of amenorrhea for ≤12 months prior to study entry).
- Patients with primary liver cancer or hepatic metastasis are eligible to enroll,
provided they meet the following: Total bilirubin is ≤2 mg/dL; AST and ALT are each
≤5 times the institutional upper limit of normal; Ascites, if present, is manageable
with diuretic agents alone.
- If there is a history of treated brain metastases, these must have been clinically
stable for ≥4 weeks prior to enrollment.
- UGT1A1 genotype of patient must be known or a UGT1A1 genotype test must be done for
patients being considered for treatment in Group A.
- Women who are pregnant or lactating.
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study.
- Severe liver dysfunction (Child-Pugh Class C or uncompensated Class B with persistent
encephalopathy, persistent ascites, or prothrombin time >1.5 times the upper limit of
normal) is present.
- Patients with a history of esophageal bleeding are excluded unless varices have been
sclerosed or banded and bleeding episodes have not occurred during the prior 6
- Contraindications, including known hypersensitivity, to the assigned chemotherapy
agent (i.e., irinotecan or oxaliplatin).
- Prior receipt of ON 01910.Na or prior participation in this protocol.
- Use of any investigational agents within 4 weeks of study enrollment.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection or psychiatric illness/social situations that would limit compliance with
study requirements, as determined by the Investigator.
- Patients who are homozygous for the UGT1A1*28 allele will be excluded from
participating in Group A of this protocol.
- Patients with ascites requiring active medical management including paracentesis,
peripheral bilateral edema or hyponatremia (defined as serum sodium value of <134