Advanced Solid Tumors, Lymphoid Malignancies
Conditions
Brief summary
This study assesses the tolerability, safety, efficacy and pharmacokinetics of Bardoxolone methyl (RTA 402) in advanced solid tumors and lymphoid malignancies.
Detailed description
Bardoxolone methyl (RTA 402) is a synthetic triterpenoid that has demonstrated significant in vivo single agent anti-cancer activity. This is an open-label phase I dose-escalation study of Bardoxolone methyl (RTA 402) administered orally for the first 21 days of a 28-day cycle.
Interventions
Sponsors
Biogen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histopathological documentation of solid tumor or lymphoid malignancy. * Advanced or metastatic cancer that is either refractory to or have relapsed after standard-of-care curative or survival-prolonging therapy, or for whom no such therapies exist. * ECOG performance status of less than or equal to 2 * Adequate liver and renal function as documented by the following laboratory test results within 14 days of starting therapy: total bilirubin ≤ 1.5 mg/dL; AST (SGOT) and ALT(SGPT) ≤ 2.5 ULN or ≤ 5 ULN if liver is involved by tumor; serum creatinine ≤2.0 mg/dL OR creatinine clearance \>60 mL/min. * Adequate bone marrow function as documented by the following laboratory test results within 14 days of starting therapy: platelets greater than 100,000/mm3, absolute granulocyte count greater than 1,500/mm3, hemoglobin greater than or equal to 8.0 g/dl. * Completion of prior chemotherapy, hormonal therapy, radiation therapy, biological therapy, or other investigational cancer therapy, for at least 4 weeks prior to study entry and must have recovered from all acute side effects (to CTC grade 1 or less) prior to initiation of RTA 402. Patients who were receiving mitomycin C or nitrosoureas must be 6 weeks from the last administration of chemotherapy. * Agree to practice effective contraception during the entire study period. * Life expectancy of more than 3 months * Able and willing to sign the informed consent form. * Willing and able to self-administer orally and document all doses of RTA 402 ingested.
Exclusion criteria
* Active brain metastases or primary CNS malignancies. * Pregnant or breast feeding * Clinically significant illnesses including, but not limited to: Uncontrolled diabetes; Active or uncontrolled infection; Acute or chronic liver disease; Confirmed diagnosis of HIV infection; Uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, or uncontrolled cardiac arrhythmia. * Psychiatric illness that would limit compliance with study requirements.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine the dose-limiting toxicity, maximum tolerated dose, and recommended phase II dose of Bardoxolone methyl Capsules | 28 day cycles, with a maximum of 18 cycles (18 months) |
| To characterize the pharmacokinetics of Bardoxolone methyl in this patient population. | 28 day cycles, with a maximum of 18 cycles (18 months) |
Secondary
| Measure | Time frame |
|---|---|
| To document any preliminary antitumor activity. | 28 day cycles, with a maximum of 18 cycles (18 months) |
| To determine the in vivo molecular and biological effects. | 28 day cycles, with a maximum of 18 cycles (18 months) |
| To correlate the biological activity of RTA 402 with drug concentration in plasma and blood cellular elements. | 28 day cycles, with a maximum of 18 cycles (18 months) |
Countries
United States
Outcome results
None listed