Clinical trial NCT00529438: RTA 402 in Patients With Advanced Solid Tumors or Lymphoid Malignancies
Official title: A Phase I Dose-finding and Pharmacokinetic Study of RTA 402 (CDDOMe) Administered Orally for 21 Days of a 28-day Cycle in Patients With Advanced Solid Tumors or Lymphoid Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lymphoid Malignancies
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2007-09-14
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: To determine the dose-limiting toxicity, maximum tolerated dose, and recommended phase II dose of Bardoxolone methyl Capsules
timeFrame: 28 day cycles, with a maximum of 18 cycles (18 months)
measure: To characterize the pharmacokinetics of Bardoxolone methyl in this patient population.
timeFrame: 28 day cycles, with a maximum of 18 cycles (18 months)
Secondary outcomes:
measure: To document any preliminary antitumor activity.
timeFrame: 28 day cycles, with a maximum of 18 cycles (18 months)
measure: To determine the in vivo molecular and biological effects.
timeFrame: 28 day cycles, with a maximum of 18 cycles (18 months)
measure: To correlate the biological activity of RTA 402 with drug concentration in plasma and blood cellular elements.
timeFrame: 28 day cycles, with a maximum of 18 cycles (18 months)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
References: