RTA 402 in Patients With Advanced Solid Tumors or Lymphoid Malignancies

Biogen

Status and phase: Completed; Phase 1

Conditions: Lymphoid Malignancies; Advanced Solid Tumors

Treatments: Drug: Bardoxolone methyl

Study type: Interventional

Funder types: Industry

Identifiers

NCT00529438

402-C-0501

Details and patient eligibility

About

This study assesses the tolerability, safety, efficacy and pharmacokinetics of Bardoxolone methyl (RTA 402) in advanced solid tumors and lymphoid malignancies.

Full 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.

Enrollment: 47 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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47 participants in 1 patient group

Bardoxolone methyl capsules

Experimental group

Description:

Bardoxolone methyl to be taken orally for 21 consecutive days, once a day, in the morning prior to food intake. Patients to continue to receive treatment for the first 21 days of each 28-day cycle until they experience intolerable toxicity, show evidence of disease progression, or receive a maximum of 18 cycles (18 months).

Treatment:

Drug: Bardoxolone methyl