RTA 402 in Patients With Advanced Solid Tumors or Lymphoid Malignancies

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

Detailed Description
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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. This study was previously posted by Reata Pharmaceuticals. In September 2023, sponsorship of the trial was transferred to Biogen.

Official Title
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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

Conditions
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Advanced Solid Tumors, Lymphoid Malignancies

Intervention / Treatment
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* Drug: Bardoxolone methyl


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bardoxolone methyl capsules<br>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). | Drug: Bardoxolone methyl<br> <br> * Other names: RTA 402;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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) |