RTA 402 in Patients With Advanced Solid Tumors or Lymphoid Malignancies

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

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

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors; Lymphoid Malignancies
• Intervention / Treatment: Drug: Bardoxolone methyl

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.

Study Sponsor, originally Reata Pharmaceuticals, Inc., is now Reata Pharmaceuticals, Inc., a wholly owned subsidiary of Biogen.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bardoxolone methyl capsules; 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; Other Names: RTA 402

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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)

Collaborators and Investigators

• Sponsor: Reata, a wholly owned subsidiary of Biogen

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2006
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: September 12, 2007
• First Submitted That Met QC Criteria: September 12, 2007
• First Posted (Estimated): September 14, 2007

Study Record Updates

• Last Update Posted (Actual): February 2, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: 402-C-0501

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/