Study of an Experimental New Drug, PPARγ Agonist Taken by Mouth by Participants With Advanced or Metastatic Cancer

Study Overview
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Brief Summary
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An open-label, Phase I, dose escalation study of CS-7017 administered by mouth in sequential cohorts of 3 to 6 participants with advanced or metastatic malignancies.

Official Title
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A Phase I Dose Finding Study of an Experimental New Drug, PPARγ Agonist Taken by Mouth by Patients With Advanced or Malignancies

Conditions
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Neoplasm

Intervention / Treatment
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* Drug: CS-7017


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically diagnosed advanced or metastatic malignancy that is refractory to, not curable with, or not eligible for standard treatment(s). 18 years or older Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2. Resolution of any toxic effects of prior therapy (except alopecia) to National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 grade less than or equal to 1. Adequate organ and bone marrow function. Willing to use effective contraceptive while on treatment through at least 3 months thereafter. Negative pregnancy test for females of childbearing potential. Echocardiogram with ejection fraction within normal range. Exclusion Criteria: Anticipation of need for a major surgical procedure or radiation therapy during the study. Treatment with chemotherapy, hormonal therapy, other thiazolidinediones, radiotherapy, minor surgery, or any investigational agent within 4 weeks (6 weeks for nitrosoureas, mitomycin C, immunotherapy, biological therapy, or major surgery) of study treatment start. Participants with clinically significant pleural or pericardial effusion (participants with minimal pleural effusion may be eligible at the Investigator's discretion). Clinically significant active infection, which requires antibiotic therapy, or human immunodeficiency virus (HIV)-positive participants receiving antiretroviral therapy.

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: CS-7017<br>CS-7017 from 0.05 to 3.2 mg bid | Drug: CS-7017<br>* CS-7017 0.05mg and 1.0mg tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions). Objective response rate was defined as the sum of all CRs and PRs. | Baseline up to at least 2 cycles (each cycle was 3 weeks), up to 2 years 5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summary of Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Area under the plasma/serum drug concentration-time curve for dosing interval (AUC[0-tau]), computed using the linear trapezoidal rule and area under the plasma/serum drug concentration-time curve from 0 to last time point above the quantification limit (AUC[0-t]) calculated using the linear trapezoidal rule were assessed. | Day 1 of Cycles 1 and 2: predose, 0.5, 1, 2, 3, 4, 6, and 10 hours postdose; and predose on Day 8 and 15 of Cycle 1. | 
| Summary of Pharmacokinetic Parameter Observed Maximum Plasma Concentration (Cmax) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies | Cmax was defined as observed maximum plasma concentration. | Day 1 of Cycles 1 and 2: predose, 0.5, 1, 2, 3, 4, 6, and 10 hours postdose; and predose on Day 8 and 15 of Cycle 1. | 
| Summary of Pharmacokinetic Parameter Terminal Elimination Half-life (t1/2) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies |  | Day 1 of Cycles 1 and 2: predose, 0.5, 1, 2, 3, 4, 6, and 10 hours postdose; and predose on Day 8 and 15 of Cycle 1. | 
| Summary of Pharmacokinetic Parameter Time of Maximum Plasma Concentration (Tmax) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies | Tmax was defined as time of maximum plasma concentration. | Day 1 of Cycles 1 and 2: predose, 0.5, 1, 2, 3, 4, 6, and 10 hours postdose; and predose on Day 8 and 15 of Cycle 1. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PPARγ agonist, advanced or metastatic malignancies, Tumor, Cancer