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

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

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.

Study Overview

• Status: Completed
• Conditions: Neoplasm
• Intervention / Treatment: Drug: CS-7017

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States
  • Massachusetts
    • Boston, Massachusetts, United States

Participation Criteria

Eligibility Criteria

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

Description

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.

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: CS-7017; CS-7017 from 0.05 to 3.2 mg bid	Drug: CS-7017; CS-7017 0.05mg and 1.0mg tablets

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Daiichi Sankyo, Inc.
• Investigators: Study Director: Study Clinical Lead, Daiichi Sankyo, Inc.

Publications and helpful links

General Publications

• Pishvaian MJ, Marshall JL, Wagner AJ, Hwang JJ, Malik S, Cotarla I, Deeken JF, He AR, Daniel H, Halim AB, Zahir H, Copigneaux C, Liu K, Beckman RA, Demetri GD. A phase 1 study of efatutazone, an oral peroxisome proliferator-activated receptor gamma agonist, administered to patients with advanced malignancies. Cancer. 2012 Nov 1;118(21):5403-13. doi: 10.1002/cncr.27526. Epub 2012 May 8.

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): February 1, 2010
• Study Completion (Actual): February 1, 2010

Study Registration Dates

• First Submitted: December 6, 2006
• First Submitted That Met QC Criteria: December 6, 2006
• First Posted (Estimate): December 7, 2006

Study Record Updates

• Last Update Posted (Actual): October 19, 2020
• Last Update Submitted That Met QC Criteria: September 23, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Cancer; Tumor; PPARγ agonist; advanced or metastatic malignancies
• Additional Relevant MeSH Terms: Antineoplastic Agents; Efatutazone
• Other Study ID Numbers: CS7017-A-U102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR