A Phase 1/2 Study of CS7017, an Oral PPARγ Agonist, in Combination With Paclitaxel

A Phase 1/2 Study of CS7017, an Oral PPARγ Agonist, in Combination With Paclitaxel in Subjects With Advanced Anaplastic Thyroid Cancer

The Phase I/II study will be conducted as an open label, multiple center study of CS-7017, an experimental drug and paclitaxel chemotherapy in subjects with advanced anaplastic thyroid cancer. Biopsies will be obtained from patients with accessible tumor at baseline, two-weeks after the first CS-7017 dosage (prior to the start of combination therapy) and at the end of the first study cycle (week 3 of combination therapy), in order to evaluate the effects of the study drug alone and in combination with the chemotherapy agent on the tumor. Treatment will continue until disease progression or the development of intolerable toxicities.

Study Overview

• Status: Terminated
• Conditions: Anaplastic Thyroid Cancer
• Intervention / Treatment: Drug: CS-7017; Drug: Paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Univ of Colorado Cancer Center
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Massachusetts General Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University, Siteman Cancer Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State Univ
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health Science Univ
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Maloney Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Ingram Cancer Center
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Eastern Virginia Medical School

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

During the Phase 1 and Phase 2 portions of the study, participant eligibility criteria are identical except for prior treatment for anaplastic thyroid cancer (ATC). During Phase 1, eligible participants may have received prior chemotherapy while during Phase 2, eligible participants must be chemotherapy naïve.

Inclusion Criteria:

• Histologically or cytologically diagnosed, advanced ATC
• Measurable lesion(s)
• Lesion(s) (primary or metastatic) with viable tumor tissue accessible for repeated biopsy
• Age equal to or older than 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
• Adequate organ and bone marrow function
• Agreement to use effective contraception while on treatment and for equal to or greater than 3 months after end of treatment
• Pregnant or breastfeeding

Exclusion Criteria:

• Medical history of diabetes mellitus requiring treatment with insulin or oral agents; no pleural or pericardial effusion or clinically significant pulmonary or cardiovascular disease.
• Clinically active brain metastasis, uncontrolled seizure disorder, spinal cord compression, or carcinomatous meningitis
• Clinically significant active infection requiring antibiotic or antiretroviral therapy
• Concomitant use of other thiazolidinediones (TZDs)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cohort 1; 0.15 mg CS-7017; Participants who received 0.15 mg twice daily (BID) oral CS-7017 and 135 [Dose Level 1a] or 175 [Dose Level 1b] mg/m^2 intravenous (IV) paclitaxel once every 3 weeks.	Drug: CS-7017; At Phase 1, CS-7017 will be tested in combination with paclitaxel at the following dosage levels: 0.15, 0.30, or 0.50 mg BID. At Phase 2, CS-7017 will be administered at the recommended phase 2 dose (RP2D).; Drug: Paclitaxel; Commercially available paclitaxel will be administrated as IV infusion over 3 hours once every 3 weeks.
EXPERIMENTAL: Cohort 2; 0.30 mg CS-7017; Participants who received 0.30 mg twice daily (BID) oral CS-7017 and 175 mg/m^2 IV paclitaxel once every 3 weeks.	Drug: CS-7017; At Phase 1, CS-7017 will be tested in combination with paclitaxel at the following dosage levels: 0.15, 0.30, or 0.50 mg BID. At Phase 2, CS-7017 will be administered at the recommended phase 2 dose (RP2D).; Drug: Paclitaxel; Commercially available paclitaxel will be administrated as IV infusion over 3 hours once every 3 weeks.
EXPERIMENTAL: Cohort 3; 0.50 mg CS-7017; Participants who received 0.50 mg twice daily (BID) oral CS-7017 and 175 mg/m^2 IV paclitaxel once every 3 weeks.	Drug: CS-7017; At Phase 1, CS-7017 will be tested in combination with paclitaxel at the following dosage levels: 0.15, 0.30, or 0.50 mg BID. At Phase 2, CS-7017 will be administered at the recommended phase 2 dose (RP2D).; Drug: Paclitaxel; Commercially available paclitaxel will be administrated as IV infusion over 3 hours once every 3 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Progression-free Survival in Participants After a Dosage of CS-7017 Administered Twice Daily in Combination With Paclitaxel Administered Once Every 3 Weeks to Participants With Advanced Anaplastic Thyroid Cancer (ATC)	Progression-free survival (PFS) was defined as the time from enrollment to the date of the first objective documentation of disease progression or death resulting from any cause, whichever comes first. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) as at least a 20% increase in the sum of diameters of target lesions.	From baseline up to disease progression or death, up to approximately 2 years postdose
Overall Survival in Participants After a Dosage of CS-7017 Administered Twice Daily in Combination With Paclitaxel Administered Once Every 3 Weeks to Participants With Advanced Anaplastic Thyroid Cancer (ATC)	Overall survival (OS) was defined as the time from the date enrollment to the date of death.	From baseline up to date of death, up to approximately 2 years postdose
Best Overall Response in Participants After a Dosage of CS-7017 Administered Twice Daily in Combination With Paclitaxel Administered Once Every 3 Weeks to Participants With Advanced Anaplastic Thyroid Cancer (ATC)	The best overall response was the best response (in the order of confirmed complete response [CR], confirmed partial response [PR], stable disease [SD], and progressive disease [PD]) among all overall responses recorded from the start of treatment until the subject withdraws from the study. If there is no tumor assessment after the date of enrollment, the best overall response is classified as Unknown.	From baseline up to disease progression or the development of unacceptable toxicity, up to approximately 2 years postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC)	Treatment-emergent adverse events (TEAEs) are defined as adverse events that started or worsened after the first dose of any study drug (after Day 1 or first day of CS-7017 monotherapy) but adverse events occurring more than 30 days after the last dose are not considered TEAEs unless also considered to be related (possibly, probably, or definitely) to study drug.	From baseline up to 30 days after last dose, up to approximately 2 years

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (ACTUAL): December 1, 2011
• Study Completion (ACTUAL): December 1, 2011

Study Registration Dates

• First Submitted: January 15, 2008
• First Submitted That Met QC Criteria: January 28, 2008
• First Posted (ESTIMATE): January 29, 2008

Study Record Updates

• Last Update Posted (ACTUAL): September 16, 2020
• Last Update Submitted That Met QC Criteria: August 31, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Anaplastic Thyroid Cancer; Neoplasm; Tumor; Anti-neoplastic Agent; First-line treatment of advanced Anaplastic thyroid cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Thyroid Diseases; Thyroid Neoplasms; Thyroid Carcinoma, Anaplastic; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Efatutazone
• Other Study ID Numbers: CS7017-A-U103

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