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

Phase 2TerminatedNCT00603941

Daiichi Sankyo19 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Anaplastic Thyroid Cancer

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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)

Locations (10)

Univ of Colorado Cancer Center

Aurora, Colorado, United States

Mayo Clinic

Jacksonville, Florida, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

Washington University, Siteman Cancer Center

St Louis, Missouri, United States

Ohio State Univ

Columbus, Ohio, United States

Oregon Health Science Univ

Portland, Oregon, United States

University of Pennsylvania Maloney Hospital

Philadelphia, Pennsylvania, United States

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, United States

Eastern Virginia Medical School

Norfolk, Virginia, United States

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: From baseline up to disease progression or the development of unacceptable toxicity, up to approximately 2 years postdose

Secondary Outcomes

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.

Time frame: From baseline up to 30 days after last dose, up to approximately 2 years