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

NCT00603941 | Terminated Phase 1 Results

• 1 other identifier: CS7017-A-U103
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 10

Brief Summary

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.

Conditions

Anaplastic Thyroid Cancer

Keywords

Anaplastic Thyroid Cancer; Neoplasm; Tumor; Anti-neoplastic Agent; First-line treatment of advanced Anaplastic thyroid cancer

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (1)

• 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)

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

Study Arms (3)

Cohort 1; 0.15 mg CS-7017

EXPERIMENTAL

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; Drug: Paclitaxel

Cohort 2; 0.30 mg CS-7017

EXPERIMENTAL

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; Drug: Paclitaxel

Cohort 3; 0.50 mg CS-7017

EXPERIMENTAL

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; Drug: Paclitaxel

Interventions

CS-7017 DRUG

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).

Cohort 1; 0.15 mg CS-7017; Cohort 2; 0.30 mg CS-7017; Cohort 3; 0.50 mg CS-7017

Paclitaxel DRUG

Commercially available paclitaxel will be administrated as IV infusion over 3 hours once every 3 weeks.

Cohort 1; 0.15 mg CS-7017; Cohort 2; 0.30 mg CS-7017; Cohort 3; 0.50 mg CS-7017

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (10)

Univ of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University, Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

Ohio State Univ

Columbus, Ohio, 43210, United States

Location

Oregon Health Science Univ

Portland, Oregon, 97239, United States

Location

University of Pennsylvania Maloney Hospital

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Eastern Virginia Medical School

Norfolk, Virginia, 23507, United States

Location

MeSH Terms

Conditions

Thyroid Carcinoma, Anaplastic; Neoplasms

Interventions

efatutazone; Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Limitations and Caveats

The study was halted prematurely due to low enrollment and failure to establish recommendation of Phase 2 dose. Analysis for the primary efficacy outcomes were also combined for the study.

Results Point of Contact

• Title: Contact for Clinical Trial Information
• Organization: Daiichi Sankyo

CTRinfo@dsi.com

908-992-6400

Study Officials

• Director Clinical Development

  Daiichi Sankyo

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2008
• First Posted: January 29, 2008
• Study Start: January 1, 2008
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: September 16, 2020
• Results First Posted: September 16, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• 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.
• 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.

Locations

US (10)