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

Study Overview
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Brief Summary
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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.

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

Conditions
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Anaplastic Thyroid Cancer

Intervention / Treatment
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* Drug: CS-7017
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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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)

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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1; 0.15 mg CS-7017<br>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<br>* 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).<br>Drug: Paclitaxel<br>* Commercially available paclitaxel will be administrated as IV infusion over 3 hours once every 3 weeks.<br>|
| Experimental: Cohort 2; 0.30 mg CS-7017<br>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<br>* 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).<br>Drug: Paclitaxel<br>* Commercially available paclitaxel will be administrated as IV infusion over 3 hours once every 3 weeks.<br>|
| Experimental: Cohort 3; 0.50 mg CS-7017<br>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<br>* 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).<br>Drug: Paclitaxel<br>* Commercially available paclitaxel will be administrated as IV infusion over 3 hours once every 3 weeks.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anaplastic Thyroid Cancer, Neoplasm, Tumor, Anti-neoplastic Agent, First-line treatment of advanced Anaplastic thyroid cancer