A Phase 1/2 Dose Finding Study of an Experimental New Drug CS7017, an Oral PPARγ Agonist Taken by Mouth Twice Daily in Combination With Paclitaxel Chemotherapy

• To determine the Phase 2 dose for CS-7017 co-administered with paclitaxel in subjects with advanced Anaplastic thyroid cancer [ Time Frame: until disease progression or the development of unacceptable toxicity ] [ Designated as safety issue: No ]
• To determine overall progression-free survival in combination with paclitaxel in subjects with advanced ATC [ Time Frame: until disease progression or the development of unacceptable toxicity ] [ Designated as safety issue: No ]

• To evaluate the safety profile of the combination of CS7017 and paclitaxel [ Time Frame: treatment continues until disease progression, unacceptable toxicity or consent withdrawal ] [ Designated as safety issue: No ]
• To determine the PK of CS7017 [ Time Frame: treatment continues until disease progression, unacceptable toxicity or consent withdrawal ] [ Designated as safety issue: No ]
• To determine the objective response rate [ Time Frame: treatment continues until disease progression, unacceptable toxicity or consent withdrawal ] [ Designated as safety issue: No ]
• To determine overall survival and median survival time [ Time Frame: treatment continues until disease progression, unacceptable toxicity or consent withdrawal ] [ Designated as safety issue: No ]

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.

• Drug: CS7017
  At Phase 1, CS-7017 will be tested in combination with paclitaxel at the following dosage levels: 0.15, 0.25, 0.35, and 0.50mg BID. At Phase 2, CS-7017 will be administered at the RP2D. Commercially available paclitaxel will be administrated as IV infusion over 3 hours once every 3 weeks.
• Drug: Paclitaxel

During the Phase 1 and Phase 2 portions of the study, subject eligibility criteria are identical except for prior treatment for ATC. During Phase 1, eligible subjects may have received prior chemotherapy while during Phase 2, eligible subjects 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
• Neither pregnant nor breastfeeding

Exclusion Criteria:

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