Cabozantinib and Temozolomide for the Treatment of Unresectable or Metastatic Leiomyosarcoma or Other Soft Tissue Sarcoma

PRIMARY OBJECTIVE:

I. To determine the progression-free survival (defined as complete response \[CR\]+partial response \[PR\]+stable disease \[SD\]) assessed at 12 weeks for subjects in Cohort 1 (Leiomyosarcoma Arm) treated with cabozantinib and temozolomide as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

SECONDARY OBJECTIVES:

I. To determine the overall response rate (defined as CR+PR) for subjects in Cohort 1 treated with a combination of cabozantinib and temozolomide.

II. To determine the clinical benefit rate (CR+PR+SD) for subjects in Cohort 1 treated with a combination of cabozantinib and temozolomide.

III. To evaluate the median progression free rate for subjects with combination of cabozantinib and temozolomide.

IV. To evaluate overall survival for subjects in Cohort 1 treated with a combination of cabozantinib and temozolomide.

V. To assess safety and tolerability for subjects treated with a combination of cabozantinib and temozolomide.

VI. To determine the overall response rate (defined as CR+PR) in Cohort 2 (other soft tissue sarcomas).

VII. To assess Quality of Life (QoL) and subject-reported outcomes as measured by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) and the EuroQoL-Group Health Questionnaire (EQ-5D-5L).

EXPLORATORY OBJECTIVE:

I. To estimate the correlation of progression free rate (PFR) and overall survival (OS) to levels of sVEGFR2, PIGF, VEGF, HGF, sMET, VEGF-C, VEGF-D, and soluble AXL.

OUTLINE:

Patients receive cabozantinib orally (PO) once daily (QD) on days 1-28 and temozolomide PO QD on days 1-5. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients with progressive disease (PD) are followed up every 6 months for up to 2 years and patients without PD are followed up every 6 months for up to 5 years.