title: Phase Ib Trial of Cabazitaxel and Tasquinimod in Men With Heavily Pretreated Metastatic Castration Resistant Prostate Cancer (mCRPC): The CATCH Trial.
abstract: Tasquinimod is an immunomodulating and anti-antiangiogenic oral agent with anti-prostate cancer activity in preclinical studies and in clinical trials of men with metastatic castration resistant prostate cancer (mCRPC), including single agent activity and in combination with taxanes. We sought to identify the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of tasquinimod in combination with cabazitaxel and prednisone in men with chemorefractory mCRPC.
  
  
  
  Men with mCRPC who had failed prior docetaxel chemotherapy received cabazitaxel 25 mg/m2every 3 weeks with oral tasquinimod at 1 of 3 escalating dose levels (0.25, 0.5, and 1.0 mg once daily) with prednisone and PEG-filgastrim support, using a 3 + 3 dose escalation design. Treatment continued until progressive disease or unacceptable toxicity.
  
  
  
  We enrolled 25 men with chemorefractory mCRPC. The RP2D was 0.5 mg tasquinimod based on excess DLTs (two of three men) observed at dose level 3 (1.0 mg) including grade 3 sensory neuropathy and grade 3 atrial fibrillation. Dose level 2 was expanded to 14 men, where 3 DLTs were observed: grade 3 fatigue, grade 4 febrile neutropenia, and grade 3 liver function abnormalities. The proportion of men with a ≥30% PSA decline was 63% and the median composite progression-free survival (PFS) was 8.5 months (95% CI 4.2-16.4 months) based on 12 PFS events. The median number of cycles of cabazitaxel was 6 (range 1-13), with six men receiving >10 cycles. Best overall RECIST responses (CR + PR) were observed in three men (12%), with stable disease in 12 (48%). No pharmacokinetic interactions were observed.
  
  
  
  We determined the RP2D of tasquinimod combined with cabazitaxel to be 0.5 mg daily following a 3 week lead-in of tasquinimod 0.25 mg with growth factor support. No unexpected toxicities occurred. Prostate 77: 385-395, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Divisions of Medical Oncology and Urology, Departments of Medicine and Surgery, Duke Cancer Institute, Durham, North Carolina.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Armstrong
authors.affiliation: Divisions of Medical Oncology and Urology, Departments of Medicine and Surgery, Duke Cancer Institute, Durham, North Carolina.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Humeniuk
authors.affiliation: Department of Biostatistics, Duke University, Durham, North Carolina.
authors.forename: Patrick
authors.initials: P
authors.lastname: Healy
authors.affiliation: Department of Medicine, University of Chicago, Chicago, Illinois.
authors.forename: Russell
authors.initials: R
authors.lastname: Szmulewitz
authors.affiliation: Divisions of Medical Oncology and Urology, Departments of Medicine and Surgery, Duke Cancer Institute, Durham, North Carolina.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Winters
authors.affiliation: Divisions of Medical Oncology and Urology, Departments of Medicine and Surgery, Duke Cancer Institute, Durham, North Carolina.
authors.forename: Julie
authors.initials: J
authors.lastname: Kephart
authors.affiliation: Divisions of Medical Oncology and Urology, Departments of Medicine and Surgery, Duke Cancer Institute, Durham, North Carolina.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Harrison
authors.affiliation: Department of Medicine, University of Chicago, Chicago, Illinois.
authors.forename: Elia
authors.initials: E
authors.lastname: Martinez
authors.affiliation: Divisions of Medical Oncology and Urology, Departments of Medicine and Surgery, Duke Cancer Institute, Durham, North Carolina.
authors.forename: Kelly
authors.initials: K
authors.lastname: Mundy
authors.affiliation: Department of Biostatistics, Duke University, Durham, North Carolina.
authors.forename: Susan
authors.initials: S
authors.lastname: Halabi
authors.affiliation: Divisions of Medical Oncology and Urology, Departments of Medicine and Surgery, Duke Cancer Institute, Durham, North Carolina.
authors.forename: Daniel
authors.initials: D
authors.lastname: George
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D018450:Disease Progression; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D064129:Prostatic Neoplasms, Castration-Resistant / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality; D015363:Quinolones / Q000008:administration & dosage*; D015996:Survival Rate / Q000639:trends; D043823:Taxoids / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D015363:Quinolones; D043823:Taxoids; C552428:cabazitaxel; C516109:tasquinimod
keywords: angiogenesis; cabazitaxel; chemotherapy; clinical trial; immunotherapy; mCRPC; phase I; prostate cancer; tasquinimod