title: A Phase II Clinical Trial of CPI-613 in Patients with Relapsed or Refractory Small Cell Lung Carcinoma.
abstract: BACKGROUND
  Small cell lung cancer (SCLC) is a common lung cancer which presents with extensive stage disease at time of diagnosis in two-thirds of patients. For treatment of advanced disease, traditional platinum doublet chemotherapy induces response rates up to 80% but with few durable responses. CPI-613 is a novel anti-cancer agent that selectively inhibits the altered form of mitochondrial energy metabolism in tumor cells.
  
  
  METHODS
  We evaluated CPI-613 with a single-arm, open-label phase II study in patients with relapsed or refractory SCLC. CPI-613 was given at a dose of 3,000 mg/m2 on days 1 and 4 of weeks 1-3 of 4 week cycle. The primary outcome was response rate as assessed by CT imaging using RECIST v1.1 criteria. Secondary outcomes were progression-free survival (PFS), overall survival (OS), and toxicity. Twelve patients were accrued (median age 57yo) who had previously received between 1 and 4 lines of chemotherapy (median 1) for SCLC with a treatment-free interval of less than 60 days in 9 of the 12 patients.
  
  
  RESULTS
  No complete or partial responses were seen. Ten patients (83%) progressed as best response and 2 (17%) were not evaluable for response. Median time to progression was 1.7 months (range 0.7 to 1.8 months). Eleven patients (92%) died with median overall survival of 4.3 months (range 1.2 to 18.2 months). The study was closed early due to lack of efficacy. Of note, three out of three patients who progressed after CPI-613 and were subsequently treated with standard topotecan then demonstrated treatment response with survival for 18.2, 7.4, and 5.1 months. We conducted laboratory studies which found synergy in-vitro for CPI-613 with topotecan.
  
  
  CONCLUSIONS
  Single agent CPI-613 had no efficacy in this study. Further study of CPI 613 in combination with a topoisomerase inhibitor is warranted.
authors.affiliation: Department of Medicine, Section on Hematology and Oncology, Wake Forest School of Medicine, Winston-Salem, NC, United States of America.
authors.forename: Thomas W
authors.identifier: http://orcid.org/0000-0001-9475-1558
authors.initials: TW
authors.lastname: Lycan
authors.affiliation: Department of Medicine, Section on Hematology and Oncology, Wake Forest School of Medicine, Winston-Salem, NC, United States of America.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Pardee
authors.affiliation: Department of Medicine, Section on Hematology and Oncology, Wake Forest School of Medicine, Winston-Salem, NC, United States of America.
authors.forename: William J
authors.initials: WJ
authors.lastname: Petty
authors.affiliation: Department of Medicine, Section on Hematology and Oncology, Wake Forest School of Medicine, Winston-Salem, NC, United States of America.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Bonomi
authors.affiliation: Department of Medicine, Section on Hematology and Oncology, Wake Forest School of Medicine, Winston-Salem, NC, United States of America.
authors.forename: Angela
authors.initials: A
authors.lastname: Alistar
authors.affiliation: Department of Medicine, Section on Hematology and Oncology, Wake Forest School of Medicine, Winston-Salem, NC, United States of America.
authors.forename: Zanetta S
authors.initials: ZS
authors.lastname: Lamar
authors.affiliation: Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, United States of America.
authors.forename: Scott
authors.initials: S
authors.lastname: Isom
authors.affiliation: Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC, United States of America.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Chan
authors.affiliation: Department of Medicine, Section on Hematology and Oncology, Wake Forest School of Medicine, Winston-Salem, NC, United States of America.
authors.forename: Antonius A
authors.initials: AA
authors.lastname: Miller
authors.affiliation: Department of Medicine, Section on Hematology and Oncology, Wake Forest School of Medicine, Winston-Salem, NC, United States of America.|W.G. (Bill) Hefner Veteran Administration Medical Center, Cancer Center, Salisbury, NC, United States of America.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Ruiz
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D002210:Caprylates / Q000008:administration & dosage / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000473:pathology; D013440:Sulfides / Q000008:administration & dosage / Q000627:therapeutic use*; D059004:Topoisomerase I Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D019772:Topotecan / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D002210:Caprylates; D013440:Sulfides; D059004:Topoisomerase I Inhibitors; D019772:Topotecan; C568850:devimistat