A phase II clinical trial of cpi-613 in patients with relapsed or refractory small cell lung carcinoma

Thomas W. Lycan, Timothy S. Pardee, William J. Petty, Marcelo Bonomi, Angela Alistar, Zanetta S. Lamar, Scott Isom, Michael D. Chan, Antonius A. Miller, Jimmy Ruiz

Research output: Contribution to journalArticle

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Abstract

Backgroun Small cell lung cancer (SCLC) is a common lung cancer which presents with extensiv 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% bu with few durable responses. CPI-613 is a novel anti-cancer agent that selectively inhibit the altered form of mitochondrial energy metabolism in tumor cells Method We evaluated CPI-613 with a single-Arm, open-label phase II study in patients wit relapsed or refractory SCLC. CPI-613 was given at a dose of 3,000 mg/m2 on days 1 and of weeks 1-3 of 4 week cycle. The primary outcome was response rate as assessed by C imaging using RECIST v1.1 criteria. Secondary outcomes were progression-free surviva (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 SCL with a treatment-free interval of less than 60 days in 9 of the 12 patients Result No complete or partial responses were seen. Ten patients (83%) progressed as bes response and 2 (17%) were not evaluable for response. Median time to progression wa 1.7 months (range 0.7 to 1.8 months). Eleven patients (92%) died with median overall surviva of 4.3 months (range 1.2 to 18.2 months). The study was closed early due to lack o efficacy. Of note, three out of three patients who progressed after CPI-613 and were subsequentl treated with standard topotecan then demonstrated treatment response with surviva for 18.2, 7.4, and 5.1 months. We conducted laboratory studies which found synerg in-vitro for CPI-613 with topotecan Conclusion Single agent CPI-613 had no efficacy in this study. Further study of CPI 613 in combinatio with a topoisomerase inhibitor is warranted.

Original languageEnglish (US)
Article numbere0164244
JournalPLoS One
Volume11
Issue number10
DOIs
StatePublished - Oct 1 2016
Externally publishedYes

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Phase II Clinical Trials
Small Cell Lung Carcinoma
Refractory materials
carcinoma
clinical trials
lungs
Cells
lung neoplasms
Topotecan
cells
Chemotherapy
drug therapy
Topoisomerase Inhibitors
Drug Therapy
Wit and Humor
platinum
antineoplastic agents
CPI 613
Platinum
energy metabolism

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Lycan, T. W., Pardee, T. S., Petty, W. J., Bonomi, M., Alistar, A., Lamar, Z. S., ... Ruiz, J. (2016). A phase II clinical trial of cpi-613 in patients with relapsed or refractory small cell lung carcinoma. PLoS One, 11(10), [e0164244]. https://doi.org/10.1371/journal.pone.0164244
Lycan, Thomas W. ; Pardee, Timothy S. ; Petty, William J. ; Bonomi, Marcelo ; Alistar, Angela ; Lamar, Zanetta S. ; Isom, Scott ; Chan, Michael D. ; Miller, Antonius A. ; Ruiz, Jimmy. / A phase II clinical trial of cpi-613 in patients with relapsed or refractory small cell lung carcinoma. In: PLoS One. 2016 ; Vol. 11, No. 10.
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title = "A phase II clinical trial of cpi-613 in patients with relapsed or refractory small cell lung carcinoma",
abstract = "Backgroun Small cell lung cancer (SCLC) is a common lung cancer which presents with extensiv 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{\%} bu with few durable responses. CPI-613 is a novel anti-cancer agent that selectively inhibit the altered form of mitochondrial energy metabolism in tumor cells Method We evaluated CPI-613 with a single-Arm, open-label phase II study in patients wit relapsed or refractory SCLC. CPI-613 was given at a dose of 3,000 mg/m2 on days 1 and of weeks 1-3 of 4 week cycle. The primary outcome was response rate as assessed by C imaging using RECIST v1.1 criteria. Secondary outcomes were progression-free surviva (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 SCL with a treatment-free interval of less than 60 days in 9 of the 12 patients Result No complete or partial responses were seen. Ten patients (83{\%}) progressed as bes response and 2 (17{\%}) were not evaluable for response. Median time to progression wa 1.7 months (range 0.7 to 1.8 months). Eleven patients (92{\%}) died with median overall surviva of 4.3 months (range 1.2 to 18.2 months). The study was closed early due to lack o efficacy. Of note, three out of three patients who progressed after CPI-613 and were subsequentl treated with standard topotecan then demonstrated treatment response with surviva for 18.2, 7.4, and 5.1 months. We conducted laboratory studies which found synerg in-vitro for CPI-613 with topotecan Conclusion Single agent CPI-613 had no efficacy in this study. Further study of CPI 613 in combinatio with a topoisomerase inhibitor is warranted.",
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Lycan, TW, Pardee, TS, Petty, WJ, Bonomi, M, Alistar, A, Lamar, ZS, Isom, S, Chan, MD, Miller, AA & Ruiz, J 2016, 'A phase II clinical trial of cpi-613 in patients with relapsed or refractory small cell lung carcinoma', PLoS One, vol. 11, no. 10, e0164244. https://doi.org/10.1371/journal.pone.0164244

A phase II clinical trial of cpi-613 in patients with relapsed or refractory small cell lung carcinoma. / Lycan, Thomas W.; Pardee, Timothy S.; Petty, William J.; Bonomi, Marcelo; Alistar, Angela; Lamar, Zanetta S.; Isom, Scott; Chan, Michael D.; Miller, Antonius A.; Ruiz, Jimmy.

In: PLoS One, Vol. 11, No. 10, e0164244, 01.10.2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A phase II clinical trial of cpi-613 in patients with relapsed or refractory small cell lung carcinoma

AU - Lycan, Thomas W.

AU - Pardee, Timothy S.

AU - Petty, William J.

AU - Bonomi, Marcelo

AU - Alistar, Angela

AU - Lamar, Zanetta S.

AU - Isom, Scott

AU - Chan, Michael D.

AU - Miller, Antonius A.

AU - Ruiz, Jimmy

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Backgroun Small cell lung cancer (SCLC) is a common lung cancer which presents with extensiv 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% bu with few durable responses. CPI-613 is a novel anti-cancer agent that selectively inhibit the altered form of mitochondrial energy metabolism in tumor cells Method We evaluated CPI-613 with a single-Arm, open-label phase II study in patients wit relapsed or refractory SCLC. CPI-613 was given at a dose of 3,000 mg/m2 on days 1 and of weeks 1-3 of 4 week cycle. The primary outcome was response rate as assessed by C imaging using RECIST v1.1 criteria. Secondary outcomes were progression-free surviva (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 SCL with a treatment-free interval of less than 60 days in 9 of the 12 patients Result No complete or partial responses were seen. Ten patients (83%) progressed as bes response and 2 (17%) were not evaluable for response. Median time to progression wa 1.7 months (range 0.7 to 1.8 months). Eleven patients (92%) died with median overall surviva of 4.3 months (range 1.2 to 18.2 months). The study was closed early due to lack o efficacy. Of note, three out of three patients who progressed after CPI-613 and were subsequentl treated with standard topotecan then demonstrated treatment response with surviva for 18.2, 7.4, and 5.1 months. We conducted laboratory studies which found synerg in-vitro for CPI-613 with topotecan Conclusion Single agent CPI-613 had no efficacy in this study. Further study of CPI 613 in combinatio with a topoisomerase inhibitor is warranted.

AB - Backgroun Small cell lung cancer (SCLC) is a common lung cancer which presents with extensiv 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% bu with few durable responses. CPI-613 is a novel anti-cancer agent that selectively inhibit the altered form of mitochondrial energy metabolism in tumor cells Method We evaluated CPI-613 with a single-Arm, open-label phase II study in patients wit relapsed or refractory SCLC. CPI-613 was given at a dose of 3,000 mg/m2 on days 1 and of weeks 1-3 of 4 week cycle. The primary outcome was response rate as assessed by C imaging using RECIST v1.1 criteria. Secondary outcomes were progression-free surviva (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 SCL with a treatment-free interval of less than 60 days in 9 of the 12 patients Result No complete or partial responses were seen. Ten patients (83%) progressed as bes response and 2 (17%) were not evaluable for response. Median time to progression wa 1.7 months (range 0.7 to 1.8 months). Eleven patients (92%) died with median overall surviva of 4.3 months (range 1.2 to 18.2 months). The study was closed early due to lack o efficacy. Of note, three out of three patients who progressed after CPI-613 and were subsequentl treated with standard topotecan then demonstrated treatment response with surviva for 18.2, 7.4, and 5.1 months. We conducted laboratory studies which found synerg in-vitro for CPI-613 with topotecan Conclusion Single agent CPI-613 had no efficacy in this study. Further study of CPI 613 in combinatio with a topoisomerase inhibitor is warranted.

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