A randomized, double-blind, phase 2 trial of platinum therapy plus etoposide with or without concurrent vandetanib (ZD6474) in patients with previously untreated extensive-stage small cell lung cancer

Hoosier Cancer Research Network LUN06-113

Rachel E. Sanborn, Jyoti D. Patel, Gregory A. Masters, Nagesh Jayaram, Anthony Stephens, Michael Guarino, Jamal Misleh, Jingwei Wu, Nasser Hanna

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

BACKGROUND: This randomized, double-blind, phase 2 trial evaluated whether the addition of vandetanib to platinum plus etoposide for previously untreated extensive-stage small cell lung cancer (SCLC) prolonged the time to disease progression in comparison with chemotherapy alone. METHODS: Patients with previously untreated extensive-stage SCLC received platinum (cisplatin or carboplatin) with etoposide in combination with vandetanib (100mg daily) or a placebo for up to 4 total cycles (no maintenance therapy). An initial safety run-in phase was conducted with the first 6 patients enrolled; all these patients received vandetanib with cisplatin and etoposide. With an overall sample size of 68 patients, the study had 80% power to detect a 3-month difference in the time to progression (TTP) from 4 to 7 months (significance level,.10 [1-sided log-rank test]). RESULTS: Seventy-four patients were enrolled between April 2008 and May 2013. Thirty-three patients were ultimately randomized to each arm. The baseline characteristics were well balanced, and the median number of treatment cycles was 4 for each arm. Thirty-one patients in each arm were evaluable for TTP; the median TTP was 5.62 months with vandetanib and 5.68 months with the placebo (P=.9518). The median overall survival was 13.24 months with vandetanib and 9.23 months with the placebo (P=.4577; 33 evaluable patients in each arm). Nonhematologic toxicity was increased with vandetanib versus the placebo. No correlation was seen between vascular endothelial growth factor polymorphisms and outcomes. CONCLUSIONS: The addition of vandetanib to platinum and etoposide did not improve outcomes for patients with newly diagnosed extensive-stage SCLC. Toxicity was increased in comparison with chemotherapy alone.

Original languageEnglish (US)
JournalCancer
DOIs
StateAccepted/In press - 2016

Fingerprint

Small Cell Lung Carcinoma
Etoposide
Platinum
Research
Neoplasms
Placebos
Therapeutics
Cisplatin
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazolin-4-amine
Drug Therapy
Carboplatin
Sample Size
Vascular Endothelial Growth Factor A
Disease Progression
Safety
Survival

Keywords

  • Carboplatin
  • Cisplatin
  • Etoposide
  • Small cell lung cancer
  • Vandetanib

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

A randomized, double-blind, phase 2 trial of platinum therapy plus etoposide with or without concurrent vandetanib (ZD6474) in patients with previously untreated extensive-stage small cell lung cancer : Hoosier Cancer Research Network LUN06-113. / Sanborn, Rachel E.; Patel, Jyoti D.; Masters, Gregory A.; Jayaram, Nagesh; Stephens, Anthony; Guarino, Michael; Misleh, Jamal; Wu, Jingwei; Hanna, Nasser.

In: Cancer, 2016.

Research output: Contribution to journalArticle

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abstract = "BACKGROUND: This randomized, double-blind, phase 2 trial evaluated whether the addition of vandetanib to platinum plus etoposide for previously untreated extensive-stage small cell lung cancer (SCLC) prolonged the time to disease progression in comparison with chemotherapy alone. METHODS: Patients with previously untreated extensive-stage SCLC received platinum (cisplatin or carboplatin) with etoposide in combination with vandetanib (100mg daily) or a placebo for up to 4 total cycles (no maintenance therapy). An initial safety run-in phase was conducted with the first 6 patients enrolled; all these patients received vandetanib with cisplatin and etoposide. With an overall sample size of 68 patients, the study had 80{\%} power to detect a 3-month difference in the time to progression (TTP) from 4 to 7 months (significance level,.10 [1-sided log-rank test]). RESULTS: Seventy-four patients were enrolled between April 2008 and May 2013. Thirty-three patients were ultimately randomized to each arm. The baseline characteristics were well balanced, and the median number of treatment cycles was 4 for each arm. Thirty-one patients in each arm were evaluable for TTP; the median TTP was 5.62 months with vandetanib and 5.68 months with the placebo (P=.9518). The median overall survival was 13.24 months with vandetanib and 9.23 months with the placebo (P=.4577; 33 evaluable patients in each arm). Nonhematologic toxicity was increased with vandetanib versus the placebo. No correlation was seen between vascular endothelial growth factor polymorphisms and outcomes. CONCLUSIONS: The addition of vandetanib to platinum and etoposide did not improve outcomes for patients with newly diagnosed extensive-stage SCLC. Toxicity was increased in comparison with chemotherapy alone.",
keywords = "Carboplatin, Cisplatin, Etoposide, Small cell lung cancer, Vandetanib",
author = "Sanborn, {Rachel E.} and Patel, {Jyoti D.} and Masters, {Gregory A.} and Nagesh Jayaram and Anthony Stephens and Michael Guarino and Jamal Misleh and Jingwei Wu and Nasser Hanna",
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T1 - A randomized, double-blind, phase 2 trial of platinum therapy plus etoposide with or without concurrent vandetanib (ZD6474) in patients with previously untreated extensive-stage small cell lung cancer

T2 - Hoosier Cancer Research Network LUN06-113

AU - Sanborn, Rachel E.

AU - Patel, Jyoti D.

AU - Masters, Gregory A.

AU - Jayaram, Nagesh

AU - Stephens, Anthony

AU - Guarino, Michael

AU - Misleh, Jamal

AU - Wu, Jingwei

AU - Hanna, Nasser

PY - 2016

Y1 - 2016

N2 - BACKGROUND: This randomized, double-blind, phase 2 trial evaluated whether the addition of vandetanib to platinum plus etoposide for previously untreated extensive-stage small cell lung cancer (SCLC) prolonged the time to disease progression in comparison with chemotherapy alone. METHODS: Patients with previously untreated extensive-stage SCLC received platinum (cisplatin or carboplatin) with etoposide in combination with vandetanib (100mg daily) or a placebo for up to 4 total cycles (no maintenance therapy). An initial safety run-in phase was conducted with the first 6 patients enrolled; all these patients received vandetanib with cisplatin and etoposide. With an overall sample size of 68 patients, the study had 80% power to detect a 3-month difference in the time to progression (TTP) from 4 to 7 months (significance level,.10 [1-sided log-rank test]). RESULTS: Seventy-four patients were enrolled between April 2008 and May 2013. Thirty-three patients were ultimately randomized to each arm. The baseline characteristics were well balanced, and the median number of treatment cycles was 4 for each arm. Thirty-one patients in each arm were evaluable for TTP; the median TTP was 5.62 months with vandetanib and 5.68 months with the placebo (P=.9518). The median overall survival was 13.24 months with vandetanib and 9.23 months with the placebo (P=.4577; 33 evaluable patients in each arm). Nonhematologic toxicity was increased with vandetanib versus the placebo. No correlation was seen between vascular endothelial growth factor polymorphisms and outcomes. CONCLUSIONS: The addition of vandetanib to platinum and etoposide did not improve outcomes for patients with newly diagnosed extensive-stage SCLC. Toxicity was increased in comparison with chemotherapy alone.

AB - BACKGROUND: This randomized, double-blind, phase 2 trial evaluated whether the addition of vandetanib to platinum plus etoposide for previously untreated extensive-stage small cell lung cancer (SCLC) prolonged the time to disease progression in comparison with chemotherapy alone. METHODS: Patients with previously untreated extensive-stage SCLC received platinum (cisplatin or carboplatin) with etoposide in combination with vandetanib (100mg daily) or a placebo for up to 4 total cycles (no maintenance therapy). An initial safety run-in phase was conducted with the first 6 patients enrolled; all these patients received vandetanib with cisplatin and etoposide. With an overall sample size of 68 patients, the study had 80% power to detect a 3-month difference in the time to progression (TTP) from 4 to 7 months (significance level,.10 [1-sided log-rank test]). RESULTS: Seventy-four patients were enrolled between April 2008 and May 2013. Thirty-three patients were ultimately randomized to each arm. The baseline characteristics were well balanced, and the median number of treatment cycles was 4 for each arm. Thirty-one patients in each arm were evaluable for TTP; the median TTP was 5.62 months with vandetanib and 5.68 months with the placebo (P=.9518). The median overall survival was 13.24 months with vandetanib and 9.23 months with the placebo (P=.4577; 33 evaluable patients in each arm). Nonhematologic toxicity was increased with vandetanib versus the placebo. No correlation was seen between vascular endothelial growth factor polymorphisms and outcomes. CONCLUSIONS: The addition of vandetanib to platinum and etoposide did not improve outcomes for patients with newly diagnosed extensive-stage SCLC. Toxicity was increased in comparison with chemotherapy alone.

KW - Carboplatin

KW - Cisplatin

KW - Etoposide

KW - Small cell lung cancer

KW - Vandetanib

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DO - 10.1002/cncr.30287

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JO - Cancer

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