A Phase II Trial of Aprinocarsen, an Antisense Oligonucleotide Inhibitor of Protein Kinase C α, Administered as a 21-Day Infusion to Patients with Advanced Ovarian Carcinoma

Ranjana Advani, Prema Peethambaram, Bert L. Luto, George A. Fisher, Lynn Hartmann, Harry J. Long, Joanne Halsey, Jon T. Holmlund, Andrew Dorr, Branimir I. Sikic

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Abstract

BACKGROUND. It has been postulated that protein kinase C α (PKC-α) plays a pivotal role in signal transduction in tumor cancer cells. Aprinocarsen, a 20-base antisense oligonucleotide, has shown ability to inhibit PKC-α protein expression and inhibit tumor growth in human xenograft models. In a previous Phase I trial, the authors demonstrated the safety and some evidence of activity in ovarian carcinoma of aprinocarsen administered as a 21-day, continuous, intravenous infusion. METHODS. In this Phase II trial, 36 patients with advanced ovarian carcinoma were treated with aprinocarsen at a dose of 2 mg/kg per day delivered as a 21-day, continuous, intravenous infusion. The primary objective was to determine the antitumor response, and the secondary objectives were to evaluate toxicity and to evaluate effects on quality of life (QOL). RESULTS. Between September 1997 and December 1999, 36 patients (median age, 58 years) were enrolled in this trial. Patients were stratified into 2 groups: a platinum-sensitive group (n = 12 patients) and a platinum-resistant group (n = 24 patients). All 36 patients were evaluable for toxicity, and 27 patients were fully assessable for antitumor response after 2 cycles of therapy. All patients had received prior treatments. No objective responses were noted in the platinum-sensitive group. In the platinum-resistant group, 1 patient had some evidence of antitumor activity indicated by a decrease in serum CA 125 and stable disease on imaging studies for 8 months. No changes were noted in overall patient ratings for any of the five QOL domains. CONCLUSIONS. When it was administered as a single agent, aprinocarsen did not have significant clinical activity in patients with advanced ovarian carcinoma. Further study may be warranted in combination with platinum-based regimens.

Original languageEnglish (US)
Pages (from-to)321-326
Number of pages6
JournalCancer
Volume100
Issue number2
DOIs
StatePublished - Jan 15 2004

Fingerprint

Antisense Oligonucleotides
Protein Kinase C
Carcinoma
Platinum
Intravenous Infusions
aprinocarsen
Quality of Life
Neoplasms
Heterografts
Signal Transduction
Safety

Keywords

  • Antisense oligonucleotides
  • Ovarian neoplasms
  • Phase II clinical trials
  • Protein kinase C

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

A Phase II Trial of Aprinocarsen, an Antisense Oligonucleotide Inhibitor of Protein Kinase C α, Administered as a 21-Day Infusion to Patients with Advanced Ovarian Carcinoma. / Advani, Ranjana; Peethambaram, Prema; Luto, Bert L.; Fisher, George A.; Hartmann, Lynn; Long, Harry J.; Halsey, Joanne; Holmlund, Jon T.; Dorr, Andrew; Sikic, Branimir I.

In: Cancer, Vol. 100, No. 2, 15.01.2004, p. 321-326.

Research output: Contribution to journalArticle

Advani, R, Peethambaram, P, Luto, BL, Fisher, GA, Hartmann, L, Long, HJ, Halsey, J, Holmlund, JT, Dorr, A & Sikic, BI 2004, 'A Phase II Trial of Aprinocarsen, an Antisense Oligonucleotide Inhibitor of Protein Kinase C α, Administered as a 21-Day Infusion to Patients with Advanced Ovarian Carcinoma', Cancer, vol. 100, no. 2, pp. 321-326. https://doi.org/10.1002/cncr.11909
Advani, Ranjana ; Peethambaram, Prema ; Luto, Bert L. ; Fisher, George A. ; Hartmann, Lynn ; Long, Harry J. ; Halsey, Joanne ; Holmlund, Jon T. ; Dorr, Andrew ; Sikic, Branimir I. / A Phase II Trial of Aprinocarsen, an Antisense Oligonucleotide Inhibitor of Protein Kinase C α, Administered as a 21-Day Infusion to Patients with Advanced Ovarian Carcinoma. In: Cancer. 2004 ; Vol. 100, No. 2. pp. 321-326.
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abstract = "BACKGROUND. It has been postulated that protein kinase C α (PKC-α) plays a pivotal role in signal transduction in tumor cancer cells. Aprinocarsen, a 20-base antisense oligonucleotide, has shown ability to inhibit PKC-α protein expression and inhibit tumor growth in human xenograft models. In a previous Phase I trial, the authors demonstrated the safety and some evidence of activity in ovarian carcinoma of aprinocarsen administered as a 21-day, continuous, intravenous infusion. METHODS. In this Phase II trial, 36 patients with advanced ovarian carcinoma were treated with aprinocarsen at a dose of 2 mg/kg per day delivered as a 21-day, continuous, intravenous infusion. The primary objective was to determine the antitumor response, and the secondary objectives were to evaluate toxicity and to evaluate effects on quality of life (QOL). RESULTS. Between September 1997 and December 1999, 36 patients (median age, 58 years) were enrolled in this trial. Patients were stratified into 2 groups: a platinum-sensitive group (n = 12 patients) and a platinum-resistant group (n = 24 patients). All 36 patients were evaluable for toxicity, and 27 patients were fully assessable for antitumor response after 2 cycles of therapy. All patients had received prior treatments. No objective responses were noted in the platinum-sensitive group. In the platinum-resistant group, 1 patient had some evidence of antitumor activity indicated by a decrease in serum CA 125 and stable disease on imaging studies for 8 months. No changes were noted in overall patient ratings for any of the five QOL domains. CONCLUSIONS. When it was administered as a single agent, aprinocarsen did not have significant clinical activity in patients with advanced ovarian carcinoma. Further study may be warranted in combination with platinum-based regimens.",
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T1 - A Phase II Trial of Aprinocarsen, an Antisense Oligonucleotide Inhibitor of Protein Kinase C α, Administered as a 21-Day Infusion to Patients with Advanced Ovarian Carcinoma

AU - Advani, Ranjana

AU - Peethambaram, Prema

AU - Luto, Bert L.

AU - Fisher, George A.

AU - Hartmann, Lynn

AU - Long, Harry J.

AU - Halsey, Joanne

AU - Holmlund, Jon T.

AU - Dorr, Andrew

AU - Sikic, Branimir I.

PY - 2004/1/15

Y1 - 2004/1/15

N2 - BACKGROUND. It has been postulated that protein kinase C α (PKC-α) plays a pivotal role in signal transduction in tumor cancer cells. Aprinocarsen, a 20-base antisense oligonucleotide, has shown ability to inhibit PKC-α protein expression and inhibit tumor growth in human xenograft models. In a previous Phase I trial, the authors demonstrated the safety and some evidence of activity in ovarian carcinoma of aprinocarsen administered as a 21-day, continuous, intravenous infusion. METHODS. In this Phase II trial, 36 patients with advanced ovarian carcinoma were treated with aprinocarsen at a dose of 2 mg/kg per day delivered as a 21-day, continuous, intravenous infusion. The primary objective was to determine the antitumor response, and the secondary objectives were to evaluate toxicity and to evaluate effects on quality of life (QOL). RESULTS. Between September 1997 and December 1999, 36 patients (median age, 58 years) were enrolled in this trial. Patients were stratified into 2 groups: a platinum-sensitive group (n = 12 patients) and a platinum-resistant group (n = 24 patients). All 36 patients were evaluable for toxicity, and 27 patients were fully assessable for antitumor response after 2 cycles of therapy. All patients had received prior treatments. No objective responses were noted in the platinum-sensitive group. In the platinum-resistant group, 1 patient had some evidence of antitumor activity indicated by a decrease in serum CA 125 and stable disease on imaging studies for 8 months. No changes were noted in overall patient ratings for any of the five QOL domains. CONCLUSIONS. When it was administered as a single agent, aprinocarsen did not have significant clinical activity in patients with advanced ovarian carcinoma. Further study may be warranted in combination with platinum-based regimens.

AB - BACKGROUND. It has been postulated that protein kinase C α (PKC-α) plays a pivotal role in signal transduction in tumor cancer cells. Aprinocarsen, a 20-base antisense oligonucleotide, has shown ability to inhibit PKC-α protein expression and inhibit tumor growth in human xenograft models. In a previous Phase I trial, the authors demonstrated the safety and some evidence of activity in ovarian carcinoma of aprinocarsen administered as a 21-day, continuous, intravenous infusion. METHODS. In this Phase II trial, 36 patients with advanced ovarian carcinoma were treated with aprinocarsen at a dose of 2 mg/kg per day delivered as a 21-day, continuous, intravenous infusion. The primary objective was to determine the antitumor response, and the secondary objectives were to evaluate toxicity and to evaluate effects on quality of life (QOL). RESULTS. Between September 1997 and December 1999, 36 patients (median age, 58 years) were enrolled in this trial. Patients were stratified into 2 groups: a platinum-sensitive group (n = 12 patients) and a platinum-resistant group (n = 24 patients). All 36 patients were evaluable for toxicity, and 27 patients were fully assessable for antitumor response after 2 cycles of therapy. All patients had received prior treatments. No objective responses were noted in the platinum-sensitive group. In the platinum-resistant group, 1 patient had some evidence of antitumor activity indicated by a decrease in serum CA 125 and stable disease on imaging studies for 8 months. No changes were noted in overall patient ratings for any of the five QOL domains. CONCLUSIONS. When it was administered as a single agent, aprinocarsen did not have significant clinical activity in patients with advanced ovarian carcinoma. Further study may be warranted in combination with platinum-based regimens.

KW - Antisense oligonucleotides

KW - Ovarian neoplasms

KW - Phase II clinical trials

KW - Protein kinase C

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