Phase i trial of AEG35156 an antisense oligonucleotide to xiap plus gemcitabine in patients with metastatic pancreatic ductal adenocarcinoma

Daruka Mahadevan, Pavani Chalasani, Diane Rensvold, Sandy Kurtin, Chris Pretzinger, Jacques Jolivet, Ramesh K. Ramanathan, Daniel D. Von Hoff, Glen J. Weiss

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

OBJECTIVES:: AEG35156 is an antisense oligonucleotide (ASO) that targets the X-linked inhibitor of apoptosis mRNA. Preclinical studies showed potent activity of AEG35156 in combination with gemcitabine in pancreatic ductal adenocarcinoma (PDA). A phase I study was conducted to establish the maximum-tolerated dose, safety, and antitumor activity of AEG35156 plus gemcitabine in metastatic PDA. METHODS:: Fourteen patients with metastatic PDA were enrolled. Nine patients were treated at 350 mg IV and 5 patients at 500 mg IV of AEG35156, 3 weeks on/1 week off of a 28-day cycle. Gemcitabine was administered at 1000 mg/m IV over 30 minutes immediately after AEG35156 in both groups. Because of perceived neurotoxicity dose deescalation to 350 mg was recommended. RESULTS:: All 14 patients were evaluable for tolerability and toxicity. Toxicities include neutropenia (grade 3/4, 6 patients), thrombocytopenia (grade 3, 2 patients), peripheral neuropathy (grade 3, 2 patients), fatigue (grade 3, 4 patients), ascites (grade 3, 2 patients), and nausea/vomiting (grade 4, 2 patients). Five patients (45%) experienced stable disease with a median progression-free survival of 58 days (95% CI, 52-107 d). CONCLUSIONS:: The maximum-tolerated dose is AEG35156 500 mg plus gemcitabine 1000 mg/m given on days 1, 8, and 15 every 28 days. AEG35156 plus gemcitabine failed to show significant clinical activity in advanced PDA.

Original languageEnglish (US)
Pages (from-to)239-243
Number of pages5
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Volume36
Issue number3
DOIs
StatePublished - Jun 2013

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gemcitabine
Antisense Oligonucleotides
Adenocarcinoma
Maximum Tolerated Dose
AEG 35156

Keywords

  • antisense oligonucleotide
  • dose-limiting toxicity
  • gemcitabine
  • maximum-tolerated dose
  • pancreas cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Phase i trial of AEG35156 an antisense oligonucleotide to xiap plus gemcitabine in patients with metastatic pancreatic ductal adenocarcinoma. / Mahadevan, Daruka; Chalasani, Pavani; Rensvold, Diane; Kurtin, Sandy; Pretzinger, Chris; Jolivet, Jacques; Ramanathan, Ramesh K.; Von Hoff, Daniel D.; Weiss, Glen J.

In: American Journal of Clinical Oncology: Cancer Clinical Trials, Vol. 36, No. 3, 06.2013, p. 239-243.

Research output: Contribution to journalArticle

Mahadevan, Daruka ; Chalasani, Pavani ; Rensvold, Diane ; Kurtin, Sandy ; Pretzinger, Chris ; Jolivet, Jacques ; Ramanathan, Ramesh K. ; Von Hoff, Daniel D. ; Weiss, Glen J. / Phase i trial of AEG35156 an antisense oligonucleotide to xiap plus gemcitabine in patients with metastatic pancreatic ductal adenocarcinoma. In: American Journal of Clinical Oncology: Cancer Clinical Trials. 2013 ; Vol. 36, No. 3. pp. 239-243.
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abstract = "OBJECTIVES:: AEG35156 is an antisense oligonucleotide (ASO) that targets the X-linked inhibitor of apoptosis mRNA. Preclinical studies showed potent activity of AEG35156 in combination with gemcitabine in pancreatic ductal adenocarcinoma (PDA). A phase I study was conducted to establish the maximum-tolerated dose, safety, and antitumor activity of AEG35156 plus gemcitabine in metastatic PDA. METHODS:: Fourteen patients with metastatic PDA were enrolled. Nine patients were treated at 350 mg IV and 5 patients at 500 mg IV of AEG35156, 3 weeks on/1 week off of a 28-day cycle. Gemcitabine was administered at 1000 mg/m IV over 30 minutes immediately after AEG35156 in both groups. Because of perceived neurotoxicity dose deescalation to 350 mg was recommended. RESULTS:: All 14 patients were evaluable for tolerability and toxicity. Toxicities include neutropenia (grade 3/4, 6 patients), thrombocytopenia (grade 3, 2 patients), peripheral neuropathy (grade 3, 2 patients), fatigue (grade 3, 4 patients), ascites (grade 3, 2 patients), and nausea/vomiting (grade 4, 2 patients). Five patients (45{\%}) experienced stable disease with a median progression-free survival of 58 days (95{\%} CI, 52-107 d). CONCLUSIONS:: The maximum-tolerated dose is AEG35156 500 mg plus gemcitabine 1000 mg/m given on days 1, 8, and 15 every 28 days. AEG35156 plus gemcitabine failed to show significant clinical activity in advanced PDA.",
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T1 - Phase i trial of AEG35156 an antisense oligonucleotide to xiap plus gemcitabine in patients with metastatic pancreatic ductal adenocarcinoma

AU - Mahadevan, Daruka

AU - Chalasani, Pavani

AU - Rensvold, Diane

AU - Kurtin, Sandy

AU - Pretzinger, Chris

AU - Jolivet, Jacques

AU - Ramanathan, Ramesh K.

AU - Von Hoff, Daniel D.

AU - Weiss, Glen J.

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N2 - OBJECTIVES:: AEG35156 is an antisense oligonucleotide (ASO) that targets the X-linked inhibitor of apoptosis mRNA. Preclinical studies showed potent activity of AEG35156 in combination with gemcitabine in pancreatic ductal adenocarcinoma (PDA). A phase I study was conducted to establish the maximum-tolerated dose, safety, and antitumor activity of AEG35156 plus gemcitabine in metastatic PDA. METHODS:: Fourteen patients with metastatic PDA were enrolled. Nine patients were treated at 350 mg IV and 5 patients at 500 mg IV of AEG35156, 3 weeks on/1 week off of a 28-day cycle. Gemcitabine was administered at 1000 mg/m IV over 30 minutes immediately after AEG35156 in both groups. Because of perceived neurotoxicity dose deescalation to 350 mg was recommended. RESULTS:: All 14 patients were evaluable for tolerability and toxicity. Toxicities include neutropenia (grade 3/4, 6 patients), thrombocytopenia (grade 3, 2 patients), peripheral neuropathy (grade 3, 2 patients), fatigue (grade 3, 4 patients), ascites (grade 3, 2 patients), and nausea/vomiting (grade 4, 2 patients). Five patients (45%) experienced stable disease with a median progression-free survival of 58 days (95% CI, 52-107 d). CONCLUSIONS:: The maximum-tolerated dose is AEG35156 500 mg plus gemcitabine 1000 mg/m given on days 1, 8, and 15 every 28 days. AEG35156 plus gemcitabine failed to show significant clinical activity in advanced PDA.

AB - OBJECTIVES:: AEG35156 is an antisense oligonucleotide (ASO) that targets the X-linked inhibitor of apoptosis mRNA. Preclinical studies showed potent activity of AEG35156 in combination with gemcitabine in pancreatic ductal adenocarcinoma (PDA). A phase I study was conducted to establish the maximum-tolerated dose, safety, and antitumor activity of AEG35156 plus gemcitabine in metastatic PDA. METHODS:: Fourteen patients with metastatic PDA were enrolled. Nine patients were treated at 350 mg IV and 5 patients at 500 mg IV of AEG35156, 3 weeks on/1 week off of a 28-day cycle. Gemcitabine was administered at 1000 mg/m IV over 30 minutes immediately after AEG35156 in both groups. Because of perceived neurotoxicity dose deescalation to 350 mg was recommended. RESULTS:: All 14 patients were evaluable for tolerability and toxicity. Toxicities include neutropenia (grade 3/4, 6 patients), thrombocytopenia (grade 3, 2 patients), peripheral neuropathy (grade 3, 2 patients), fatigue (grade 3, 4 patients), ascites (grade 3, 2 patients), and nausea/vomiting (grade 4, 2 patients). Five patients (45%) experienced stable disease with a median progression-free survival of 58 days (95% CI, 52-107 d). CONCLUSIONS:: The maximum-tolerated dose is AEG35156 500 mg plus gemcitabine 1000 mg/m given on days 1, 8, and 15 every 28 days. AEG35156 plus gemcitabine failed to show significant clinical activity in advanced PDA.

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KW - dose-limiting toxicity

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KW - maximum-tolerated dose

KW - pancreas cancer

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