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, Ramesk 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
Externally publishedYes

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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, Ramesk 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, Ramesk 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, Ramesk 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.

KW - antisense oligonucleotide

KW - dose-limiting toxicity

KW - gemcitabine

KW - maximum-tolerated dose

KW - pancreas cancer

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