Phase I trial of a pathotropic retroviral vector expressing a cytocidal cyclin G1 construct (Rexin-G) in patients with advanced pancreatic cancer

Evanthia Galanis, Stephanie K Carlson, Nathan R. Foster, Val Lowe, Fernando Quevedo, Robert R Mc Williams, Axel F Grothey, Aminah Jatoi, Steven Robert Alberts, Joseph Rubin

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27 Citations (Scopus)

Abstract

Rexin-G is a pathotropic retroviral vector displaying a von Willebrand factor-targeting motif and expressing a dominant negative cyclin G1 gene. We undertook a phase I trial of intravenous (IV) administration of Rexin-G in patients with gemcitabine refractory, metastatic pancreatic adenocarcinoma. Twelve patients were treated. Dose escalation was performed from a dose of 1 × 1011 colony forming units (CFU) per cycle to 6 × 1011 CFU per cycle. The treatment was well tolerated. One dose-limiting toxicity (DLT) at dose level 2 (1.5 × 1011 CFU per cycle) was observed, consisting of grade 3 transaminitis. There was no detection of replication-competent virus in patients' peripheral blood mononuclear cells (PBMCs) or viral integration in DNA obtained from PBMCs, and no development of neutralizing antibodies. No evidence of antitumor activity was observed. The best objective response was progressive disease in 11 of the 12 study patients, while 1 patient showed radiographically stable disease with clinical deterioration and increase in the CA19.9 tumor marker. Median time to progression was 32 days. The median duration of survival of the study patients was 3.5 months from treatment initiation. Rexin-G is well tolerated in doses up to 6 × 1011 CFU in patients with recurrent pancreatic cancer, but there was no evidence of clinical antitumor activity.

Original languageEnglish (US)
Pages (from-to)979-984
Number of pages6
JournalMolecular Therapy
Volume16
Issue number5
DOIs
StatePublished - May 2008

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Cyclin G1
Pancreatic Neoplasms
Stem Cells
gemcitabine
Blood Cells
Virus Integration
von Willebrand Factor
Tumor Biomarkers
Virus Replication
Neutralizing Antibodies
Intravenous Administration
Adenocarcinoma
Survival
DNA

ASJC Scopus subject areas

  • Molecular Biology

Cite this

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title = "Phase I trial of a pathotropic retroviral vector expressing a cytocidal cyclin G1 construct (Rexin-G) in patients with advanced pancreatic cancer",
abstract = "Rexin-G is a pathotropic retroviral vector displaying a von Willebrand factor-targeting motif and expressing a dominant negative cyclin G1 gene. We undertook a phase I trial of intravenous (IV) administration of Rexin-G in patients with gemcitabine refractory, metastatic pancreatic adenocarcinoma. Twelve patients were treated. Dose escalation was performed from a dose of 1 × 1011 colony forming units (CFU) per cycle to 6 × 1011 CFU per cycle. The treatment was well tolerated. One dose-limiting toxicity (DLT) at dose level 2 (1.5 × 1011 CFU per cycle) was observed, consisting of grade 3 transaminitis. There was no detection of replication-competent virus in patients' peripheral blood mononuclear cells (PBMCs) or viral integration in DNA obtained from PBMCs, and no development of neutralizing antibodies. No evidence of antitumor activity was observed. The best objective response was progressive disease in 11 of the 12 study patients, while 1 patient showed radiographically stable disease with clinical deterioration and increase in the CA19.9 tumor marker. Median time to progression was 32 days. The median duration of survival of the study patients was 3.5 months from treatment initiation. Rexin-G is well tolerated in doses up to 6 × 1011 CFU in patients with recurrent pancreatic cancer, but there was no evidence of clinical antitumor activity.",
author = "Evanthia Galanis and Carlson, {Stephanie K} and Foster, {Nathan R.} and Val Lowe and Fernando Quevedo and {Mc Williams}, {Robert R} and Grothey, {Axel F} and Aminah Jatoi and Alberts, {Steven Robert} and Joseph Rubin",
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AU - Galanis, Evanthia

AU - Carlson, Stephanie K

AU - Foster, Nathan R.

AU - Lowe, Val

AU - Quevedo, Fernando

AU - Mc Williams, Robert R

AU - Grothey, Axel F

AU - Jatoi, Aminah

AU - Alberts, Steven Robert

AU - Rubin, Joseph

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