Talimogene Laherparepvec for the Treatment of Peritoneal Surface Malignancies
Condition: Stage IV Peritoneal Surface Dissemination From Gastrointestinal or Recurrent, Platinum-resistant Ovarian Cancer That Cannot be Completely Resected
MeSH terms: Peritoneal Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      The primary objective of this open-label, Phase I, trial is to evaluate the toxicity profile
      of intraperitoneal talimogene laherparepvec (TVEC) in patients with peritoneal surface
      dissemination from gastrointestinal or recurrent, platinum-resistant ovarian tumors. The
      secondary objectives are to evaluate the pharmacokinetic profile and viral shedding of TVEC
      by measuring viral load in serum and urine as well as viral load in peritoneal washings.
    

Detailed description: 
      This is a non-randomized, open-label Phase I trial in patients with Stage IV peritoneal
      surface dissemination from gastrointestinal or recurrent, platinum-resistant ovarian tumors
      enrolled at Duke Cancer Institute. All subjects will complete an extensive medical history,
      baseline physical examination and clinical assessment to ensure subject eligibility
      requirements within 4 weeks of starting study drug. All eligible patients must have a
      peritoneal catheter placed at least 2 weeks prior to the initiation of therapy. All patients
      will receive an initial loading dose of TVEC 4x106 Plaque Forming Units (PFU) on Cycle 1 Day
      1 to enable the formation of protective antibodies as described in the currently approved
      treatment protocol for the treatment of cutaneous melanoma. Three weeks after the initial
      loading dose, patients will receive TVEC at the dose level for the cohort for which they are
      enrolled every 2 weeks for up to 4 doses. The length of the first cycle is 5 weeks and
      subsequent cycles are 2 weeks in duration.

      The first portion of the study, the Dose Escalation cohort, will evaluate the toxicity
      profile of TVEC in patients with peritoneal surface dissemination from gastrointestinal or
      recurrent, platinum-resistant ovarian tumors. Using a standard '3+3' dose escalation design,
      there are up to three dose levels that may be explored. Dose escalation will be dependent on
      dose-limiting toxicity (DLT) within the cohorts.

      Once the MTD has been determined, an additional 6 subjects will be enrolled to the dose
      expansion cohort. All subjects will receive an initial loading dose of TVEC 4x106 PFU on
      Cycle 1 Day 1. Three weeks after the initial loading dose, patients will receive TVEC at the
      MTD every 2 weeks for up to 4 doses. The length of the first cycle is 5 weeks and the
      subsequent cycles are 2 weeks in duration. There are a total of four cycles.
    

Intervention name(s): Talimogene Laherparepvec
Intervention type(s): Biological
Intervention description(s): TVEC is an oncolytic, genetically modified virus designed to reproduce in tumor tissue and stimulate your immune system to attack the tumor cells
Other intervention name(s): (T-VEC)
Intervention MeSH terms: Talimogene laherparepvec
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment