Phase I Hyperthermic Intraperitoneal Oxaliplatin for Peritoneal Malignancies
- To determine the safety and optimal dose of hyperthermic intraperitoneal oxaliplatin
when administered during cytoreductive surgery and followed by intraperitoneal
leucovorin calcium and fluorouracil in patients with peritoneal malignancies.
- To determine the outcome of cytoreductive surgery in these patients.
- To determine the time to disease progression and pattern of failure in patients treated
with this regimen.
- To determine the 1 and 5 year survival in patients treated with this regimen.
- To compare quality-of-life pre- and post-surgery in these patients.
- To characterize total- and free-platinum pharmacokinetics in the plasma and total
platinum in the intraperitoneal space at baseline, during, and after hyperthermic
intraperitoneal chemotherapy (HIPC).
- To assess for the presence of genetic polymorphisms in the XDP and XRCC1 DNA repair
- To assess tumor and normal tissue concentrations for total platinum obtained at
baseline and immediately after HIPC.
- Cytoreductive Surgery: Patients undergo an exploratory laparotomy to remove all tumor
nodules from all peritoneal surfaces prior to gastrointestinal anastomoses. An
intraperitoneal drain is placed for postoperative intraperitoneal chemotherapy.
- Hyperthermic peritoneal chemotherapy (HIPC): After cytoreductive surgery, but before
intestinal anastomosis, patients receive oxaliplatin into the abdomen cavity at
approximately 1 liter/min at 41-42º C and held for 30 minutes at the maximum tolerated
dose. A heat exchanger maintains the fluid temperature at 44-46º C to maintain the
intraperitoneal temperature at 41-42º C. Patients may receive fluid challenges,
furosemide, mannitol, or renal dose dopamine to maintain a brisk diuresis at the
discretion of the anesthesiologist.
- Intraperitoneal chemotherapy: After HIPC, patients receive leucovorin calcium
intraperitoneally through an intraperitoneal drain where it will remain for 2 hours and
then drained. Patients then receive fluorouracil intraperitoneally through the
intraperitoneal drain on day 1 and remain in the peritoneal fluid for 23 hours and then
drained. The infusion will be repeated on day 2.
Blood samples are collected prior to surgery for pharmacogenetic studies and analyzed for
the presence of genetic polymorphisms in the XPD and XRCC1 DNA repair genes and the GSTP1
and GSTM1 glutathione-S-transferase enzymes (i.e., XPD, Asp312Asn, XPD K751Q, XRCC1
Arg399GIn, XRCC1 Arg399Q, GSTP1 l105V, and GSTM1 DEL). Blood samples are also collected
periodically for pharmacokinetic studies and analyzed for oxaliplatin concentrations. Normal
and tumor tissue are collected periodically and analyzed for total platinum concentrations.
Quality of life is assessed at baseline and at 4, 8, and 12 months.
After completion of study treatment, patients are followed every 4 months for 2 years and
then every 6 months for at least 5 years.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of hyperthermic intraperitoneal oxaliplatin
30 Days Post Treatment
Todd M. Tuttle, MD
Masonic Cancer Center, University of Minnesota
United States: Food and Drug Administration
|Masonic Cancer Center, University of Minnesota||Minneapolis, Minnesota 55455|