Phase I Hyperthermic Intraperitoneal Oxaliplatin for Peritoneal Malignancies
18 Years
N/A
Both
Peritoneal Cavity Cancer
Trial Information
Phase I Hyperthermic Intraperitoneal Oxaliplatin for Peritoneal Malignancies
OBJECTIVES:
Primary
- 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.
Secondary
- 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
genes.
- To assess tumor and normal tissue concentrations for total platinum obtained at
baseline and immediately after HIPC.
OUTLINE:
- 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.
Inclusion Criteria
Inclusion criteria:
- Patients must have histologic proof of peritoneal metastases (includes
adenomucinosis)
- Complete tumor resection possible (may include liver metastasis if treatable by
resection or radiofrequency ablation)
- Patients may have received previous chemotherapy (except peritoneal) and/or
immunotherapy. If previous chemotherapy, at least 4 weeks must have passed since last
dose.
- Patients may have received previous radiation therapy, however radiation to the large
bowel, small bowel and/or stomach will make the patient ineligible for this study.
- Patients must have a Karnofsky performance score of ≥ 80%.
- Adequate hematologic, renal and hepatic function within 14 days of registration
defined as:
- White blood count (WBC) ≥ 3,000
- platelet count ≥ 70,000,
- serum bilirubin ≤ 2.0 mg/dL,
- serum creatinine ≤ 1.5 mg/dL
- Patients must be at least 18 years of age
- Patients must be able to provide informed consent
Exclusion criteria:
- Metastatic disease is present outside the peritoneal cavity
- Diagnosis of mesothelioma
- Grade 2 or higher sensory neuropathy at time of study enrollment
- History of allergic reaction to platinum compounds
- Pregnant or lactating women. Pregnancy is a contraindication for receiving therapy,
thus where relevant, patients will be required to use effective birth control. The
agents used in this study include those which are pregnancy category D - clear
evidence of risk in pregnancy. There is no information on the excretion of agents
into breast milk therefore patients must refrain from breastfeeding while receiving
study therapy.
- Previous peritoneal chemotherapy.
- Patients with uncontrolled concurrent medical problems (i.e. diabetes mellitus) or
history of uncontrolled cardiovascular disease (no history of hospitalization for
acute myocardial infarction or congestive heart failure (CHF) within 3 months prior
to registration).
- Patients have psychiatric or addictive disorders that preclude obtaining informed
consent.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose of hyperthermic intraperitoneal oxaliplatin
Outcome Time Frame:
30 Days Post Treatment
Safety Issue:
Yes
Principal Investigator
Todd M. Tuttle, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Masonic Cancer Center, University of Minnesota
Authority:
United States: Food and Drug Administration
Study ID:
2005LS068
NCT ID:
NCT00625092
Start Date:
October 2007
Completion Date:
September 2011
Related Keywords:
- Peritoneal Cavity Cancer
- peritoneal cavity cancer
- Neoplasms
- Fever
- Peritoneal Neoplasms
Name | Location |
|---|---|
| Masonic Cancer Center, University of Minnesota | Minneapolis, Minnesota 55455 |
