Trial Information

Phase II Trial of Continuous Hyperthermic Peritoneal Perfusion (CHPP) With Cisplatin Plus Early Postoperative Intraperitoneal Paclitaxel and 5-Fluorouracil for Peritoneal Carcinomatosis

Background:

Cytoreductive surgery plus aggressive combination intraperitoneal chemotherapy may
significantly alter the natural history of peritoneal carcinomatosis. The purpose of this
study is to examine the treatment results of continuous hyperthermic peritoneal perfusion
(CHPP) with cisplatin plus early postoperative intraperitoneal dwell therapy with 5-FU and
paclitaxel after cytoreductive surgery for peritoneal carcinomatosis.

Objectives:

The primary objective of this study is to determine response and survival after continuous
hyperthermic peritoneal perfusion with cisplatin and early postoperative intraperitoneal
dwell therapy with 5-FU and paclitaxel. Response can only be assessed by measuring the time
to clinical or radiographic recurrence of disease.

The secondary objectives include the determination of pharmacokinetics of paclitaxel and
5-FU delivered into the peritoneal cavity and the impact that continuous hyperthermic
peritoneal perfusion with cisplatin and early postoperative intraperitoneal dwell therapy
with 5-FU and paclitaxel has on patients' health related quality of life.

The evaluation of pure populations of tumor and normal mesothelial cells to

- determine if signal transduction pathways are distinct in tumor versus normal tissue

- to see if specific cell pathways are activated or inhibited as a consequence of
therapy.

- to validate that this technology can provide informative data about these events as a
potential surrogate for clinical benefit from therapy or biological behavior of the
tumor.

Eligibility:

The patient greater than or equal to 30 kg must have histologically proven peritoneal
carcinomatosis from one of the following histologies: 1) primary peritoneal mesothelioma; 2)
low grade mucinous adenocarcinoma (including low grade mucinous neoplasms of borderline
malignant potential); 3) adenocarcinoma of gastrointestinal tract origin (other than low
grade mucinous, excluding pancreatic cancer), with disease confined to the peritoneal
cavity. Patients may not have had treatment for their disease within the previous 30 days
and have recovered from all toxicity. Patients must meet certain safety laboratory criteria
and may not have major medical disorders that would place them at unacceptable risk for a
major surgical procedure. Patients may not have received prior intraperitoneal platinum
therapy.

Design:

Patients will undergo cytoreductive surgery followed by CHPP with cisplatin. A peritoneal
dialysis catheter will be inserted into the peritoneal cavity at the time of laparotomy. In
the early postoperative period (day 2 - 10) intraperitoneal dwell chemotherapy with
paclitaxel (125 mg/M^2) and 5-FU (800 mg/M^2) will be administered. Patients will be seen 4
- 6 weeks after discharge for a physical examination and laboratory screen and QOL
evaluation. Tumor marker will be included at this stage. Patients will then be seen every
3 months for the first year after surgery and every 6 months thereafter. At each visit they
will undergo physical examination, laboratory screening (including tumor marker) and a CT
scan of the chest, abdomen and pelvis and QOL evaluation.

The objective of this pilot study is to estimate the ability of peritoneal perfusion to
achieve potentially tolerable disease free survival in patients with a variety of tumors.
For each class of tumors, an appropriate, distinct median disease free survival will be
targeted as the principal endpoint. The trial will be conducted as a set of three
single-stage phase II studies, with an early stopping rule for clearly unacceptable
outcomes. It is expected that accrual for 59 patients with adenocarcinoma of
gastrointestinal origin (other than low grade mucinous), 48 patients with low grade mucinous
adenocarcinoma, and 96 patients with primary peritoneal mesothelioma (total accrual of 203)
will require approximately 5 -6 years.

Results will be assessed by following the time to radiographic or clinical recurrence of
disease and survival. Patients will be stratified for entry based on histology. This will
include 3 cohorts: 1) peritoneal mesothelioma; 2) low grade mucinous adenocarcinoma
(including low grade mucinous neoplasms of borderline malignant potential); and 3)
adenocarcinoma of gastrointestinal origin (other than low grade mucinous).