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


Phase 2
18 Years
N/A
Not Enrolling
Both
Abdominal Neoplasm, Colonic Neoplasm, Mesothelioma, Peritoneal Neoplasm

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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).

Inclusion Criteria


- INCLUSION CRITERIA:

The patient must have histologically proven peritoneal carcinomatosis from the following
histologies: primary peritoneal mesothelioma; low grade mucinous adenocarcinoma (including
low grade mucinous neoplasms of borderline malignant potential); adenocarcinoma of
gastrointestinal tract origin (other than low grade mucinous, excluding pancreatic
cancer).

Radiologic workup must demonstrate that the disease is confined to the peritoneal cavity.

Radiologic workup or prior abdominal exploration must be consistent with disease which can
be debulked to a residual size of less that 1 cm in diameter per tumor deposit.

Patients must have an Eastern Cooperative Onocology Group (ECOG) performance status of
less than or equal to 2.

Patients must have a minimum expected duration of survival of greater than 8 weeks.

Patients must have recovered from any toxicity from all prior chemotherapy, immunotherapy
or radiotherapy and be at least 30 days past the date of their last treatment.

EXCLUSION CRITERIA:

Patients will be excluded if they have concomitant medical problems that would place them
at unacceptable risk for a major surgical procedure.

Patients at increased risk for coronary artery disease or cardiac dysfunction (e.g., age
greater than 65, history of hypertension, first degree relative with atherosclerotic
coronary artery disease) will undergo cardiac evaluation and will not be eligible if they
demonstrate significant irreversible ischemia on a stress thallium study or an injection
fraction of less than 40 percent.

Patients who have shortness of breath with minimal exertion and who are at risk for
pulmonary disease (e.g., chronic smokers) will undergo pulmonary function testing and will
not be eligible if their forced expiratory volume 1 (FEV1) is less than 1.2 liters or
their maximum voluntary ventilation is less than 50 percent of expected.

Patients who have a baseline neurological toxicity of Grade 3 or greater will be excluded
because of the potential neurotoxicity associated with platinum and paclitaxel therapy.

Patients will be ineligible if they have a creatinine of greater than 1.5 or a creatinine
clearance of less 70 mL/min.

Patients will be ineligible if the white blood cell (WBC) is less than 3000/microliters or
platelets are less than 75,000mL/mm(3).

Patients must have a serum aspartate aminotransferase (AST) and alanine aminotransferase
(ALT) within 5 times the upper limit of normal and a total serum bilirubin of less than 3
times the upper limit of normal, both of which define the upper limit of grade 2 treatment
related toxicities.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Participants With Disease-free Survival

Outcome Description:

Participants who achieve either a six or twelve month disease free interval based on radiographic imaging and symptoms.

Outcome Time Frame:

On study date until the first scan with imageable disease, assessed up to 100 months or more.

Safety Issue:

No

Principal Investigator

Marybeth S Hughes, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute, National Institutes of Health

Authority:

United States: Federal Government

Study ID:

000069

NCT ID:

NCT00004547

Start Date:

January 2000

Completion Date:

August 2009

Related Keywords:

  • Abdominal Neoplasm
  • Colonic Neoplasm
  • Mesothelioma
  • Peritoneal Neoplasm
  • Surgery
  • Mesothelioma
  • Pseudomyxoma
  • Colon Cancer
  • Chemotherapy
  • Abdominal Neoplasms
  • Neoplasms
  • Colonic Neoplasms
  • Mesothelioma
  • Peritoneal Neoplasms

Name

Location

National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland  20892