This study will test the effectiveness of an experimental treatment for peritoneal cancer involving surgical removal of the tumor, perfusion of the abdomen during surgery with a heated solution of the drug cisplatin, and post-surgery combination chemotherapy in the abdomen with fluorouracil (5-FU) and paclitaxel.

Patients with certain peritoneal cancer whose tumors are confined to the abdomen may be eligible for this study. Candidates are screened with a medical history and physical examination, including blood tests, electrocardiogram and possibly bone scan, brain magnetic resonance imaging (MRI), and chest, abdomen and pelvic CT scans.

Participants undergo surgery to remove as much tumor as possible. Part of the intestines, pancreas, stomach or the entire spleen may also be removed if they are affected. During surgery, after the tumor has been removed, two catheters (thin plastic tubes) are placed in the abdomen. A chemotherapy solution containing the anti-cancer drug cisplatin heated to a temperature of about 108.6 degrees (10 degrees above normal body temperature) is then delivered into the abdomen through one catheter and drained through another. During treatment, a drug called sodium thiosulfate is given through a vein to reduce the risk of side effects of cisplatin, particularly kidney damage. After 90 minutes of bathing the abdomen with this solution, the drug is rinsed from the abdomen and the catheters removed. Another small catheter is then placed and left inside the abdomen with one end coming out through the skin. Seven to 12 days after the operation, the anti-cancer drugs 5-FU and paclitaxel are given through this catheter.

After complete recovery from the surgery, the catheter is removed and the patient is discharged from the hospital. Clinic visits are scheduled for periodic follow-up examination, imaging, and tests 3 and 6 months after surgery and every 6 months for up to 5 years as long as the disease does not worsen. Patients whose disease progresses are taken off the study and referred back to their local physician or referred for alternative care or other research studies.

Patients are also asked to assess how this therapy affects their general health and well being. This will require filling out two quality-of-life questionnaires before surgery and again at each follow-up visit after surgery. Each questionnaire takes about 15 minutes to complete.

Condition	Treatment or Intervention	Phase
Abdominal Neoplasm Colonic Neoplasm Mesothelioma Peritoneal Neoplasm	Procedure: Surgical tumor excision  Procedure: Abdominal perfusion  Drug: Cisplatin  Drug: 5-FU  Drug: Paclitaxel	Phase II

Further Study Details: 

Expected Total Enrollment:  169

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 with cisplatin plus early postoperative intraperitoneal dwell therapy with 5-FU and paclitaxel after cytoreductive surgery for peritoneal carcinomatosis. 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).

Genders Eligible for Study:  Both

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 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%.
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 FEV1 is less than 1.2 liters or their maximum voluntary ventilation is less than 50% 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 WBC is less than 3000/microliters or platelets are less than 75,000/mm(3).
Patients will be ineligible if the serum total bilirubin level or liver enzymes are greater than 2 times the upper limit of normal.
Patients who have failed previous intraperitoneal platinum therapy will be ineligible. Treatment failure is defined as radiographic evidence of disease progression on two consecutive CT scans within 6 months of treatment.
Pregnant women or women who are breast feeding will be ineligible.
Patients less than 30 kg will be ineligible.

Maryland
      National Cancer Institute (NCI), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  000069; 00-C-0069
Record last reviewed:  January 1, 2005
Last Updated:  February 14, 2005
Record first received:  February 3, 2000
ClinicalTrials.gov Identifier:  NCT00004547
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08