Treatment of Peritoneal Cancer With Surgery, Perfused Heated Cisplatin and Chemotherapy
Condition: Abdominal Neoplasm; Colonic Neoplasm; Mesothelioma; Peritoneal Neoplasm
MeSH terms: Neoplasms; Mesothelioma; Mesothelioma, Malignant; Colonic Neoplasms; Peritoneal Neoplasms; Abdominal Neoplasms
Intervention: Surgery; Continuous hyperthermic peritoneal perfusion (CHPP) with Cisplatin; Postoperative dwell with paclitaxel and 5-FU
Intervention description: Patients will undergo cytoreductive 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.; Intraperitoneal dwell chemotherapy with a combination of 5-FU and Paclitaxel will be delivered in the early postoperative period (day 7 today 12 after surgery). Patients will be premedicated with hydrocortisone (100 mg/intravenous push (i.v.p.)), diphenhydramine (50 mg i.v.p.) and ranitidine (50 mg i.v.p.) 30 minutes prior to delivering intraperitoneal chemotherapy. One liter of normal saline will be infused containing 5-FU (800 mg/M^2) and 1 L of normal saline containing paclitaxel (125 mg/M^2) will be infused over 60 minutes. The chemotherapy solution will be left in the abdominal cavity permanently for slow absorption.
Intervention MeSH terms: Paclitaxel; Cisplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 188.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Surgery; Mesothelioma; Pseudomyxoma; Colon Cancer; Chemotherapy

Summary:

      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 (QOL) questionnaires before surgery
      and again at each follow-up visit after surgery. Each questionnaire takes about 15 minutes to
      complete.
    

Eligibility 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.