Debulking and Chemotherapy With or Without Intraperitoneal Chemotherapy to Treat Peritoneal Carcinomatosis
Condition: Gastrointestinal Neoplasm
MeSH terms: Carcinoma; Peritoneal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms
Intervention: Cytoreductive surgery; Continuous hyperthermic peritoneal perfusion (HIPEC/CHPP)
Intervention description: Patients will undergo a laparotomy, surgical incision in the abdomen to assess the peritoneal cavity with cytoreductive surgery or tumor debulking, to reduce tumor size.
Drug: Post operative chemotherapy: systemic oxaliplatin 85 mg/m^2 on day 1 only, leucovorin 200 mg/M^2/day on day 1, 2, 15, and 16, and infusional 5-flurouracil (5-FU) 800 mg/m^2 on day 8, every other week of every four weeks (two weeks per month) starting 4 to 6 weeks after operation and continuing for four cycles { 16 weeks total}.; Patients will undergo a laparotomy, surgical incision in the abdomen to assess the peritoneal cavity with cytoreductive surgery or tumor debulking, to reduce tumor size.
Followed by continuous hyperthermic peritoneal perfusion (HIPEC) with 250 mg/m^2 cisplatin. Post operative dwell chemotherapy given once between post op day 7 and 12: 5-fluororacil (5-FU) 800 mg/m^2 and paclitaxel 125 mg/m^2.
Drug: Post operative chemotherapy: systemic oxaliplatin 85 mg/m^2 on day 1 only, leucovorin 200 mg/M^2/day on day 1, 2, 15, and 16, and infusional 5-flurouracil (5-FU) 800 mg/m^2 on day 8, every other week of every four weeks (two weeks per month) starting 4 to 6 weeks after operation and continuing for four cycles { 16 weeks total}.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Appendiceal Cancer; Regional Therapy; Carcinomatosis; Hyperthermia

Summary:

      This study will determine which of the two following treatment regimens provides greater
      benefit to patients with peritoneal carcinomatosis (gastrointestinal cancer that has spread
      throughout the abdomen):

        -  Surgical removal of tumors plus heated chemotherapy during surgery, followed by one dose
           of chemotherapy 7 to 12 days after surgery, followed 3 weeks later by 4 months of
           chemotherapy; or

        -  Surgical removal of tumors followed by 4 months of chemotherapy, starting 1 month after
           surgery.

      Patients 18 years of age and older with peritoneal carcinomatosis may be eligible for this
      study. Candidates are screened with a medical history, physical examination, and blood tests;
      chest X-ray and computed tomography (CT) scans; review of pathology slides; electrocardiogram
      (EKG), bone scan, and brain magnetic resonance imaging (MRI), as needed; and laparotomy.
      Laparatomy is a surgical procedure in which an incision is made in the abdomen to look at the
      amount and location of tumors in the abdominal cavity. Patients whose surgery reveals that
      the tumors cannot be removed are taken off study. Those eligible for the study have their
      tumors removed during this screening laparotomy as part of the study procedure, as follows:

      All participants undergo laparotomy and removal of as much tumor as possible, as described
      above. Patients are then randomly assigned to one of two treatment groups:

        -  Group 1 - During laparotomy, after tumor removal, patients receive continuous
           hyperthermic peritoneal perfusion (CHPP) with the anti-cancer drug cisplatin. For CHPP,
           the cisplatin solution is heated and delivered to the abdomen through a catheter
           (plastic tube), washed through the abdomen for 90 minutes, and then drained out of the
           body through another catheter. At the close of surgery, a small catheter, called a
           Tenckhoff catheter, is left in the abdomen and brought out through the skin. Between
           days 7 and 12 after surgery, one dose of fluorouracil and paclitaxel chemotherapy is
           delivered through this catheter. The catheter is removed following complete recovery
           from surgery and the patient is discharged from the hospital. Four to 6 weeks after the
           surgery, patients have CT scans of the chest, pelvis, and abdomen, and then begin
           intravenous (IV, through a vein) chemotherapy with oxaliplatin, 5-fluorouracil (5-FU),
           and leucovorin. The chemotherapy is given in 4-week courses as follows: oxaliplatin on
           day 1, infused over 2 hours through a vein in the arm or neck; leucovorin on days 1 and
           2, infused over 2 hours, followed by 5-fluorouracil over 22 hours; leucovorin and 5-FU
           repeated two weeks later on days 15 and 16. This regimen is repeated two weeks later.
           Between each week of chemotherapy is a week break. A course of chemotherapy consists of
           28 days (two weeks of chemotherapy and two 1-week breaks). Patients may receive up to
           four courses (total of 16 weeks) unless their disease progresses or they cannot tolerate
           further doses. Doses of the chemotherapy can be reduced if the side effects are too
           severe.

        -  Group 2 - Patients follow the same procedure as those in Group 1 for laparotomy, CT
           imaging, and IV chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin. They do
           not receive CHPP or chemotherapy into the abdomen.

      All patients undergo repeat imaging tests six weeks after surgery and at the conclusion of
      the intravenous (IV) chemotherapy. They return for a physical examination and CT scans every
      three months for the first year, every four months for the next two years, and then every six
      months for up to five years after treatment. They are also asked to complete quality of life
      questionnaires before and after surgery, at the completion of chemotherapy, and at every
      follow-up visit.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               1. The patient must have histologically or cytologically proven peritoneal
                  carcinomatosis from low-grade mucinous adenocarcinoma of the gastrointestinal
                  tract. Patients with no tissue for examination may undergo percutaneous needle
                  aspiration under computed tomography (CT) or ultrasound guidance as clinically
                  indicated or a laparotomy with biopsy if a tumor grade cannot be determined on
                  other available material.

               2. Radiologic workup must demonstrate that there is no imageable disease outside of
                  the peritoneal cavity.

               3. Radiologic workup or prior abdominal exploration must show abnormalities
                  consistent with disease which can be debulked to a residual size of less than 1
                  cm in diameter per tumor deposit in the judgement of the investigators.

               4. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance
                  status of less than or equal to 2 on study entry and on the day prior to planned
                  treatment.

               5. Patients must have a minimum expected duration of survival of greater than 16
                  weeks.

               6. Patients must have recovered from any severe toxicity from all prior
                  chemotherapy, immunotherapy or radiotherapy except as outlined in appendix 1 of
                  the protocol and be at least 30 days past the date of their last treatment.

               7. 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..

               8. Patients must have a absolute neutrophil count (ANC) greater than
                  1,500/microliter.

               9. Patients must be age greater than or equal to 18 years.

        EXCLUSION CRITERIA:

          1. Patients will be excluded if they have concomitant medical problems that would place
             them at unacceptable risk for a major surgical procedure.

               1. Patients at increased risk for coronary artery disease or cardiac dysfunction
                  (e.g. age greater than 65, and a history of hypertension, first degree relative
                  with atherosclerotic coronary artery evaluation and will not be eligible if they
                  demonstrate significant irreversible ischemia on a stress thallium study or an
                  ejection fraction of less than 40%.

               2. Patients who have shortness of breath with minimal exertion or 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% of
                  expected.

          2. Patients who have a neurological toxicity of Grade 3 or greater will be excluded
             because of the potential neurotoxicity associated with platinum and paclitaxel
             therapy.

          3. Patients will be ineligible if they have a serum creatinine of greater than 1.5 mg/dL
             unless the measured creatinine clearance is greater than 60mL/min/1.73m^2.

          4. Patients will be ineligible if platelets are less than 75, 000/mm^3.

          5. Patients who have failed previous intraperitoneal chemotherapy will be ineligible.

          6. Pregnant women or women who are breast-feeding will be ineligible.

          7. Patients less than 30 kg will be ineligible.

          8. Patients who have undergone two or more operative procedures to debulk disease, have
             received 2 or more regimens of systemic chemotherapy, or any previous continuous
             hyperthermic peritoneal perfusion (CHPP) therapy will be excluded from study.