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Treatment of Peritoneal Cancer With Surgery, Perfused Heated Cisplatin and Chemotherapy

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00004547
First received: February 3, 2000
Last updated: July 23, 2012
Last verified: November 2011
  Purpose

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.


Condition Intervention Phase
Abdominal Neoplasm
Colonic Neoplasm
Mesothelioma
Peritoneal Neoplasm
Procedure: Surgery
Procedure: Continuous hyperthermic peritoneal perfusion (CHPP) with Cisplatin
Drug: Postoperative dwell with paclitaxel and 5-FU
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Continuous Hyperthermic Peritoneal Perfusion (CHPP) With Cisplatin Plus Early Postoperative Intraperitoneal Paclitaxel and 5-Fluorouracil for Peritoneal Carcinomatosis

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Number of Participants With Disease-free Survival [ Time Frame: On study date until the first scan with imageable disease, assessed up to 100 months or more. ] [ Designated as safety issue: No ]
    Participants who achieve either a six or twelve month disease free interval based on radiographic imaging and symptoms.

  • Number of Participants With a Response [ Time Frame: Patients were assessed every three months for one year and then every 6 months ] [ Designated as safety issue: No ]
    Response is assessed by measuring the time to clinical or radiographic recurrence of disease. Patients will be followed with computed tomography (CT) scans. At any time point where there is evidence of progressive disease in the peritoneal cavity (imageable tumor nodules or new onset of ascites) the patients will be scored as failing within the abdominal cavity.

  • Number of Participants With Adverse Events [ Time Frame: only assessed during the perioperative period (i.e. up to 90 days following surgery) ] [ Designated as safety issue: No ]
    Here are the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.


Secondary Outcome Measures:
  • Percentage of Participants Who Had Paclitaxel and 5-fluorouracil (5-FU) Analysis Performed [ Time Frame: Perioperative day 7-12 after surgery ] [ Designated as safety issue: No ]
    Paclitaxel and 5-FU levels in plasma and perfusate will be determined by standard high-performance liquid chromatography (HPLC). Samples will be collected just prior to (Time 0) the infusion of the intraperitoneal dwell of 5-FU and paclitaxel, at the following time intervals after the conclusion of the intraperitoneal dwell infusion (15 minutes, 1 hour, 6 hour, 12 hour, 24 hour, 48 hour).

  • Quality of Life Questionnaire Score [ Time Frame: preop, 6 weeks postop and then 3, 6, 9, and 12 months the first year and then every 6 months until the patient is off study ] [ Designated as safety issue: No ]

    The Short-Form-36 Health Survey (SF-36) and the Functional Assessment of Cancer Therapy Disease Specific for Colorectal Cancer (FACT-C) will be given to the patients upon admission preoperatively, then 6 weeks postoperatively, and then 3, 6, 9, and 12 months for the first year and then every 6 months until the patient goes off study. These forms summarize a participants positive and negative aspects that characterize one's psychological (emotional(, physical, and social well-being at a point in time.

    For detailed information about the questionnaires, please see the Protocol Link module.


  • Signal Transduction Pathways in Tumor Tissue Versus Normal Tissue [ Time Frame: once during surgery ] [ Designated as safety issue: No ]
    Signal transduction pathways were measured using reverse phase protein lysate microarray to determine if the pathways are distinct in tumor versus normal tissue.


Enrollment: 188
Study Start Date: January 2000
Study Completion Date: August 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Peritoneal mesothelioma
Patients with peritoneal mesothelioma suffer with intractable ascites but have a very surface oriented tumor which usually does not invade into organs and cause organ dysfunction. The main source of symptoms and cause of death is intractable ascites.
Procedure: Surgery
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.
Other Name: Cytoreductive surgery
Procedure: Continuous hyperthermic peritoneal perfusion (CHPP) with Cisplatin
Other Names:
  • Platinol
  • Cisplatinum
Drug: Postoperative dwell with paclitaxel and 5-FU
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.
Other Name: 5-FU
Experimental: Low grade mucinous adenocarcinoma
Low grade mucinous adenocarcinoma also includes low grade mucinous neoplasms of borderline malignant potential. Patients with low grade mucinous adenocarcinoma can have prolonged survival with debulking surgery alone. The majority of patients with truly malignant disease will die of complications from intraperitoneal progression of tumor within 2 to 5 years. The tumors are often surface oriented within the peritoneal cavity without metastases to other distant sites. The most common origin for this type of tumor is the appendix and ovary.
Procedure: Surgery
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.
Other Name: Cytoreductive surgery
Procedure: Continuous hyperthermic peritoneal perfusion (CHPP) with Cisplatin
Other Names:
  • Platinol
  • Cisplatinum
Drug: Postoperative dwell with paclitaxel and 5-FU
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.
Other Name: 5-FU
Experimental: Adenocarcinoma of gastrointestinal origin
Adenocarcinoma of gastrointestinal origin also includes other than low grade mucinous. Aggressive gastrointestinal adenocarcinomas such as gastric, small bowel, and colon cancer , tend to be more invasive into tissues and can more readily metastasize to distant sites. The cause of death is usually directly related to intraperitoneal progression of tumor. It is a more difficult group of patients to treat with intraperitoneal therapy because of the aggressive and invasive nature of the tumors.
Procedure: Surgery
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.
Other Name: Cytoreductive surgery
Procedure: Continuous hyperthermic peritoneal perfusion (CHPP) with Cisplatin
Other Names:
  • Platinol
  • Cisplatinum
Drug: Postoperative dwell with paclitaxel and 5-FU
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.
Other Name: 5-FU

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00004547

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Marybeth S Hughes, M.D. National Cancer Institute, National Institutes of Health
  More Information

Additional Information:
Publications:
Responsible Party: Marybeth S. Hughes, M.D./National Cancer Institute, National Institutes of Health
ClinicalTrials.gov Identifier: NCT00004547     History of Changes
Obsolete Identifiers: NCT00020059
Other Study ID Numbers: 000069, 00-C-0069
Study First Received: February 3, 2000
Results First Received: August 30, 2011
Last Updated: July 23, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Surgery
Mesothelioma
Pseudomyxoma
Colon Cancer
Chemotherapy

Additional relevant MeSH terms:
Abdominal Neoplasms
Colonic Neoplasms
Mesothelioma
Neoplasms
Neoplasms, Mesothelial
Peritoneal Neoplasms
Adenoma
Colonic Diseases
Colorectal Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Peritoneal Diseases
Cisplatin
Paclitaxel
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on November 25, 2014