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

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00004547
• Collaborator: (none)
• Enrollment: 188
• Location: 1
• Arms: 3
• Duration (Months): 115
• Patients Per Site Per Month: 1.6

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	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

Detailed Description

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).

Study Design

• Study Type: Interventional
• Actual Enrollment: 188 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (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
• Study Start Date: Jan 1, 2000
• Actual Primary Completion Date: Aug 1, 2009
• Actual Study Completion Date: Aug 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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 Names: 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 Names: 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 Names: 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 Names: 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 Names: 5-FU

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Disease-free Survival [On study date until the first scan with imageable disease, assessed up to 100 months or more.]

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

2. Number of Participants With a Response [Patients were assessed every three months for one year and then every 6 months]

   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.

3. Number of Participants With Adverse Events [only assessed during the perioperative period (i.e. up to 90 days following surgery)]

   Here are the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.

Secondary Outcome Measures

1. Percentage of Participants Who Had Paclitaxel and 5-fluorouracil (5-FU) Analysis Performed [Perioperative day 7-12 after surgery]

   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).

2. Quality of Life Questionnaire Score [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]

   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.

3. Signal Transduction Pathways in Tumor Tissue Versus Normal Tissue [once during surgery]

   Signal transduction pathways were measured using reverse phase protein lysate microarray to determine if the pathways are distinct in tumor versus normal tissue.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• 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

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Marybeth S Hughes, M.D., National Cancer Institute, National Institutes of Health

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page
• Medline Plus
• Drug Information
• US FDA Resources
• Short Form-36 Health Survey (SF-36)

Publications

• Dedrick RL, Myers CE, Bungay PM, DeVita VT Jr. Pharmacokinetic rationale for peritoneal drug administration in the treatment of ovarian cancer. Cancer Treat Rep. 1978 Jan;62(1):1-11.

• Responsible Party: Marybeth Hughes, M.D., Principal Investigator, National Institutes of Health Clinical Center (CC)
• ClinicalTrials.gov Identifier: NCT00004547
• Other Study ID Numbers: 000069; 00-C-0069; NCT00020059
• First Posted: Feb 4, 2000
• Last Update Posted: Nov 18, 2015
• Last Verified: Sep 1, 2015

• Keywords provided by Marybeth Hughes, M.D., Principal Investigator, National Institutes of Health Clinical Center (CC): Surgery; Mesothelioma; Pseudomyxoma; Colon Cancer; Chemotherapy
• Additional relevant MeSH terms: Neoplasms; Mesothelioma; Mesothelioma, Malignant; Colonic Neoplasms; Peritoneal Neoplasms; Abdominal Neoplasms; Paclitaxel; Cisplatin

Study Results

Participant Flow

Recruitment Details	A total accrual of 203 was expected within approximately 5-6 years (59 patients for adenocarcinoma of gastrointestinal origin, other than low grade mucinous; 48 patients with low grade mucinous adenocarcinoma; and 96 patients with primary peritoneal mesothelioma).

Arm/Group Title	Peritoneal Mesothelioma	Low Grade Mucinous Adenocarcinoma	Adenocarcinoma of Gastrointestinal Origin
Arm/Group Description	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.	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.	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.
Period Title: Overall Study
STARTED	83	48	57
Not Evaluable	21	9	23
COMPLETED	61	39	35
NOT COMPLETED	22	9	22

Baseline Characteristics

Arm/Group Title	Peritoneal Mesothelioma	Low Grade Mucinous Adenocarcinoma	Adenocarcinoma of Gastrointestinal Origin	Total
Arm/Group Description	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.	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.	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.	Total of all reporting groups
Overall Participants	83	48	57	188
Age (Count of Participants)
<=18 years	3 3.6%	0 0%	0 0%	3 1.6%
Between 18 and 65 years	71 85.5%	43 89.6%	52 91.2%	166 88.3%
>=65 years	9 10.8%	5 10.4%	5 8.8%	19 10.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.95 (14.12)	50.48 (10.85)	49.70 (11.78)	50.01 (12.61)
Sex: Female, Male (Count of Participants)
Female	38 45.8%	23 47.9%	28 49.1%	89 47.3%
Male	45 54.2%	25 52.1%	29 50.9%	99 52.7%
Race/Ethnicity, Customized (Number) [Number]
White	69 83.1%	38 79.2%	54 94.7%	161 85.6%
Hispanic	6 7.2%	0 0%	3 5.3%	9 4.8%
African American	2 2.4%	7 14.6%	0 0%	9 4.8%
Asian American	4 4.8%	3 6.3%	0 0%	7 3.7%
Unknown	2 2.4%	0 0%	0 0%	2 1.1%
Region of Enrollment (participants) [Number]
United States	83 100%	48 100%	57 100%	188 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Disease-free Survival
Description	Participants who achieve either a six or twelve month disease free interval based on radiographic imaging and symptoms.
Time Frame	On study date until the first scan with imageable disease, assessed up to 100 months or more.

Outcome Measure Data

Analysis Population Description

This outcome measure was not analyzed because information was not consistently available.

Arm/Group Title	Peritoneal Mesothelioma	Low Grade Mucinous Adenocarcinoma	Adenocarcinoma of Gastrointestinal Origin
Arm/Group Description	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.	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.	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.
Measure Participants	0	0	0

2. Primary Outcome

Title	Number of Participants With a Response
Description	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.
Time Frame	Patients were assessed every three months for one year and then every 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Peritoneal Mesothelioma	Low Grade Mucinous Adenocarcinoma	Adenocarcinoma of Gastrointestinal Origin
Arm/Group Description	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.	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.	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.
Measure Participants	83	48	57
Number [Participants]	24 28.9%	18 37.5%	6 10.5%

3. Primary Outcome

Title	Number of Participants With Adverse Events
Description	Here are the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.
Time Frame	only assessed during the perioperative period (i.e. up to 90 days following surgery)

Outcome Measure Data

Analysis Population Description

188 participants is consistent with the total number of participants analyzed (e.g. total from each column in participant flow, 83 P. Meso + 48 L. Grade + 57 Adeno. = 188).

Arm/Group Title	Mesothelioma, Low Grade, and Adenocarcinoma
Arm/Group Description	Patients with peritoneal mesothelioma suffer with intractable ascites. Patients with low grade mucinous adenocarcinoma can have prolonged survival with debulking surgery alone. 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.
Measure Participants	188
Number [Participants]	73 88%

4. Secondary Outcome

Title	Percentage of Participants Who Had Paclitaxel and 5-fluorouracil (5-FU) Analysis Performed
Description	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).
Time Frame	Perioperative day 7-12 after surgery

Outcome Measure Data

Analysis Population Description

This outcome measure was not analyzed because it was not feasible (e.g. inadequate samples).

Arm/Group Title	Peritoneal Mesothelioma	Low Grade Mucinous Adenocarcinoma	Adenocarcinoma of Gastrointestinal Origin
Arm/Group Description	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.	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.	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.
Measure Participants	0	0	0

5. Secondary Outcome

Title	Quality of Life Questionnaire Score
Description	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.
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

Outcome Measure Data

Analysis Population Description

This outcome measure was not evaluated due to poor patient compliance.

Arm/Group Title	Peritoneal Mesothelioma	Low Grade Mucinous Adenocarcinoma	Adenocarcinoma of Gastrointestinal Origin
Arm/Group Description	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.	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.	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.
Measure Participants	0	0	0

6. Secondary Outcome

Title	Signal Transduction Pathways in Tumor Tissue Versus Normal Tissue
Description	Signal transduction pathways were measured using reverse phase protein lysate microarray to determine if the pathways are distinct in tumor versus normal tissue.
Time Frame	once during surgery

Outcome Measure Data

Analysis Population Description

This outcome measure was not analyzed because it was not feasible.

Arm/Group Title	Normal Tissue	Tumor Tissue
Arm/Group Description	Non-diseased tissue	Diseased tissue
Measure Participants	0	0

Adverse Events

Adverse Event Reporting Description	Adverse Events: 188 participants is consistent with the total number of participants analyzed (e.g. total from each column in participant flow, 83 P.Meso + 48 L.Grade + 57 Adeno. = 188).
Arm/Group Title	Mesothelioma, Low Grade, and Adenocarcinoma
Arm/Group Description	Patients with peritoneal mesothelioma suffer with intractable ascites. Patients with low grade mucinous adenocarcinoma can have prolonged survival with debulking surgery alone. 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.
All Cause Mortality
	Mesothelioma, Low Grade, and Adenocarcinoma
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Mesothelioma, Low Grade, and Adenocarcinoma
	Affected / at Risk (%)	# Events
Total	71/188 (37.8%)
Cardiac disorders
atrial fibrillation	1/188 (0.5%)	1
Myocardial infarction	1/188 (0.5%)	1
Gastrointestinal disorders
ascites	2/188 (1.1%)	2
colitis	1/188 (0.5%)	1
colon perforation	2/188 (1.1%)	2
diarrhea	1/188 (0.5%)	1
Enterocutaneous fistula	2/188 (1.1%)	2
Gastric perforation	1/188 (0.5%)	1
Gastrointestinal (GI) perforation	1/188 (0.5%)	1
Ileus	2/188 (1.1%)	2
Nausea	4/188 (2.1%)	4
Pancreatic fistula	1/188 (0.5%)	1
Pancreatitis	3/188 (1.6%)	3
Perforated bowel	1/188 (0.5%)	1
Peritonitis	1/188 (0.5%)	1
Small bowel obstruction (sbo)	1/188 (0.5%)	1
Small bowel obstruction	12/188 (6.4%)	12
Hepatobiliary disorders
cholecystitis	1/188 (0.5%)	1
Thrombosis portal vein	1/188 (0.5%)	1
Infections and infestations
Neutropenic fever	5/188 (2.7%)	5
Sepsis	1/188 (0.5%)	1
Wound infection	7/188 (3.7%)	7
Psychiatric disorders
Hallucinations/post operative (op) psychosis	2/188 (1.1%)	2
Renal and urinary disorders
Renal failure	2/188 (1.1%)	2
Urinary tract infection	1/188 (0.5%)	1
Reproductive system and breast disorders
Pelvic abscess	1/188 (0.5%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism (PE)	3/188 (1.6%)	3
Pleural effusion	5/188 (2.7%)	5
Pneumothorax	1/188 (0.5%)	1
Stridor	1/188 (0.5%)	1
Voice changes	1/188 (0.5%)	1
Vascular disorders
Deep venous thrombosis (DVT)	1/188 (0.5%)	1
Thrombosis jugular	1/188 (0.5%)	1
Other (Not Including Serious) Adverse Events
	Mesothelioma, Low Grade, and Adenocarcinoma
	Affected / at Risk (%)	# Events
Total	2/188 (1.1%)
Cardiac disorders
Sinus ventricular tachycardia (SVT)	2/188 (1.1%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.