Abdominal NeoplasmPhase 2NCT00004547
Treatment of Peritoneal Cancer With Surgery, Perfused Heated Cisplatin and Chemotherapy
A Phase 2 study testing Surgery, Continuous hyperthermic peritoneal perfusion (CHPP) with Cisplatin and Postoperative dwell with paclitaxel and 5-FU in people with Abdominal Neoplasm and Colonic Neoplasm, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Abdominal Neoplasm, Colonic Neoplasm, Mesothelioma
- What is being tested?
- Surgery, Continuous hyperthermic peritoneal perfusion (CHPP) with Cisplatin and Postoperative dwell with paclitaxel and 5-FU
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 188 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2000to Aug 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Phase II Trial of Continuous Hyperthermic Peritoneal Perfusion (CHPP) With Cisplatin Plus Early Postoperative Intraperitoneal Paclitaxel and 5-Fluorouracil for Peritoneal Carcinomatosis
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.
Read more
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.
Read the 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).
- Being tested
- Surgery, Continuous hyperthermic peritoneal perfusion (CHPP) with Cisplatin, Postoperative dwell with paclitaxel and 5-FU
- Keywords
- Surgery, Mesothelioma, Pseudomyxoma, Colon Cancer, Chemotherapy
- Medical subject headings
- Abdominal Neoplasms, Colonic Neoplasms, Mesothelioma, Peritoneal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SurgeryProcedure or surgery
Also called Cytoreductive 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.
Continuous hyperthermic peritoneal perfusion (CHPP) with CisplatinProcedure or surgery
Also called Platinol, Cisplatinum
Postoperative dwell with paclitaxel and 5-FUDrug
Also called 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.
| Study group | Role | What they receive |
|---|---|---|
| Peritoneal mesothelioma | Experimental | 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. Receives: Procedure: Surgery; Procedure: Continuous hyperthermic peritoneal perfusion (CHPP) with Cisplatin; Drug: Postoperative dwell with paclitaxel and 5-FU |
| Low grade mucinous adenocarcinoma | Experimental | 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. Receives: Procedure: Surgery; Procedure: Continuous hyperthermic peritoneal perfusion (CHPP) with Cisplatin; Drug: Postoperative dwell with paclitaxel and 5-FU |
| Adenocarcinoma of gastrointestinal origin | Experimental | 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. Receives: Procedure: Surgery; Procedure: Continuous hyperthermic peritoneal perfusion (CHPP) with Cisplatin; Drug: Postoperative dwell with paclitaxel and 5-FU |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Disease-free Survival
Participants who achieve either a six or twelve month disease free interval based on radiographic imaging and symptoms.
Measured: On study date until the first scan with imageable disease, assessed up to 100 months or more.
Number of Participants With a Response
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.
Measured: Patients were assessed every three months for one year and then every 6 months
Number of Participants With Adverse Events
Here are the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.
Measured: only assessed during the perioperative period (i.e. up to 90 days following surgery)
Secondary outcomes (3)
Percentage of Participants Who Had Paclitaxel and 5-fluorouracil (5-FU) Analysis Performed
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).
Measured: Perioperative day 7-12 after surgery
Quality of Life Questionnaire Score
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.
Measured: 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
Signal Transduction Pathways in Tumor Tissue Versus Normal Tissue
Signal transduction pathways were measured using reverse phase protein lysate microarray to determine if the pathways are distinct in tumor versus normal tissue.
Measured: once during surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2000 (estimated)
- Study startJan 2000
- Primary completionAug 2009
- Study completionAug 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Abdominal NeoplasmStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 188 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Marybeth Hughes, M.D., National Institutes of Health Clinical Center (CC)
- Investigators
- Marybeth S Hughes, M.D., Principal investigator, National Cancer Institute, National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00004547
- Sponsor's protocol ID
- 000069
- Other IDs
- 00-C-0069
- Status last verified
- Sep 2015
- First submitted
- 3 Feb 2000
- Last updated
- 18 Nov 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
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.
PubMed 626987
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Continuous Hyperthermic Peritoneal Perfusion (CHPP) With Cisplatin Plus Early Postoperative Intraperitoneal Paclitaxel and 5-Fluorouracil for Peritoneal Carcinomatosis
- ClinicalTrials.gov ID
- NCT00004547
- Acronym / sponsor ID
- 000069
- Keywords
- Surgery, Mesothelioma, Pseudomyxoma, Colon Cancer, Chemotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 188 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jan 2000
- Primary completion
- Aug 2009 (actual)
- Study completion
- Aug 2009 (actual)
- First posted
- 4 Feb 2000 (estimated)
- Results
- Posted 22 Nov 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Peritoneal mesothelioma | Experimental | Procedure: Surgery, Procedure: Continuous hyperthermic peritoneal perfusion (CHPP) with Cisplatin, Drug: Postoperative dwell with paclitaxel and 5-FUPatients 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 | Experimental | Procedure: Surgery, Procedure: Continuous hyperthermic peritoneal perfusion (CHPP) with Cisplatin, Drug: Postoperative dwell with paclitaxel and 5-FULow 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 | Experimental | Procedure: Surgery, Procedure: Continuous hyperthermic peritoneal perfusion (CHPP) with Cisplatin, Drug: Postoperative dwell with paclitaxel and 5-FUAdenocarcinoma 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SurgeryAlso: Cytoreductive surgeryPatients 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. | Procedure or surgery | Adenocarcinoma of gastrointestinal origin, Low grade mucinous adenocarcinoma, Peritoneal mesothelioma |
| Continuous hyperthermic peritoneal perfusion (CHPP) with CisplatinAlso: Platinol, Cisplatinum | Procedure or surgery | Adenocarcinoma of gastrointestinal origin, Low grade mucinous adenocarcinoma, Peritoneal mesothelioma |
| Postoperative dwell with paclitaxel and 5-FUAlso: 5-FUIntraperitoneal 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. | Drug | Adenocarcinoma of gastrointestinal origin, Low grade mucinous adenocarcinoma, Peritoneal mesothelioma |
Primary outcome
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.
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
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)
Here are the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.
3 secondary outcomes
Percentage of Participants Who Had Paclitaxel and 5-fluorouracil (5-FU) Analysis Performed
Time frame: Perioperative day 7-12 after surgery
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
Signal Transduction Pathways in Tumor Tissue Versus Normal Tissue
Time frame: once during surgery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 626987Dedrick 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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Medline PlusLink provided by the sponsor.
- Drug InformationLink provided by the sponsor.
- US FDA ResourcesLink provided by the sponsor.
Related trials for Abdominal Neoplasm
RecruitingPhase 2
Investigation of Ubamatamab Combination Therapy in Adult Participants With Platinum-Resistant Ovarian Cancer
Ovarian Cancer, Fallopian Tube Cancer
Not yet recruiting
Nurse-Led Prehabilitation Before Major Abdominal Cancer Surgery
Colorectal Cancer
RecruitingPhase 1
Study of Preoperative Radiation Therapy in Participants With Resectable Recurrent Abdominal Adrenocortical Carcinoma
Adrenocortical Carcinoma (ACC), Recurrent Adrenocortical Carcinoma (ACC)
RecruitingPhase 1
Individual Response to Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Treatment of Peritoneal Carcinomatosis From Peritoneal Mesothelioma or Atypical Mesothelial Proliferation or From Ovarian, Colorectal, or Appendiceal Histologies
Peritoneal Mesothelioma, Peritoneal Carcinomatosis
RecruitingPhase 3
A Three-Part Phase 3 Study of Sofetabart Mipitecan in Participants With Platinum-Resistant (Part A) and Platinum-Sensitive (Parts B and C) Ovarian Cancer
Ovarian Neoplasms, Fallopian Tube Neoplasms
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marybeth S Hughes, M.D. principal investigator
National Cancer Institute, National Institutes of Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Surgery, Continuous hyperthermic peritoneal perfusion (CHPP) with Cisplatin and Postoperative dwell with paclitaxel and 5-FU in people with Abdominal Neoplasm and Colonic Neoplasm, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Nov 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00004547, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2015.