Treatment of Peritoneal Cancer With Surgery, Perfused Heated Cisplatin and Chemotherapy
| Status: | Completed |
|---|---|
| Conditions: | Lung Cancer, Colorectal Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/21/2016 |
| Start Date: | January 2000 |
| End Date: | August 2009 |
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.
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.
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.
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).
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).
- 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.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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