Primary objective:- to study the safety, tolerability and feasibility of gastrectomy combined with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) after neoadjuvant systemic chemotherapy as primary treatment option for…
ID
Source
Brief title
Condition
- Malignant and unspecified neoplasms gastrointestinal NEC
- Gastrointestinal neoplasms malignant and unspecified
- Gastrointestinal therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Treatment related toxicity (graded according to the NCI Common Toxicity
Criteria version 4.0)
Secondary outcome
- postoperative morbidity and mortality
- pharmacokinetic parameters (systemic, intraperitoneal fluid concentrations of
oxaliplatin and docetaxel)
- cytoreductive completeness score
- patterns of tumour recurrence
- disease free and overall survival
Background summary
Patients with gastric cancer have a poor prognosis, this is partly because
these patients often develop peritoneal metastases. Peritoneal metastases in
gastric cancer give serious symptoms and a poor quality of life. Additionally,
patients with peritoneal metastases have a poor prognosis, usually between 3 to
6 months. Cytoreductive surgery combined with hyperthermic intraperitoneal
chemotherapy (HIPEC) is a relatively new treatment that is already used
successfully in patients with peritoneal metastases of colorectal cancer. At
HIPEC the inside of the abdomen is perfused with heated chemotherapy during the
operation, after the removal of cancerous growth. This happens to kill any
remaining invisible cancer cells. The HIPEC is an addition to the normal
operation of cancer. Although this treatment is applied to colon cancer, there
is little known about this treatment in Western gastric cancer patients. In
Asia, where stomach cancer is much more common, this treatment is already
extensively used successfully. The present study aims to develop a HIPEC
treatment in gastric cancer patients.
Study objective
Primary objective:
- to study the safety, tolerability and feasibility of gastrectomy combined
with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy
(HIPEC) after neoadjuvant systemic chemotherapy as primary treatment option for
advanced gastric cancer with tumour positive peritoneal cytology (C+) and/or
limited peritoneal carcinomatosis (P+).
Secondary objectives:
- to determine the maximum tolerated dose of intraperitoneal docetaxel in
combination with a fixed dose regimen of intraperitoneal oxaliplatin in gastric
cancer patients undergoing gastrectomy combined with cytoreductive surgery and
HIPEC after neoadjuvant systemic chemotherapy.
- to investigate the pharmacokinetics of intra-operative hyperthermic
intraperitoneal chemotherapy after gastrectomy and cytoreductive surgery in
patients with advanced gastric cancer and peritoneal dissemination.
- to identify genetic profiles predictive of tumour response in patients with
advanced gastric cancer and peritoneal dissemination undergoing gastrectomy
combined with cytoreductive surgery and HIPEC.
- to determine the two-year disease free and overall survival of advanced
gastric cancer patients with tumour positive peritoneal cytology (C+) and/or
limited peritoneal carcinomatosis (P+) treated with cytoreductive surgery and
HIPEC.
Study design
A multicenter, open label, dose-escalation phase I-II study aimed to evaluate
the safety, tolerability and feasibility of HIPEC with oxaliplatin and
docetaxel after neoadjuvant systemic chemotherapy in advanced gastric cancer
patients with tumour positive peritoneal cytology (C+) and/or limited
peritoneal carcinomatosis (P+). This will be accomplished by enrolling 20-30
patients meeting the inclusion criteria, using a 3+3 design. Safety will be
assessed by toxicity graded according to the NCI Common Toxicity Criteria
version 4.0.
Intervention
Diagnostic investigations
All patients with locally advanced (T3-T4, any N) gastric adenocarcinoma and no
evidence of distant metastasis with limited peritoneal dissemination or
positive peritoneal cytology treated with neoadjuvant chemotherapy will be
scheduled for surgery.
At laparotomy, the presence and extent of peritoneal tumour deposits will be
recorded. Any peritoneal fluid is sampled for cytology. When a potentially
radical resection of the primary tumour can be achieved, a total or partial
gastrectomy with a D2 lymph node dissection is performed. In patients with
limited peritoneal carcinomatosis, cytoreductive surgery (CRS) is done with the
objective to leave no macroscopic tumour behind.
HIPEC procedure
Intraperitoneal chemoperfusion is performed using an open HIPEC technique. At
an intraperitoneal temperature of 41-42 °C, 460 mg/m2 oxaliplatin is added to
the perfusate. After 30 minutes, the perfusion fluid is drained from the
abdomen. In successive patients a dose-escalation study will be performed with
0-50-75-100-125-150 mg/m2 docetaxel is administered in the peritoneal cavity
for 90 minutes.
Study burden and risks
The group of patients in which this treatment will be carried out have a poor
prognosis. This treatment offers these patients a potential life extension. The
burden of this study is the risk of complications of this treatment. Since it
is a partly experimental treatment in gastric cancer patient a strict patient
selection of patients has been chosen to only treat patients in which we expect
effect of the treatment. Furthermore, there are 7 additional blood tests are
carried out around the HIPEC treatment.
Plesmanlaan 121
Amsterdam 1066 CX
NL
Plesmanlaan 121
Amsterdam 1066 CX
NL
Listed location countries
Age
Inclusion criteria
• Biopsy proven adenocarcinoma of the stomach (including tumours at the oesophagogastric junction provided that the bulk of the tumour is located in the stomach for which the intended surgical treatment is a gastric resection and not a resection of the oesophagus and cardia)
• T3-T4 tumour based upon CT-scan and/or EUS results
• Tumour positive peritoneal cytology and/or peritoneal carcinomatosis limited to the upper abdominal cavity (above the transverse colon) and/or at the most at one location in the lower abdominal cavity (e.g., Douglas* pouch, ovarian metastasis, Sister Mary Joseph nodule) confirmed by diagnostic laparoscopy or laparotomy
• Treated with three courses of neoadjuvant chemotherapy consisting of a curative or palliative regimen, with the last course ending within 6 weeks prior to inclusion
• Age >= 18 years
• WHO performance status 0-1
• ASA classification I-III
• Adequate bone marrow, hepatic and renal function, i.e., minimal acceptable laboratory values at start of the study inclusion:
a. ANC >= 1.5 x 10^9 /L
b. Platelet count >= 100 x 10^9 /L
c. Serum bilirubin <= 1.5 x ULN, and ALAT and ASAT <= 2.5 x ULN
d. Creatinine clearance >= 50 ml/min (measured or calculated by Cockcroft-Gault formula).
• Negative pregnancy test (urine/serum) for female patients of childbearing potential
• Life expectancy >= 3 months allowing adequate follow up
• Able and willing to undergo blood sampling for pharmacokinetics
• Written informed consent
Exclusion criteria
• Distant metastases (e.g., liver, lung, para-aortic lymph nodes) or small bowel dissemination
• Signs of local irresectability
• Recurrent gastric cancer
• Metachronous peritoneal carcinomatosis
• Prior resection of the primary gastric tumour
• Pregnancy, breast feeding or active pregnancy ambition
• Unreliable contraceptive methods. Patients enrolled in this trial must agree to use a reliable contraceptive method throughout the study
• Uncontrolled infectious disease or known Human Immunodeficiency Virus HIV-1 or HIV-2 type
• A known history of hepatitis B or C with active viral replication
• Recent myocardial infarction (< 6 months) or unstable angina.
• Uncontrolled diabetes mellitus
• Any medical condition not yet specified above that is considered to possibly, probably or definitely interfere with study procedures, including adequate follow-up and compliance and/or would jeopardize safe treatment
• Known hypersensitivity for any of the applied chemotherapeutic agents and/or their solvents
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-000138-37-NL |
| CCMO | NL42799.031.13 |
| OMON | NL-OMON21196 |