Main objective of this project is to establish the maximum tolerable dose (MTD) and recommended phase II dose of intraperitoneal irinotecan in patients with PC of colorectal origin, added to standard of care systemic chemotherapy. Other endpoints…
ID
Source
Brief title
Condition
- Peritoneal and retroperitoneal conditions
- Metastases
- Gastrointestinal therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary outcome is the MTD and recommended phase II dose of intraperitoneal
irinotecan
Secondary outcome
Secundary outcomes are the safety and feasibility of this treatment and to
establish the pharmacokinetic profile of intraperitoneal administered
irinotecan
Background summary
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy
(HIPEC) has become standard of care for patients with peritoneal carcinomatosis
(PC) of colorectal origin with a low/moderate abdominal disease load. In case
of a Peritoneal Carcinomatosis Index (PCI) >20, CRS-HIPEC procedure is not
considered to be beneficial. Patients who have undergone an open-close
procedure are offered palliative/life prolonging systemic chemotherapy.
Previous research shows that systemic chemotherapy is less effective against
peritoneal carcinomatosis than it is against hematogeneous spread of colorectal
cancer. Several studies suggested that in patients with PC, intraperitoneal
chemotherapy may be superior to intravenous chemotherapy. The addition of
intraperitoneal to systemic chemotherapy in patients with PC of ovarian and
gastric origin showed promising results. As of yet, there are no studies
investigating intraperitoneal chemotherapy for PC of colorectal origin in this
specific patient population
Study objective
Main objective of this project is to establish the maximum tolerable dose (MTD)
and recommended phase II dose of intraperitoneal irinotecan in patients with PC
of colorectal origin, added to standard of care systemic chemotherapy. Other
endpoints are to explore the safety and feasibility of this treatment and to
establish the pharmacokinetic profile of intraperitoneal administered
irinotecan. During this study we will systematically collect and store ascites
for translational research purposes.
Study design
This study is a classic phase I *3+3* dose-escalation study, which will be
conducted in the Erasmus MC, Rotterdam and Catharina Hospital, Eindhoven.
Intervention
According to standard work-up for CRS-HIPEC procedure, patients will undergo a
planned diagnostic laparoscopy to score the extend of peritoneal carcinomatosis
(PCI). In case of a PCI >20, a peritoneal access port will be placed. Through
this port we will administer intraperitoneal irinotecan (according to
dose-escalation schedule), in combination with standard of care chemotherapy:
systemic fluorouracil and oxaliplatin (FOLFOX) + bevacizumab.
Study burden and risks
The intervention comes in addition to the standard of care. In participating
patients a peritoneal access port will be surgically implanted. Patients will
receive intraperitoneal chemotherapy through this port. This happens at the
same time as the treatment with systemic chemotherapy. According to Dutch
guidelines, patients will receive chemotherapy every 2 weeks, for a maximum of
12 cycles. Participating patients will have additional outpatient hospital
visits and have to undergo some extra invasive procedures, like venapunction of
intravenous catheter. The risks of these procedures are limited.
The addition of intraperitoneral chemotherapy to systemic chemotherapy forms an
increased risk for toxicity. That is why this is subject of our study. Previous
clinical studies in patients with ovarian and gastic cancer showed that the
administration of intraperitoneal chemotherapy in combination to systemic
chemotherapy is safe and feasible.
Dr. Molenwaterplein 40
Rotterdam 3015 GD
NL
Dr. Molenwaterplein 40
Rotterdam 3015 GD
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all
of the following criteria:* Patients with a histologically confirmed diagnosis
of colorectal cancer
* Radiologically or clinically confirmed diagnosis of peritoneal carcinomatosis
* Age * 18 years old
* Written informed consent according to the ICH-GCP and national/local
regulations
* Unknown PCI for which a DLS is planned in the work-up for a HIPEC-procedure
OR known PCI >20 evaluated by laparoscopy or laparotomy before inclusion in
this trial
* Patients must be ambulatory, WHO performance status 0 or 1 (Appendix A
protocol)
* Life expectancy of at least 3 months
* Ability to return to the Erasmus MC/Catharina Hospital for adequate follow-up
as required by this protocol
* Patients must have normal organ function and adequate bone marrow reserve as
assessed by the following laboratory requirements:
o absolute neutrophil count >1.5 * 10^9/l
o platelet count >100*10^9/l
o Hb>6.0mmol/l
o Bilirubin < 1.5x upper limit of normal (ULN)
o Serum AST and ALT < 2.5 x ULN
o GFR>45 and Creatinine clearance <2 x ULN
therap
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:* Extra-abdominal disease/metastatic disease
established by preoperative CT-scan of thorax-abdomen and/or PET-scan. Imaging
not older than 6 weeks at time of surgery
* Prior cytoreductive surgery
* Prior treatment with systemic chemotherapy for (metastatic) colorectal cancer
within the last 6 months
* Medical or psychological impediment to probable compliance with the protocol
* Serious concomitant disease or active infections
* History of auto-immune disease or organ allografts, or with active or chronic
infection, including HIV and viral hepatitis
* Serious intercurrent chronic or acute illness such as pulmonary (COPD or
asthma) or cardiac (NYHA class III or IV) or hepatic disease or other illness
considered by the study coordinator to constitute an unwarranted high risk for
participation in this study
* Homozygous UGT1A1*28 genotype
* Homozygous or (compound) heterozygous DPYD genotype (tested for *2A, *13,
2846A>T, and 1236G>A)
* Current use of strong CYP3A4-inhibitors or inducers. If patients use this
CYP3A4-modulating medication, it is allowed to stop it within 14 days of start
of treatment
* Pregnant or lactating women
* Concomitant participation in another competing clinical study
* Absence of assurance of compliance with the protocol
* An organic brain syndrome or other significant psychiatric abnormality which
would comprise the ability to give informed consent, and preclude participation
in the full protocol and follow-up
therap
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
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR 2018-000479-3-NL |
| CCMO | NL63809.078.18 |