This study has been transitioned to CTIS with ID 2024-516265-37-00 check the CTIS register for the current data. The primary goal of the study is to establish the maximum tolerated dose (MTD) of intraperitoneal administration of irinotecan, added to…
ID
Source
Brief title
Condition
- Peritoneal and retroperitoneal conditions
- Metastases
- Gastrointestinal therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The aim of this study is to establish the maximum tolerable dose and
recommended phase II dose of intraperitoneal irinotecan added to systemic
chemotherapy (capecitabine/oxaliplatin) in patients with peritoneal metastasis
of gastric origin.
Secondary outcome
Secondary 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 also collect and store ascites for
(future) translational research purposes and we will investigate the value of
the 68Ga-FAPI PET/CT for peritoneal response evaluation.
Background summary
Gastric cancer with peritoneal carcinomatosis has a poor prognosis, with little
treatment options available. The current treatment strategy consists of
palliative systemic chemotherapy. However, previous research suggests that
systemic chemotherapy is less effective against peritoneal carcinomatosis than
against metastases that spread hematogeneously. Several studies suggested that
in patients with peritoneal carcinomatosis, intraperitoneal chemotherapy may be
superior compared to intravenous chemotherapy. Intraperitoneal chemotherapy
could lead to higher concentrations of chemotherapy in the peritoneal cavity
for a longer period of time, resulting in an increased cumulative exposure to
the peritoneal metastases. A few Asian studies have shown promising results
with intraperitoneal chemotherapy in patients with peritoneal carcinomatosis of
gastric origin. However, intraperitoneal chemotherapy combined with systemic
chemotherapy has not been investigated in Western patients with peritoneal
carcinomatosis of gastric origin yet.
Study objective
This study has been transitioned to CTIS with ID 2024-516265-37-00 check the CTIS register for the current data.
The primary goal of the study is to establish the maximum tolerated dose (MTD)
of intraperitoneal administration of irinotecan, added to systemic
capecitabine/oxaliplatin (CAPOX) in patients with peritoneal carcinomatosis of
gastric origin. Secondary goals are to investigate the safety en feasibility of
this treatment, en to further investigate the pharmacokinetic profile of
intraperitoneal irinotecan. During this study, ascites will also be collected
systemically for further translational research and the value of FAPI PET/CT
will be evaluated for peritoneal response evaluation.
Study design
This study will be a phase I '3+3+3' dose-escalation study, performed in the
Erasmus MC, Rotterdam & Catharina Hospital, Eindhoven.
Intervention
Patients are first discussed in a multi-disciplinary tumor board for
eligibility for this study, that is macroscopic peritoneal metastases and no
other regular treatment options available. Patients will then be informed about
this study and after signing informed consent, a peritoneal access port will be
placed during a DLS in the abdomen of the patient. Through this port
intraperitoneal irinotecan will be administered (according to dose-escalation
schedule), in combination with systemic CAPOX. During the study, patients will
undergo 2 68Ga-FAPI-46 PET/CT scans; one prior to therapy initiation and one
after completion of the 6 cycles; these scans will be used to evaluate
peritoneal response.
Study burden and risks
The intervention will be an addition upon the regular systemic treatment.
Patients have to undergo extra outpatient visits for this study and extra
procedures for this trial, like placement of a peritoneal access port and
intravenous catheter. Risks are limited for these invasive procedures. The
extra intravenous catheter is necessary to establish the pharmacokinetic
profile of intraperitoneally administered irinotecan. The intraperitoneal
access port is necessary for the administration of intraperitoneal irinotecan
and for the collection of intraperitoneal fluid samples/ascites. Placement of
the intraperitoneal port will be performed according to standard procedures
during the planned diagnostic laparoscopy under general anesthesia. There is a
limited risk for complications, like infection. The administration of
intraperitoneal chemotherapy is a potential risk for treatment related
toxicities. This risk should be weighed against the potential survival benefit
of the treatment. Previous clinical studies showed that administration of
intraperitoneal irinotecan was feasible and overall well tolerated.
Additionally, patients will undergo FAPI PET/CT scans twice; the estimated
radiation dose from adding the FAPI PET is 0.82 mSv (compared to the 4.0 mSv
from the CT scan). We believe this slight increase is justified by the
potential for better assessment of peritoneal lesions through the FAPI PET/CT
scan.
Dr. Molewaterplein 40
Rotterdam 3015GD
NL
Dr. Molewaterplein 40
Rotterdam 3015GD
NL
Listed location countries
Age
Inclusion criteria
• Patients with a histologically confirmed diagnosis of HER2-negative gastric
cancer.
• A histologically confirmed diagnosis of macroscopic peritoneal carcinomatosis
(PCI >=1).
• Age >= 18 years old.
• Written informed consent according to the ICH-GCP and national/local
regulations.
• 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 or 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.
Exclusion criteria
• Medical or psychological impediment to probable compliance with the protocol.
• Serious concomitant disease or active infections.
• Distant metastasis other than peritoneal metastasis or metastatic lymph
nodes.
• No sufficient oral food intake.
• Polyneuropathy grade 2 or worse according to CTCAE version 5.0.
• 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 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 a 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.
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 |
|---|---|
| EU-CTR | CTIS2024-516265-37-00 |
| EudraCT | EUCTR2021-005907-11-NL |
| ClinicalTrials.gov | NCT05379790 |
| CCMO | NL79619.078.21 |