To determine the safety, feasibility, and tolerability of adding PIPAC with oxaliplatin (92 mg/m2) to systemic chemotherapy in patients with isolated PM from CRC.
ID
Source
Brief title
Condition
- Malignant and unspecified neoplasms gastrointestinal NEC
- Metastases
- Gastrointestinal therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Major toxicity, defined as grade >2 according to the Common Terminology
Criteria for Adverse Events v4.0, and measured up to four weeks after the last
PIPAC procedure.
Secondary outcome
- Mild to moderate toxicity, defined as grade 1-2 according to the Common
Terminology Criteria for Adverse Events v4.0, and measured up to four weeks
after the last PIPAC procedure.
- The completed amount of cycles of bi-directional therapy with PIPAC and
systemic chemotherapy
- The completed amount of cycles of systemic chemotherapy; the amount dose
reductions, and reasons for dose reductions.
- Intra operative characteristics of PIPAC with oxaliplatin (e.g. laparoscopic
access rate, ascites volume, blood loss)
- Intra operative complications during PIPAC with oxaliplatin (e.g. bowel
perforation, bleeding)
- Length of hospital stay during bi-directional therapy with PIPAC and systemic
chemotherapy
- Readmission rate during bi-directional therapy with PIPAC and systemic
chemotherapy
- To determine nephrotoxicity, hepatotoxicity, and haematological toxicity of
bi-directional therapy with PIPAC and systemic chemotherapy
- To determine tumour markers (CEA) during bi-directional therapy with PIPAC
and systemic chemotherapy
- To determine macroscopic tumour respons during bi-directional therapy with
PIPAC and systemic chemotherapy
- To determine histopathological tumour resonse of tumour tissue and ascites
collected during second and third PIPAC
- To determine quality of life during bi-directional therapy with PIPAC and
systemic chemotherapy
- To determine intraperitoneal and systemic progression free survival after
bi-directional therapy with PIPAC and systemic chemotherapy
- To determine overall survival after bi-directional therapy with PIPAC and
systemic chemotherapy
- To collect blood and frozen tissue for translational research
- To determine the systemic pharmacokinetics of oxaliplatin after one cycle of
systemic chemotherapy and one PIPAC.
Background summary
The majority of patients with isolated peritoneal metastases (PM) from
colorectal cancer (CRC) do not qualify for curative intent treatment with
cytoreductive surgery and HIPEC (CRS/HIPEC), mostly due to extensive
intraperitoneal disease. In this particular group, the limited efficacy of
palliative systemic chemotherapy has encouraged the development of
intraperitoneal palliative therapies with a similar or increased efficacy and
low side effects.
Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) is such an innovative
therapy that carries a significant potential due to its minimally invasive
character, limited systemic toxicity, and encouraging preliminary efficacy and
quality of life outcomes. The addition of PIPAC to treatment with systemic
chemotherapy will hopefully result in long-term intraperitoneal disease control
without resulting in increased toxicity, thus preserving quality of life. The
PIPAC-I trial was the first Dutch study to investigate the safety, feasibility
and tolerability of PIPAC-monotherapy in patients with PM from CRC, showing
that PIPAC monotherapy is safe and well tolerated by patients. Yet there is no
experience in the Netherlands with adding the PIPAC-surgery to systemic
chemoteherapy. Therefore, this studie investigates the feasibility, safety,
tolerability and efficacy of bidirectional therapy consisting of PIPAC and
systemic chemotherapy.
Study objective
To determine the safety, feasibility, and tolerability of adding PIPAC with
oxaliplatin (92 mg/m2) to systemic chemotherapy in patients with isolated PM
from CRC.
Study design
This is a prospective, multi centre, single arm, phase II feasibility study.
Intervention
Besides regular treatment with palliative systemic chemotherapy, patients will
also receive three PIPAC-surgeries with oxaliplatin during a 9 week interval.
Each 0 week interval starts with 2-3 cycles of systemic chemotherapy and is
followed by a PIPAC surgery. After this, the next interval starts.
Study burden and risks
The most important risks associated with participation are toxicity related to
and inefficacy of PIPAC.
Patients that do not participate to the study, will only receive palliative
systemic chemotherapy, instead of bi-directional therapy consisting of systemic
chemotherapy and PIPAC. We expect that the addition of PIPAC will result in
only low systemic side effects, as shown in the PIPAC-I study and other
international studies (section 1.5 of the protocol).
Patients that participate in the trial will receive both the experimental
treatment (PIPAC) and the regular treatment (systemic chemotherapy). They
receive an extra treatment, possibly leading to increased intraperitoneal
disease control.
Therefore, the addition of PIPAC to regular systemic chemotherapy is considered
justified by the investigators, since the potential benefits (possible longer
term intraperitoneal disease control) overrule the potential harms (low risk of
toxicity)
Michelangelolaan 2
Eindhoven 5623EJ
NL
Michelangelolaan 2
Eindhoven 5623EJ
NL
Listed location countries
Age
Inclusion criteria
- 18 years or older
- Histologically confirmed PM from a colorectal (including appendiceal)
carcinoma that are not amenable for complete cytoreductive surgery, as
determined by laparotomy, laparoscopy or radiology.
- WHO performance score of 0-1
- Written informed consent
Exclusion criteria
- Radiological evidence of systemic metastatic disease (e.g. liver, lung);
- Symptomatic presentation (e.g. non-deviated obstructive symptoms);
- Histologically confirmed PM from a low grade appendiceal carcinoma
(Disseminated Peritoneal Adeno-Mucinosis / Low-grade Appendiceal Mucinous
Neoplasm);
- Inadequate organ functions, defined as an Hb of <5.0 mmol/L, an absolute
neutrophil count of <1.5 x 10^9/L, platelet count of <100 x 10^9/L, serum
creatinine of >1.5 x ULN, creatinine clearance (Cockroft formula) of <30
ml/min, and liver transaminases of >5 x ULN;
- Any contraindication for the planned chemotherapy (e.g. severe allergy,
pregnancy, uncompensated cardiac disease, coagulopathy, serious active
infections), as determined by the medical oncologist;
- Any contraindication for a laparoscopy, as determined by the surgeon and/or
anesthesiologist;
- Previous PIPAC-procedures;
- Previous treatment with palliative systemic chemotherapy (Note: this
criterium does not include patients that received systemic chemotherapy in a
(neo-)adjuvant setting. Patients treated with (neo-)adjuvant chemotherapy are
able to enrol in the study if this treatment was finished >6 months before
trial enrolment).
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 | EUCTR2019-002290-63-NL |
| CCMO | NL70298.100.19 |