Bidirectional therapy, consisting of multiple cycles of systemic chemotherapy followed by ePIPAC-OX, could be more effective against colorectal peritoneal metastases as compared to monotherapy with either systemic chemotherapy or ePIPAC-OX, whilst…
ID
Source
Brief title
Health condition
Colorectal cancer, peritoneal metastases
Sponsors and support
Intervention
Outcome measures
Primary outcome
The number of patients with severe toxicity, measured up to 4 weeks after the last cycle of bidirectional therapy consisting of two/three cycles of systemic chemotherapy followed by a laparoscopic ePIPAC-OX procedure.
Secondary outcome
- The number of patients with moderate or mild toxicity, measured up to 4 weeks after the last cycle of bidirectional therapy consisting of two/three cycles of systemic chemotherapy followed by a laparoscopic ePIPAC-OX procedure; - The time period in which 20 patients are included in this study; - The technical difficulties during each laparoscopic ePIPAC-OX procedure; - The number of cycles of bidirectional therapy consisting of two/three cycles of systemic chemotherapy followed by a laparoscopic ePIPAC-OX procedures in each patient and reasons for discontinuation; - The number of cycles of systemic chemotherapy completed, the number of dose reductions, and reasons for discontinuation or dose reduction. - The possibility of laparoscopic access during each laparoscopic ePIPAC-OX procedure; - The amount of adhesions during each laparoscopic ePIPAC-OX procedure; - The volume of ascites during each laparoscopic ePIPAC-OX procedure; - The macroscopic tumour response of tumour tissue biopsied during second, third, and further laparoscopic ePIPAC-OX procedures; - The operating time of each laparoscopic ePIPAC-OX procedure; - The blood loss during each laparoscopic ePIPAC-OX procedure; - The occurrence of intraoperative complications (e.g. bowel perforation, bleeding) during each laparoscopic ePIPAC-OX procedure; - The hospital stay after each laparoscopic ePIPAC-OX procedure; - The number of patients with a readmission during repetitive cycles of bidirectional therapy consisting of two/three cycles of systemic chemotherapy followed by a laparoscopic ePIPAC-OX; - Renal, hepatic, haematological function at baseline, before each cycle of systemic chemotherapy, before each laparoscopic ePIPAC-OX, and 4 weeks after the final/third laparoscopic ePIPAC-OX; - Tumour markers at baseline, before each cycle of systemic chemotherapy, before each laparoscopic ePIPAC-OX, and 4 weeks after the final/third laparoscopic ePIPAC-OX. - The histopathological tumour response of tumour tissue and ascites biopsied during second and third laparoscopic ePIPAC-OX procedures; - Quality of life at baseline, 1 week before the first laparoscopic ePIPAC-OX, 1 and 4 weeks after each laparoscopic ePIPAC-OX; - Costs before first laparoscopic ePIPAC, 4 weeks after first laparoscopic ePIPAC-OX, 4 weeks after second laparoscopic ePIPAC-OX, 4 weeks after third laparoscopic ePIPAC-OX; - Systemic pharmacokinetics of oxaliplatin administered by PIPAC and by systemic therapy, allowing a direct comparison. Plasma and plasma ultrafiltrate will be collected in all patients after one PIPAC and after one cycle of systemic therapy with oxaliplatin. - The number of patients that are able to undergo secondary CRS & HIPEC; - The date of intraperitoneal tumour progression; - The date of radiologically confirmed systemic tumour progression; - The date of death due to any cause, and the cause of death;
Background summary
Rationale: Bidirectional therapy, consisting of multiple cycles of systemic chemotherapy followed by ePIPAC-OX, could be more effective against colorectal peritoneal metastases as compared to monotherapy with either systemic chemotherapy or ePIPAC-OX, whilst maintaining quality of life. However, there is no experience with bidirectional therapy in the Netherlands. Therefore, its safety and feasibility should be determined first. Study design: This is a prospective, multicentre, single arm, phase II study. Study population: Twenty adults (WHO 0-1) with histologically confirmed asymptomatic isolated irresectable PM from a colorectal or appendiceal carcinoma, without contraindications for laparoscopy or the planned chemotherapy, and without previous PIPAC-procedures. Intervention: Repetitive cycles of palliative systemic chemotherapy followed by laparoscopic ePIPAC-OX. Primary endpoint: The number of patients with major toxicity, defined as a grade ≥3 according to the Common Terminology Criteria for Adverse Events v5.0, and measured up to four weeks after the last cycle of laparoscopic ePIPAC-OX and systemic chemotherapy. Nature and extent of the burden and risks and benefits associated with participation: Treatment with repetitive ePIPAC-OX is associated with low rates of systemic toxicity. Therefore, we hypothesise to observe comparable rates of toxicity in patients treated with bidirectional therapy as in patients treated with systemic chemotherapy alone. Addition of repetitive ePIPAC-OX could induce greater control of intraperitoneal disease.
Study objective
Bidirectional therapy, consisting of multiple cycles of systemic chemotherapy followed by ePIPAC-OX, could be more effective against colorectal peritoneal metastases as compared to monotherapy with either systemic chemotherapy or ePIPAC-OX, whilst maintaining quality of life. However, there is no experience with bidirectional therapy in the Netherlands. Therefore, its safety and feasibility should be determined first.
Study design
See sections 'primary outcomes' and 'secondary outcomes' above
Intervention
Bidirectional therapy Patients are treated with three rounds of bidirectional therapy. Each round of bidirectional therapy consists of 2 cycles of systemic chemotherapy with CAPOX-bevacizumab OR 3 cycles of systemic chemotherapy with FOLFOX-bevacizumab / FOLFIRI-bevacizumab / FOLFOXIRI-bevacizumab. After 2 or 3 cycles of systemic chemotherapy, patients receive 1 electrostatic PIPAC with oxaliplatin (92 mg/m2) with a simultaneous intravenous bolus of 5-fluorouracil (400 mg/m2) and leucovorin (20 mg/m2). After three rounds of bidirectional therapy, patients have received a maximum of three PIPACs. PIPAC with oxaliplatin During PIPAC, oxaliplatin (92 mg/m2) is aerosolized during a laparoscopic surgery with an average pressure of 12 mm Hg. After complete injection (5 minutes), electrostatic precipitation is applied by using CE-certified Ultravision® technology. After electrostatic precipitation, the therapeutic capnoperitoneum is maintained for another 25 minutes.
Robin Lurvink
00402396354
robin.lurvink@catharinaziekenhuis.nl
Robin Lurvink
00402396354
robin.lurvink@catharinaziekenhuis.nl
Inclusion criteria
- 18 years or older; - Histologically confirmed PM from a colorectal (including appendix) carcinoma that are not amenable for complete cytoreductive surgery, determined by radiology, laparotomy or laparoscopy; - WHO performance score of 0-1 and life expectancy >3 months; - 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. (neo-)adjuvant systemic chemotherapy has to be administered >6 months before trial inclusion to be eligible for trial participation).
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL8303 |
| CCMO | NL70298.100.19 |
| EudraCT | 2019-002290-63 |
| OMON | NL-OMON50015 |