Chemo-immunotherapy before and after surgery for peritoneal metastases of large bowel cancer
- Conditions
- Current condition as of 11/01/2019:Isolated resectable colorectal peritoneal metastasesPrevious condition:Colorectal cancer with isolated peritoneal metastasesCancer
- Registration Number
- ISRCTN15977568
- Lead Sponsor
- Catharina Hospital (Netherlands)
- Brief Summary
2019 Protocol article in https://www.ncbi.nlm.nih.gov/pubmed/31023318 protocol (added 29/04/2019)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 358
Current inclusion criteria as of 11/01/2019:
1. A World Health Organisation (WHO) performance status of =1
2. Histological or cytological proof of peritoneal metastases of a non-appendiceal colorectal adenocarcinoma with =50% of the tumour cells being signet ring cells
3. Resectable disease determined by abdominal computed tomography (CT) and a diagnostic laparoscopy/laparotomy
4. No evidence of systemic colorectal metastases within three months prior to enrolment
5. No systemic therapy for colorectal cancer within six months prior to enrolment
6. No contraindications for CRS-HIPEC
7. No previous CRS-HIPEC
8. No concurrent malignancies that interfere with the planned study treatment or the prognosis of resected colorectal peritoneal metastases.
Importantly, enrolment is allowed for patients with radiologically non-measurable disease. The diagnostic laparoscopy/laparotomy may be performed in a referring centre, provided that the peritoneal cancer index (PCI) is appropriately scored and documented before enrolment.
Inclusion criteria as of 04/05/2017:
1. PCI score =20 and CC-0 or CC-1 achievable, determined by adequate preoperative work-up
2. Histological confirmation of non-appendiceal colorectal cancer with non-signet histology in peritoneal deposits or ascites
3. 18 years or older
4. WHO performance score 0-1
5. Adequate clinical condition to undergo cytoreductive surgery with HIPEC and/or neoadjuvant combination chemotherapy with bevacizumab within 4 weeks after randomisation
6. Adequate organ functions: normal bone marrow function (Hb =6.0 mmol/L, absolute neutrophil count =1.5 x 109/L, platelet count =100 x 109/L), renal function (serum creatinine =1.5 x ULN and creatinine clearance [Cockroft formula] =30 ml/min), determined <3 months prior to randomisation;
7. No known bleeding diathesis or coagulopathy
8. Written informed consent
9. Able and willing to adhere to follow-up
Previous inclusion criteria:
1. Peritoneal Cancer Index (PCI) score =20, determined by diagnostic staging laparoscopy
2. Achievability of complete cytoreduction, determined by diagnostic staging laparoscopy
3. Pathological confirmation of non-signet adenocarcinoma in peritoneal deposits or ascites
4. 18 years or older
5. WHO performance score 0-1
6. Adequate clinical condition to undergo CRS + HIPEC and neoadjuvant systemic therapy within 4 and 3 weeks after staging laparoscopy, respectively
7. Neutrophil count of at least 3.000/mm3, platelet count of at least 100,000/mm3 (<3 months before inclusion)
8. No bleeding diathesis or coagulopathy
9. Normal creatinine or creatinine clearance, determined by the MDRD-formula, of at least 50 ml/min (<3 months before inclusion)
10. Written informed consent
11. Expected adequacy of follow-up
Current exclusion criteria as of 11/01/2019:
1. Inadequate bone marrow, renal, or liver functions (e.g. haemoglobin <6.0 mmol/L, neutrophils <1.5 x 109/L, platelets <100 x 109/L, serum creatinine >1.5 x ULN, creatinine clearance <30 ml/min, bilirubin >2 x ULN, serum liver transaminases >5 x ULN);
2. Previous intolerance of fluoropyrimidines or both oxaliplatin and irinotecan;
3. Dehydropyrimidine dehydrogenase deficiency;
4. Serious active infections;
5. Severe diarrhoea;
6. Stomatitis or ulceration in the mouth or gastrointestinal tract;
7. Recent major cardiovascular events;
8. Unstable or uncompensated respiratory or cardiac disease;
9. Bleeding diathesis or coagulopathy;
10. Pregnancy or lactation.
Exclusion criteria as of 04/05/2017:
1. Signet ring cell histology (>50% of the cells have signet ring cell histology) of the primary tumour
2. Systemic metastases (i.e. liver, lung)
3. Known pregnancy or lactation, wish for pregnancy, and not willing to use contraceptives
4. Known unstable or uncompensated respiratory or cardiac disease
5. Serious active infections
6. Adjuvant chemotherapy after primary resection of colorectal cancer within 6 months prior to randomisation;
7. Any condition not allowing the safe administration of the planned systemic treatment (bevacizumab, 5-fluorouracil, leucovorin, capecitabine, oxaliplatin, irinotecan)
8. Stomatitis, ulceration in the mouth or gastrointestinal tract
9. Severe diarrhoea
10. Known pernicious anaemia or other anaemias due to vitamin B12 deficiency
11. Known previous peripheral sensory neuropathy with functional impairment after previous use of oxaliplatin
12. Impaired liver function (serum bilirubin =2 x ULN, serum transaminases =5 x ULN), assessment only if indicated
Previous exclusion criteria from 02/09/2016 to 04/05/2017:
1. Signet ring cell histology (>50% of the cells have signet ring cell histology) of the primary tumour
2. Systemic metastases (i.e. liver, lung)
3. Known pregnancy or lactation
4. Known unstable or uncompensated respiratory or cardiac disease
5. Serious active infections
6. Adjuvant chemotherapy after primary resection of colorectal cancer used within 6 months prior to randomisation
7. Any condition not allowing the safe administration of the planned systemic treatment (bevacizumab, 5-fluorouracil, leucovorin, capecitabine, oxaliplatin, irinotecan)
8. Stomatitis, ulceration in the mouth or gastrointestinal tract
9. Severe diarrhoea
10. Known pernicious anaemia or other anaemias due to vitamin B12 deficiency
11. Known previous peripheral sensory neuropathy with functional impairment after previous use of oxaliplatin.
12. Impaired liver function (serum bilirubin =2 x ULN, serum transaminases =5 x ULN), assessment only if indicated
13. Known dihydropyrimidine dehydrogenase deficiency, determined by dihydropyrimidine dehydrogenase genotyping
Original exclusion criteria:
1. Signet ring cell histology (>50% of the cells have signet ring cell histology) of the primary tumour
2. Pregnant or lactating women
3. Unstable or uncompensated respiratory or cardiac disease
4. Serious active infections
5. Other concurrent chemotherapy used within 6 months prior to inclusion
6. Any condition not allowing the safe administration of the planned systemic treatment (bevacizumab, fluorouracil, folinic acid, capecitabine or oxaliplatin/irinotecan)
7. Stomatitis, ulceration in the mouth or gastrointestinal tract
8. Severe diarrhoea
9. Severe hepatic and/or renal dysfunction
10. Plasma
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method