Colorectal Cancer, Peritoneal Metastases
Conditions
Brief summary
A dose titration study and a combined superiority registry-based open-label randomized control trial is planned to answer the trial objectives. The study will be registry-based to allow simpler and more comprehensive follow-up. Patients with colorectal cancer will be treated with cytoreductive surgery (CRS) together with either standard oxaliplatin HIPEC (the control for the efficacy study) or oxaliplatin/irinotecan HIPEC in combination with 5-FU 24-hour EPIC. The 5-FU will be administered postoperatively when the abdomen is completely sutured. The drug is divided equally into 2 injections of 200 ml each and injected through two abdominal drains that are clamped for 16 hours. For dose escalation, the titration groups (á 3 or 6 patients) are followed for 30 days postoperatively after which the Data Monitoring Committee (DMC) will determine whether or not to increase the 5-FU dose for the following group of patients. To study efficacy, randomization is performed intraoperatively. The patient is followed up postoperatively for a total of 3 years for the secondary endpoints which may be extended by the study committee to 5 years. Since the trial is registry based, the long-term follow-up does not require separate eCRF evaluations. These evaluations can be automatically retrieved from the registry - both recurrence data, quality of life, and morbidity data. Some specific eCRF evaluations will be integrated as a separate study part of the HIPEC registry, such as inclusion/exclusion criteria and adverse event reporting (including SUSAR reporting).
Detailed description
Not detailed description entered.
Interventions
DRUG5Fluorouracil
Injection of 250-850 mg/m2.
DRUGIrinotecan
Injection of 360 mg/m2
DRUGOxaliplatin
Injection of 460 mg/m2
Sponsors
Uppsala University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
1. Provision of written informed consent prior to any study specific procedures. 2. ECOG Performance Status Score 0,1 or 2 alternatively Karnofsky 60-100 3. Adequate kidney, liver, bone marrow function according to laboratory tests 4. For females of childbearing potential, a negative pregnancy test must be documented 5. ≥ 18 years old and ≤78 years old 6. Colorectal cancer with peritoneal metastases +/- liver metastases (maximum 3) 7. Concomitant resectable pulmonary metastases are allowed 8. All patients deemed eligible for CRS and HIPEC according to clinical routine management during a HIPEC multidisciplinary board at each respective hospital can be included.
Exclusion criteria
1. Previous severe toxicity/allergic reactions to systemic chemotherapy agents oxaliplatin or irinotecan or 5-fluorouracil 2. Unable to tolerate intensified HIPEC treatment due to comorbidity 3. Metastasis other than peritoneum or liver or lung 4. Complex liver-perenchymal sparing surgery or hemihepatectomy procedures are to be excluded. 5. Previous CRS or HIPEC 6. Pregnant or lactating (nursing) women 7. Active infections requiring antibiotics 8. Active liver disease with positive serology for active hepatitis B, C, or known HIV 9. Concurrent administration of any cancer therapy other than planned study treatment within 4 weeks prior to and up to 4 weeks after study treatment 10. Incomplete cytoreduction defined as completeness of cytoreduction score 2-3 11. Histopathology of other origin than colorectal cancer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recurrence-free survival | 24 months after treatment | To study the recurrence-free survival (RFS) of patients |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | 5 years after treatment | Survival is followed through the HIPEC registry. |
| Recurrence-free survival | 5 years after treatment | Survival is followed through the HIPEC registry. The RECIST criteria are used to determine recurrence and site of first recurrence |
| Postoperative complication rate | Within 30 days after treatment | Morbidity is registered in the HIPEC registry within 30 days of treatment administration. |
| Patient evaluations of quality of life | 3 years after treatment | EORTC QLQ questionnaire filled out at baseline, 12 and 36 months after surgery using the established QoL database. |
Countries
India, Sweden
Contacts
Primary ContactPeter Cashin, MD, PhD
Backup ContactLana Ghanipour, MD, PhD
Outcome results
None listed