None listed
Conditions
Brief summary
This study is investigating a novel personalised medicine approach to the use of Hyperthemic Intraperitoneal Chemotherapy (HIPEC) at the time of Cytoreductive Surgery (CRS) for Colorectal Periotneal Metastases (CPM). Who is it for? You may be eligible for this study if you are a patient aged 18-85 years old with synchronous or metachronous peritoneal metastases of colorectal adenocarcinoma origin, who has been deemed suitable for consideration of Cytoreductive surgery and HIPEC (i.e. radiologically has potentially resectable disease either upfront of after neoadjuvant chemotherapy). Study details Participants enrolled in this study will receive a novel personalised medicine approach by preclinically determining an individual patient's tumour response to chemotherapy prior to its administration intraperitoneally (HIPEC) at the time of their routine cytoreductive surgery. Delivery of CRS and personalised HIPEC will be compared to a historical cohort of patients who received non-personalised treatment to determine improvement in peritoneal disease free survival. Data on overall survival, cancer-specific survival, adverse events, surgical complications and patient-reported outcomes will also be collected. It is hoped that findings from this study will help address the current knowledge gap regarding the benefit of HIPEC+CRS, and therefore inform national guidelines for CPM management with international impact.
Interventions
Delivery of personalised Hyperthermic intraperitoneal chemotherapy (HIPEC) at the time of Cytoreductive Surgery, where the intraperitoenal drug choic is determined by a preclinical in-vitro drug assay performed on patient-derived tumour models in the laboratory. A tumour biopsy will be obtained at the time of routine staging laparoscopy and used to develop an in-vitro 3D tumour model in the laboratory to be tested against the three on-label Colorectal HIPEC drugs (Mitomycin-C, Oxaliplatin, Irino
Delivery of personalised Hyperthermic intraperitoneal chemotherapy (HIPEC) at the time of Cytoreductive Surgery, where the intraperitoenal drug choic is determined by a preclinical in-vitro drug assay performed on patient-derived tumour models in the laboratory. A tumour biopsy will be obtained at the time of routine staging laparoscopy and used to develop an in-vitro 3D tumour model in the laboratory to be tested against the three on-label Colorectal HIPEC drugs (Mitomycin-C, Oxaliplatin, Irinotecan). The intervention (personalised HIPEC) will be performed at the time of routine cytoreductive surgery across all Australian Colorectal Peritoneal Malignancy Units. Personalised HIPEC will be delivered during the cytoreductive surgery after a complete cytoreduction has been performed, where no macroscopic peritoneal disease exists in the abdominal cavity. HIPEC will be delivered via either a closed technique (with closure of the abdomen and delivery via abdominal drains) or open coliseum technique. The intraperitoneal chemotherapy will be heated to 40-42 degrees Celsius. The drug choice for HIPEC delivery will be determined by the results of the preclinical drug assay and will be a choice of one of the following: 1) 60 minutes Mitomycin C 15mg/m2 2) 60 minutes Oxaliplatin 350mg/m2 3) 60 minutes Irinotecan 100mg/m2 Cytoreductive surgery will be performed with an open approach via a midline laparotomy, with an approximate average duration of 5 hours. All cytoreductions will be performed by surgeons with specialist experience in peritoneal malignancy and its management and only at specialist Peritoneal Malignancy units. Adherence to quality of cytoreduction and its completeness will be monitored using intra-operative photography to document complete cytoreduction as well as review of the procedural records. The response of an individual organoid will be compared to the median response of the existing colorectal organoid library and a drug-sensitivity assay report will be generated to compare individual patient organoid response and determine individual sensitivity. Prior to release of the drug sensitivity report to the site investigator, results will be reviewed by a Personalised Medicine Tumour Board, consisting of a senior laboratory member, scientist, analyst and treating clinical team. The role of this board is to review assay results and govern their application into clinical practice.
Sponsors
Peter MacCallum Cancer Centre
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Patient has provided written informed consent using the PREDICTORG Patient Information and Consent Form (PICF) 2. Patient aged 18-85 years old at the time of signing consent. 3. Eastern Co-operative Oncology group (ECOG) performance status of 0-1 4. Patient deemed suitable for consideration of Cytoreductive surgery and HIPEC (i.e. radiologically has potentially resectable disease either upfront of after neoadjuvant chemotherapy) NOTE: Any co-morbidities are allowed provided the patient is deemed operable. 5. Synchronous or metachronous peritoneal metastases NOTE: Any previous radiotherapy or chemotherapy will be allowed, and no washout period is mandatory). 6. Histological confirmation of disease of colorectal adenocarcinoma origin. NOTE: in the setting of patients waiting for a histological diagnosis at the time of laparoscopy and biopsy, a strong suspicion of Colorectal Peritoneal Metastases based on imaging or tumour marker status is required for recruitment. 7. Life expectancy of at least 12 weeks.
Exclusion criteria
1. Extraperitoneal disease not amenable to curative treatment 2. Histology inconsistent with Colorectal Peritoneal Metastases (e.g. appendiceal cancer) 3. Previous Cytoreductive surgery and/or Hyperthemic Intraperitoneal Chemotherapy. 4. Patient already included in another first-line therapeutic trial for the disease studied. 5. Patients unable to undergo medical monitoring during the study due to geographical, social or psychological motives.
Outcome results
None listed