Prophylactic HIPEC for Colorectal Cancers at High Risk of Developing Peritoneal Metastases

• ClinicalTrials.gov Identifier: NCT03422432
• Recruitment Status: Unknown
• First Posted: February 5, 2018
• Last Update Posted: February 5, 2018
• Sponsor: National Cancer Centre, Singapore
• Information provided by (Responsible Party): National Cancer Centre, Singapore

Study Description

Brief Summary:

The study investigators hypothesize that prophylactic HIPEC is feasible and well tolerated in patients with colorectal cancers with high-risk of developing peritoneal recurrence.

The aim of the pilot study is to test the feasibility of performing prophylactic HIPEC for colorectal cancer patients at high-risk of developing peritoneal recurrence in our institution, and determine the morbidity associated with such a procedure.

Patients with high-risk of developing peritoneal recurrence are defined as patients with

1. tumours involving the serosa and adjacent viscera (i.e. T4 cancers)
2. krukenburg tumours (i.e. ovarian metastases)
3. perforated tumours
4. positive peritoneal fluid cytology
5. minimal synchronous PC (nodules <1cm in the omentum and/or close to the primary tumour).

The study investigators plan to assess feasibility according to

1. The number of patients completing the treatment
2. Time to adjuvant systemic chemotherapy, to evaluate if there is delay to adjuvant treatment

Morbidity will be measured according to the Clavien-Dindo Classification, and graded according to low versus high grade morbidity.

If prophylactic HIPEC is shown to be feasible, with acceptable morbidity, the investigators aim to carry out a randomized controlled trial to determine the effectiveness of prophylactic HIPEC in preventing the development of peritoneal metastases in patients with colorectal cancer at high risk of peritoneal recurrence.

Condition or disease	Intervention/treatment	Phase
Colorectal Cancer; Peritoneal Metastases	Procedure: HIPEC	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 12 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Pilot Study: Prophylactic Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Colorectal Cancers at High Risk of Developing Peritoneal Metastases
• Actual Study Start Date: September 28, 2017
• Estimated Primary Completion Date: May 31, 2018
• Estimated Study Completion Date: May 31, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group 1; Patients are identified pre-operatively on radiological imaging. Prophylactic HIPEC will be delivered intra-operatively, immediately after the resection of the primary tumour, and only if the patient is deemed well enough to receive the HIPEC.	Procedure: HIPEC; All HIPEC will be with Mitomycin C and given at a dose of 10mg/body surface area.
Experimental: Group 2; Patients are identified post-operative based on histological findings. They will be counselled to receive prophylactic HIPEC only. If peritoneal nodules are found during surgery, these patients will be excluded from the study.	Procedure: HIPEC; All HIPEC will be with Mitomycin C and given at a dose of 10mg/body surface area.

Outcome Measures

Primary Outcome Measures :

1. The number of patients completing the treatment [ Time Frame: From start to end of study, approximately 1 year ]
2. Time to adjuvant systemic chemotherapy [ Time Frame: 3 months from date of surgery ]
   To evaluate if there is delay to adjuvant treatment

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Two groups of patients may be enrolled:

Group 1 patients are identified pre-operatively on radiological imaging, while Group 2 patients are identified post-operative based on histological findings.

All patients diagnosed with adenocarcinoma of the colon and rectum, and either one of the five following risk factors for peritoneal metastases will be considered for inclusion:

1. T4 tumours - in Group 1, this would consist of obvious clinical T4 stage based on preoperative imaging, and in Group 2, this would be on pathological confirmation of a T4 tumour.
2. Krukenburg tumours - Unilateral or bilateral ovarian masses seen on preoperative imaging
3. Perforated tumours - in Group 1, this would consist of patients presenting with perforation on preoperative imaging, and undergoing curative resection, and in Group 2, this would be on pathological or intra-operative confirmation of a perforated tumour.
4. Limited synchronous peritoneal metastases (peritoneal nodules <1cm in the omentum and/or close to the tumour). Patients with limited peritoneal disease in close proximity to the primary tumour, that may be removed enbloc with the primary resection can be included, but patients with more extensive peritoneal disease and those with extra-peritoneal metastases i.e. liver and/or lung metastases will be excluded from the study.
5. Positive cytology in Group 2 patients

Other inclusion criteria:

1. Patients must be between the ages of 21 and 75 years
2. Patients must be in a stable clinical condition to undergo simultaneous HIPEC after the primary curative colorectal resection
3. Patients must have an ECOG performance status 0 or 1
4. Patients must have normal organ and marrow function as defined below:

i. Absolute neutrophil count > 1.5 x 109/L ii. Platelets > 100 x 109/L iii. Haemoglobin > 9.0g/dl iv. Total bilirubin ≤1.5 x ULN v. AST(SGOT)/ALT(SGPT) < 3 X institutional ULN vi. Creatinine ≤1.5 x upper limit of normal (ULN) OR vii. Creatinine clearance ≥60 mL/min for patients with creatinine levels >1.5 x institutional UL e. Patients must have a normal coagulation profile f. Patients must give written informed consent

Exclusion Criteria:

1. Patients who are not fit to give consent for the procedure
2. Patients who are not fit to undergo surgery
3. Patients who are pregnant
4. Patients who have extensive synchronous peritoneal disease
5. Patients with extra-peritoneal metastases i.e. liver and/or lung metastases

Contacts and Locations

Contacts

Contact: Grace Tan, MD; +65 6436 8000; grace.tan.h.c@singhealth.com.sg

Locations

Singapore

National Cancer Centre Singapore; Recruiting

Singapore, Singapore, 169610

Contact: Grace Tan, MD +65 6436 8000 grace.tan.h.c@singhealth.com.sg

Principal Investigator: Grace Tan, MD

Sponsors and Collaborators

National Cancer Centre, Singapore

Investigators

• Principal Investigator: Grace Tan, MD; National Cancer Centre, Singapore

More Information

• Responsible Party: National Cancer Centre, Singapore
• ClinicalTrials.gov Identifier: NCT03422432
• Other Study ID Numbers: 2017/2402/B
• First Posted: February 5, 2018
• Last Update Posted: February 5, 2018
• Last Verified: January 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Colorectal Neoplasms; Neoplasm Metastasis; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes