Malignant Neoplasm of Large Intestine TNM Staging Primary Tumor (T) T4, Peritoneal Carcinomatosis
Conditions
Keywords
Peritoneal carcinomatosis, HIPEC, controlled clinical trial, colorectal cancer
Brief summary
Multicentric randomised trial. The goal of this clinical research study is to learn if hyperthermic intraperitoneal chemotherapy (HIPEC) will help to decrease the rate of peritoneal carcinomatosis(PC) in patients with high risk of developing PC of colorectal cancer. The safety of this treatment will also be studied.
Detailed description
Hyperthermic intraperitoneal chemotherapy(HIPEC) is a recently validated option for the treatment of peritoneal carcinomatosis from colorectal or ovarian origin. This therapeutic program demonstrated a significant improvement of overall survival of the disease. It is not yet known whether surgery followed by HIPEC is effective on decreasing the rate of peritoneal carcinomatosis(PC) in patients with high risk of developing PC of colorectal cancer.Patients with a high risk of developing colorectal Peritoneal Carcinomatosis (PC), defined by Colorectal Cancer With a Resected Minimal Synchronous PC or Ovarian Metastases, or identified T4 by intraoperative pathological diagnosis, or Tumour Rupture in the Abdominal Cavity. If patients with a high risk of developing PC identified by preoperative examination, they will be informed and will sign the consent. After complete resection of their tumor, they will be randomised to surveillance alone (control group) or HIPEC (experimental group). All patients will receive the current standard postoperative adjuvant treatment : 6 months of systemic chemotherapy (currently including FOLFOX4, mFOLFOX6, CapeOx or Capecitabine regimen which could be modified if the standard is modified). Then a work-up is done to find recurrence. If the recurrence occurs, the patient will be treated with the best known treatment.
Interventions
PROCEDURESurgery and Hyperthermic Intraperitoneal Chemotherapy with MMC
HIPEC with MMC: Mitomycin C (MMC) (30 mg/m2 of body surface area). Closed technique, as preferred. Duration: 60 minutes. Mean Intra-abdominal Temperature: 43°C.
Sponsors
Zhejiang University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients presenting with the following history: 1. Histologically-proven colorectal adenocarcinoma 2. Presenting at the time of resection of the primary with one of the following 5 criteria (criteria indicating a high risk of developing PC) : * Minimal PC, resected at the same time as the primary * Rupture of the primary tumour inside the peritoneal cavity, * Intraoperative rupture of the primary tumour during surgery * Histologically-proven T4 colorectal adenocarcinoma * Who have received standard systemic adjuvant chemotherapy (6 months of systemic chemotherapy) : 1. Chemotherapy with FOLFOX4, mFOLFOX6, CapeOx or Capecitabine(the current standard treatment; it can be modified in the future in the two groups, if the standard is modified) 2. Given on an intent-to-treat basis (it can be stopped prematurely for miscellaneous reasons) * Patients who do not present any sign of tumour recurrence at the end of these 6 months of chemotherapy * Patients with the following general characteristics: 1. Age between 18 and 75 years 2. Performance Status (ECOG) 0, 1 or 2, life expectancy \> 12 weeks 3. Adequate renal, and bone marrow function: a. Leukocytes \>/= 3,000/microL; b. Absolute neutrophil count \>/= 1,500/microL; c. Platelets \>/= 100,000/Ul; d. Serum creatinine \</= 1.5 mg/dL 4. Hepatic function: a. AST (SGOT)/ALT (SGPT) \</= 5 X institutional (Upper Limit of Normal) ULN 5. Operable patients 6. Completion of neoadjuvant systemic chemotherapy * Patients will be informed and a signed consent before initiating any procedure specific to the trial
Exclusion criteria
1. Cancers of non colorectal origin 2. Patients presenting with a detectable recurrent tumour 3. History of cancer (excepted cutaneous basal cell carcinoma or in situ carcinoma of the uterine cervix) with a recurrence during the 5 previous years 4. Known HIV, Hepatitis B or Hepatitis C positive 5. Pregnant women or likely to be pregnant 6. Persons under guardianship 7. Subjects deemed unable to comply with study and/or follow-up procedures. 8. Subjects with a known hypersensitivity to protocol systemic chemotherapy that was life-threatening, required hospitalization or prolongation of existing hospitalization, or resulted in persistent or significant disability or incapacity
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free survival | Three years from the date of randomization | DFS |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 3 year overall survival | 3 years | 3-OS |
| Peritoneal disease-free survival | 3 years | PDFS |
| 5 year overall survival | 5 years | 5-OS |
| morbidity | Baseline before any treatment,3 months post operation, 1 year post operation | Toxicity induced by HIPEC using the NCI CTC criteria; one month and six months morbidity. Subgroup analysis: pT4; pts. ≤ 40yrs. |
| QOL | Baseline before any treatment,3 months post operation, 1 year post operation | Duration of operation; return of bowel function; length of hospital stay; return to normal activity; six months and one year QOL, using the SF-36 v1.0; percentage of patients in both arms completing the scheduled postoperative chemotherapy; Subgroup analysis: pT4; pts. ≤ 40yrs. |
Countries
China
Outcome results
None listed