Surgery With HIPEC in Treating Patients With a High Risk of Developing Colorectal Peritoneal Carcinomatosis

Peritoneal Carcinomatosis Clinical Trial

Official title:

Randomized Multicentric Phase III Trial Comparing Simple Surgery to Surgery Plus HIPEC (Hyperthermic Intraperitoneal Chemotherapy) With MMC in Colorectal Patients Who Have a High Risk of Developing Colorectal Peritoneal Carcinomatosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02179489
• Other study ID #: CRCCZ-C01
• Status: Completed
• Phase: N/A
• Start date: November 1, 2014
• Est. completion date: November 30, 2021

Study information

• Verified date: June 2022
• Source: Zhejiang University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 271
• Est. completion date: November 30, 2021
• Est. primary completion date: November 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Colorectal Neoplasms
• Malignant Neoplasm of Large Intestine TNM Staging Primary Tumor (T) T4
• Neoplasms
• Peritoneal Carcinomatosis
• Peritoneal Neoplasms

Intervention

Procedure:
• Surgery 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.

Locations

Country	Name	City	State
China	Union Hospital Fujian Medical University	Fuzhou	Fujian
China	Second Affiliated Hospitalof Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Sir Run Run Shaw Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	The First Affiliated Hospital of College of Medicine Zhejiang University	Hangzhou	Zhejiang
China	Jinhua People's Hospital	Jinhua	Zhejiang
China	Zhongshan Hospital Fudan University	Shanghai	Shanghai
China	People's Hospital of Shaoxing	Shaoxing	Zhejiang
China	Liaoning Cancer Hospital	Shenyang	Liaoning
China	Yuyao People's Hospital	Yuyao	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Zhejiang University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free survival	DFS	Three years from the date of randomization
Secondary	3 year overall survival	3-OS	3 years
Secondary	Peritoneal disease-free survival	PDFS	3 years
Secondary	5 year overall survival	5-OS	5 years
Secondary	morbidity	Toxicity induced by HIPEC using the NCI CTC criteria; one month and six months morbidity.; Subgroup analysis: pT4; pts. = 40yrs.	Baseline before any treatment,3 months post operation, 1 year post operation
Secondary	QOL	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.	Baseline before any treatment,3 months post operation, 1 year post operation