Clinical trial NCT01226394: Trial Comparing Simple Follow-up to Exploratory Laparotomy Plus "in Principle" (Hyperthermic Intraperitoneal Chemotherapy) HIPEC in Colorectal Patients
Official title: Multicentric Phase III Trial Comparing Simple Follow-up to Exploratory Laparotomy Plus "in Principle" HIPEC (Hyperthermic Intraperitoneal Chemotherapy) in Colorectal Patients Initially Treated With Surgery and Adjuvant Chemotherapy Who Have a High Risk of Developing Colorectal Peritoneal Carcinomatosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Colorectal Cancer With a Resected Minimal Synchronous PC
Ovarian Metastases
Tumour Rupture in the Abdominal Cavity
Keywords: peritoneal carcinomatosis
HIPEC
controlled clinical trial
Lead sponsor: Gustave Roussy, Cancer Campus, Grand Paris
Sponsor class: OTHER
First posted: 2010-10-22
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Multicentric randomised trial. Patients with a high risk of developing colorectal Peritoneal Carcinomatosis (PC) after resection of their primary will be informed, will sign the consent and will be pre-registered. All patients will receive the current standard adjuvant treatment : 6 months of systemic chemotherapy (currently the Folfox-4 regimen which could be modified if the standard is modified). Then a work-up is done to exclude recurrence. The likelihood of a recurrence is low but if this occurs, the patient will not be randomised and will be treated with the best known treatment. If the work-up is negative, patients will be randomised to surveillance alone (control group) or exploratory laparotomy + HIPEC (experimental group).


Eligibility criteria: Inclusion Criteria:

A) 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 4 criteria (criteria indicating a high risk of developing PC) :

   * Minimal PC, resected at the same time as the primary
   * Ovarian metastases
   * Rupture of the primary tumour inside the peritoneal cavity,
   * Iatrogenic rupture of the primary tumour during surgery

B) Who have received standard systemic adjuvant chemotherapy (6 months of systemic chemotherapy) :

* Chemotherapy with the Folfox 4 regimen (the current standard treatment ; it can be modified in the future in the two groups, if the standard is modified...).
* Given on an intent-to-treat basis (it can be stopped prematurely for miscellaneous reasons...);

C) Patients who do not present any sign of tumour recurrence at the end of these 6 months of chemotherapy.

D) Patients with the following general characteristics:

1. Age between 18 and 70 years,
2. Performance Status WHO \< 2, life expectancy \> 12 weeks,
3. Haematological parameters : Polynuclear neutrophils ³ 1.5x109/L, platelets ³ 100x109/L,
4. Liver function : Total Bilirubin £ 1.5 x ULN, AST (SGOT) et ALT (SGPT) £ 3 x ULN, alkaline phosphatases £ 3 x ULN,
5. Renal function : Plasma creatinine £ 1,25 x ULN,
6. Operable patients,
7. Grade £ 2 peripheral neuropathy (CTC AE v3.0 annex 7)
8. Patients entitled to French National Health Insurance coverage.

E)Patients will be informed and a signed consent form will be obtained before initiating any procedure specific to the trial.

Exclusion Criteria:

1. Cancers of non colorectal origin, particularly, appendiceal cancers are excluded
2. Patients presenting with a detectable recurrent tumour
3. Grade ≥ 3 Peripheral neuropathy
4. History of cancer (excepted cutaneous basocellullar cancer or in situ carcinoma of the uterine cervix) with a recurrence during the 5 previous years
5. Patients already included in another trial concerning first-line treatment 6) Pregnant women or likely to be pregnant

7) Persons under guardianship 8) Follow-up impossible for geographic, social or psychological reasons

Primary outcomes:
measure: To increase the 3-year disease-free survival
timeFrame: 3 years
Secondary outcomes:
measure: 3 year overall survival
timeFrame: 3 years
measure: Peritoneal disease-free survival
timeFrame: 3 years
measure: 5 year overall survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Gustave Roussy, Cancer Campus, Grand Paris
name: Diane GOERE, MD
role: STUDY_CHAIR
References:
citation: Goere D, Glehen O, Quenet F, Guilloit JM, Bereder JM, Lorimier G, Thibaudeau E, Ghouti L, Pinto A, Tuech JJ, Kianmanesh R, Carretier M, Marchal F, Arvieux C, Brigand C, Meeus P, Rat P, Durand-Fontanier S, Mariani P, Lakkis Z, Loi V, Pirro N, Sabbagh C, Texier M, Elias D; BIG-RENAPE group. Second-look surgery plus hyperthermic intraperitoneal chemotherapy versus surveillance in patients at high risk of developing colorectal peritoneal metastases (PROPHYLOCHIP-PRODIGE 15): a randomised, phase 3 study. Lancet Oncol. 2020 Sep;21(9):1147-1154. doi: 10.1016/S1470-2045(20)30322-3. Epub 2020 Jul 24.