Clinical trial NCT03028155: Concentration- Versus Body Surface Area-based HIPEC in Colorectal Peritoneal Carcinomatosis' Treatment
Official title: Concentration-based Versus Body Surface Area-based Peroperative Intraperitoneal Chemotherapy (HIPEC) After Optimal Cytoreductive Surgery in Colorectal Peritoneal Carcinomatosis' Treatment - Randomized Non-blinded Phase III Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Colorectal Peritoneal Carcinomatosis
Lead sponsor: Hasselt University
Sponsor class: OTHER
Collaborators: name: Ziekenhuis Oost-Limburg
First posted: 2017-01-23
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Colorectal Cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death worldwide. CRC frequently gives rise to transcoelomic spread of tumor cells in the peritoneal cavity, which ultimately leads to Peritoneal Carcinomatosis (PC). A new loco-regional treatment modality combines Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Peroperative Chemotherapy (HIPEC). The current HIPEC dosing regimens for the treatment of colorectal PC can be divided into body surface area (BSA)-based protocols and concentration-based protocols. Most groups currently use a drug dose based on calculated BSA (mg/m2) in analogy to systemic chemotherapy regimens. These regimens take BSA as a measure for the effective contact area, represented as the peritoneal surface in the formula for dose intensification. However, an imperfect correlation exists between actual peritoneal surface area and calculated BSA. Sex differences, but also altered pathophysiological characteristics or frequent complications in patients (ascites) are responsible for differences in peritoneal surface areas, which in turn affect absorption characteristics. This takes us away from the initial homogenous drug concentration desired, increasing the variability in the systemic and tumor exposure to the drug. Pharmacokinetic changes induced by the volume of chemotherapy solution with constant drug dose, administered intraperitoneally, have already been reported. This resulted in less precise predictions of the toxicity associated with the treatment. By contrast, some groups use a totally different dosimetry regimen based on concentration. From a pharmacologic point of view, the big advantage of a concentration-based system is that the residual tumor nodules after CRS are exposed to a constant diffusional force and, thus, cytotoxicity. Unfortunately the prize to be paid for a better prediction of the efficacy of the IP chemotherapy is a high unpredictability of the levels of plasmatic cancer chemotherapy and, thus, toxicity. This randomised non-blinded phase III clinical trial will be the first trial to pharmacologically evaluate the two dosing regimens, BSA-based and concentration-based, both applied as standard of care in current practice.


Eligibility criteria: Inclusion Criteria:

* Males and females with histologically proven synchronous or metachronous peritoneal metastases from colorectal origin
* Karnofsky index \> 70%
* Age \>18 years
* Fit for major surgery
* Mentally capable of understanding the proposed treatment and the provided informed consent
* Estimated life expectancy of \> 6 months
* Absence of other malignant disease
* Serum creatinine \< or = 1.5 mg/dL or calculated glomerular filtration rate \> or = 60 mL/min/1.73m2
* Serum total bilirubin \< or = 1.5 mg/dL except for known Gilbert's disease
* Platelet count \> 100,000/µL
* Hemoglobin \> 9 g/dL
* Neutrophil granulocytes \> 1,500/mL
* International normalized ratio \< or = 2

Exclusion Criteria:

* Alcohol or drug abuse
* Inclusion in other trials interfering with the study protocol
* Chronic systemic immune therapy
* Chemotherapy or hormone therapy not indicated in the study protocol
* Severe organ insufficiency
* Pregnancy or breast feeding
* Appearance of distant metastases (liver, lung) of a CT scan of the abdomen of chest X-ray
* Severe or uncontrolled cardiac pathology
* \> 6 months occurrence of myocardial infarction
* Presence of congestive cardiac failure of symptomatic angor pectoris despite optimal medical treatment
* Presence of congestive cardiac failure of cardiac arrhythmia requiring medical treatment with insufficient rhythm control
* Uncontrolled arterial hypertension
* Active bacterial, viral or fungal infection
* Active gastrointestinal ulcer
* Any stage cirrhosis
* Uncontrolled diabetes mellitus
* Severe obstructive or restrictive respiratory insufficiency
* Tumor in the presence of obstruction
* Allergy to trial related drugs

Primary outcomes:
measure: Assessment of pharmacologic advantage
timeFrame: Day 2
measure: Assessment of Pt excretion in urine
timeFrame: day 2
measure: Assessment of efficacy in the tumor nodule as pharmacologic endpoint.
timeFrame: day 2
measure: Assessment of 3-month overall morbidity and mortality
timeFrame: During 3 months postoperative.
Secondary outcomes:
measure: Assessment of one-year overall survival
timeFrame: During one year postoperative.
measure: Assessment of health related quality of life (HRQOL): EORTC QLQ-C-30
timeFrame: Day 1
measure: Assessment of health related quality of life (HRQOL): SF-36
timeFrame: Day 1
measure: Assessment of health related quality of life (HRQOL): EORTC QLQ-C-30
timeFrame: up to 2 months
measure: Assessment of health related quality of life (HRQOL): SF-36
timeFrame: up to 2 months
measure: Assessment of health related quality of life (HRQOL): EORTC QLQ-C-30
timeFrame: month 3
measure: Assessment of health related quality of life (HRQOL): SF-36
timeFrame: month 3
Other outcomes:
Locations:
city: Genk
country: Belgium
facility: Ziekenhuis Oost-Limburg
Study officials:
References: