Concentration- Versus Body Surface Area-based HIPEC in Colorectal Peritoneal Carcinomatosis' Treatment

NCT ID: NCT03028155

Last Updated: 2017-01-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-30
• Study Completion Date: 2018-08-31

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.

Conditions

Colorectal Peritoneal Carcinomatosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Oxaliplatin: BSA-based HIPEC

Intervention: oxaliplatin: BSA-based HIPEC HIPEC will be performed using oxaliplatin as chemotherapeutic agent at a dose of 460 mg/m2 mixed in 0.9% saline carrier solution during 30 minutes. Volume of the carrier solution: depended on the capacity of the abdominal cavity of the patient.

Group Type: ACTIVE_COMPARATOR

Oxaliplatin: BSA-based HIPEC

Intervention Type: DRUG

oxaliplatin: 460 mg/m2 volume: dependent on the capacity of the peritoneal cavity of the patient

Oxaliplatin: Concentration-based HIPEC

Intervention: oxaliplatin: concentration-based HIPEC HIPEC will be performed using oxaliplatin as chemotherapeutic agent at a dose of 460 mg/m2 mixed in 0.9% saline carrier solution at 2L/m2, which equals a concentration of 230 mg/L during 30 minutes.

Group Type: ACTIVE_COMPARATOR

Oxaliplatin: Concentration-based HIPEC

Intervention Type: DRUG

oxaliplatin: 230 mg/L

Interventions

Oxaliplatin: BSA-based HIPEC

oxaliplatin: 460 mg/m2 volume: dependent on the capacity of the peritoneal cavity of the patient

Intervention Type: DRUG

Oxaliplatin: Concentration-based HIPEC

oxaliplatin: 230 mg/L

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ziekenhuis Oost-Limburg

OTHER

Sponsor Role: collaborator

Hasselt University

OTHER

Sponsor Role: lead

Responsible Party

Kurt Van der Speeten

prof. dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Ziekenhuis Oost-Limburg

Genk, , Belgium

Site Status: RECRUITING

Countries

Belgium

Central Contacts

Kurt Van der Speeten, prof. dr.

Role: CONTACT

kurt.vanderspeeten@zol.be

Lieselotte Lemoine, drs.

Role: CONTACT

lieselotte.lemoine@uhasselt.be

Facility Contacts

Lieselotte Lemoine, drs.

Role: primary

lieselotte.lemoine@uhasselt.be

Other Identifiers

ZOLCOBOX1

Identifier Type: -

Identifier Source: org_study_id