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

January 19, 2017 updated by: Kurt Van der Speeten, Hasselt University

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: 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.
Drug: Oxaliplatin: BSA-based HIPEC
oxaliplatin: 460 mg/m2 volume: dependent on the capacity of the peritoneal cavity of the patient
Active Comparator: 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.
Drug: Oxaliplatin: Concentration-based HIPEC
oxaliplatin: 230 mg/L

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Assessment of pharmacologic advantage
Time Frame: Day 2

the area-under-the-curve (AUC) ratio of the intraperitoneal (IP) exposure over the AUC of the intravenous (IV) exposure to oxaliplatin. Intraoperative sampling of plasma and peritoneal fluid at seven time points (0, 5, 10, 15, 20, 25 and 30 minutes) during the 30-minute HIPEC procedure.

The concentration of oxaliplatin will be determined in plasma and peritoneal fluid by means of a validated inductively coupled plasma mass spectrometry (ICP-MS). A concentration versus time curve will be set-up and the AUC will be determined.
Day 2
Assessment of Pt excretion in urine
Time Frame: day 2
Intraoperative sampling of urine at seven time points (0, 5, 10, 15, 20, 25 and 30 minutes) during the 30-minute HIPEC procedure. The concentration of oxaliplatin will be determined in urine by means of a validated ICP-MS. A concentration versus time curve will be set-up and the AUC will be determined.
day 2
Assessment of efficacy in the tumor nodule as pharmacologic endpoint.
Time Frame: day 2
At the day of surgery (day 2): intraoperative sampling of tumor nodules at seven time points (0, 5, 10, 15, 20, 25 and 30 minutes) during the 30-minute HIPEC procedure. The concentration of oxaliplatin will be determined in tumor nodules by means of a validated ICP-MS. A concentration versus time curve will be set-up and the AUC will be determined.
day 2
Assessment of 3-month overall morbidity and mortality
Time Frame: During 3 months postoperative.
Morbidity and mortality will be evaluated using the Clavien-Dindo classification. This classification consists of five grades: grade I, deviation from standard post-operative course within 'allowed therapeutic regimens'; grade II, complication requiring surgical, endoscopic or radiological intervention; grade IV, complication requiring ICU admission and grade V, complication resulting in death.
During 3 months postoperative.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Assessment of one-year overall survival
Time Frame: During one year postoperative.
One-year overall survival will be determined.
During one year postoperative.
Assessment of health related quality of life (HRQOL): EORTC QLQ-C-30
Time Frame: Day 1
HRQOL will be determined by means of the EORTC QLQ-C-30 (version 3.0, 2001). This questionnaire is developed to evaluate quality of life (QOL) of cancer patients, translated and validated in Dutch. Scoring will be according to manufacturer's guidelines, EORTC scoring manual.
Day 1
Assessment of health related quality of life (HRQOL): SF-36
Time Frame: Day 1
HRQOL will be determined by means of the 36-item Short Form Survey (SF-36). This questionnaire is developed by RAND Health. Scoring will be according to instructions form RAND Health.
Day 1
Assessment of health related quality of life (HRQOL): EORTC QLQ-C-30
Time Frame: up to 2 months
HRQOL will be determined by means of the EORTC QLQ-C-30 (version 3.0, 2001). This questionnaire is developed to evaluate quality of life (QOL) of cancer patients, translated and validated in Dutch. Scoring will be according to manufacturer's guidelines, EORTC scoring manual.
up to 2 months
Assessment of health related quality of life (HRQOL): SF-36
Time Frame: up to 2 months
HRQOL will be determined by means of the 36-item Short Form Survey (SF-36). This questionnaire is developed by RAND Health. Scoring will be according to instructions form RAND Health.
up to 2 months
Assessment of health related quality of life (HRQOL): EORTC QLQ-C-30
Time Frame: month 3
HRQOL will be determined by means of the EORTC QLQ-C-30 (version 3.0, 2001). This questionnaire is developed to evaluate quality of life (QOL) of cancer patients, translated and validated in Dutch. Scoring will be according to manufacturer's guidelines, EORTC scoring manual
month 3
Assessment of health related quality of life (HRQOL): SF-36
Time Frame: month 3
HRQOL will be determined by means of the 36-item Short Form Survey (SF-36). This questionnaire is developed by RAND Health. Scoring will be according to instructions form RAND Health.
month 3

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hasselt University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Ziekenhuis Oost-Limburg

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2016

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2018

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 24, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 19, 2017

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 23, 2017

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 23, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 19, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ZOLCOBOX1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Colorectal Peritoneal Carcinomatosis

Clinical Trials on Oxaliplatin: BSA-based HIPEC

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings