Colorectal Peritoneal CarcinomatosisPhase 3COBOXNCT03028155
Concentration- Versus Body Surface Area-based HIPEC in Colorectal Peritoneal Carcinomatosis' Treatment
A Phase 3 study testing Oxaliplatin: BSA-based HIPEC and Oxaliplatin: Concentration-based HIPEC in people with Colorectal Peritoneal Carcinomatosis, run by Hasselt University at 1 site in Belgium.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Peritoneal Carcinomatosis
- What is being tested?
- Oxaliplatin: BSA-based HIPEC and Oxaliplatin: Concentration-based HIPEC
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteBelgium
- Study dates
- Nov 2016to Aug 2018
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Kurt Van der Speeten, prof. dr. contact
Lieselotte Lemoine, drs. contact
Belgium1 site, 1 recruiting
- Recruiting
Ziekenhuis Oost-Limburg
Genk, 3600
Lieselotte Lemoine, drs., lieselotte.lemoine@uhasselt.be
Kurt Van der Speeten, prof. dr.
About this study
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
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
- Being tested
- Oxaliplatin: BSA-based HIPEC, Oxaliplatin: Concentration-based HIPEC
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oxaliplatin: BSA-based HIPECDrug
oxaliplatin: 460 mg/m2 volume: dependent on the capacity of the peritoneal cavity of the patient
Oxaliplatin: Concentration-based HIPECDrug
oxaliplatin: 230 mg/L
| Study group | Role | What they receive |
|---|---|---|
| Oxaliplatin: BSA-based HIPEC | Active comparator | 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. Receives: Drug: Oxaliplatin: BSA-based HIPEC |
| Oxaliplatin: Concentration-based HIPEC | Active comparator | 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. Receives: Drug: Oxaliplatin: Concentration-based HIPEC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of pharmacologic advantage
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.
Measured: Day 2
Assessment of Pt excretion in urine
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.
Measured: day 2
Assessment of efficacy in the tumor nodule as pharmacologic endpoint.
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.
Measured: day 2
Assessment of 3-month overall morbidity and mortality
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.
Measured: During 3 months postoperative.
Secondary outcomes (7)
Assessment of one-year overall survival
One-year overall survival will be determined.
Measured: During one year postoperative.
Assessment of health related quality of life (HRQOL): EORTC QLQ-C-30
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.
Measured: Day 1
Assessment of health related quality of life (HRQOL): SF-36
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.
Measured: Day 1
Assessment of health related quality of life (HRQOL): EORTC QLQ-C-30
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.
Measured: up to 2 months
Assessment of health related quality of life (HRQOL): SF-36
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.
Measured: up to 2 months
Assessment of health related quality of life (HRQOL): EORTC QLQ-C-30
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
Measured: month 3
Assessment of health related quality of life (HRQOL): SF-36
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.
Measured: month 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2017 (estimated)
- Study startNov 2016
- Primary completionAug 2018 (estimated)
- Study completionAug 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal Peritoneal CarcinomatosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hasselt University
- Sponsor type
- University, hospital or other
- Collaborators
- Ziekenhuis Oost-Limburg
- Responsible party
- Principal investigator, Kurt Van der Speeten, Hasselt University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03028155
- Sponsor's protocol ID
- ZOLCOBOX1
- Acronym
- COBOX
- Status last verified
- Jan 2017
- First submitted
- 24 Dec 2016
- Last updated
- 23 Jan 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03028155
- Acronym / sponsor ID
- COBOX / ZOLCOBOX1
- Conditions
- Colorectal Peritoneal Carcinomatosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Hasselt UniversityUniversity, hospital or other
- Collaborators
- Ziekenhuis Oost-Limburg
- Study start
- Nov 2016
- Primary completion
- Aug 2018 (estimated)
- Study completion
- Aug 2018 (estimated)
- First posted
- 23 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Oxaliplatin: BSA-based HIPEC | Active comparator | Drug: Oxaliplatin: BSA-based HIPECIntervention: 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. |
| Oxaliplatin: Concentration-based HIPEC | Active comparator | Drug: Oxaliplatin: Concentration-based HIPECIntervention: 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oxaliplatin: BSA-based HIPECoxaliplatin: 460 mg/m2 volume: dependent on the capacity of the peritoneal cavity of the patient | Drug | Oxaliplatin: BSA-based HIPEC |
| Oxaliplatin: Concentration-based HIPECoxaliplatin: 230 mg/L | Drug | Oxaliplatin: Concentration-based HIPEC |
Primary outcome
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.
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.
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.
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.
7 secondary outcomes
Assessment of one-year overall survival
Time frame: During one year postoperative.
Assessment of health related quality of life (HRQOL): EORTC QLQ-C-30
Time frame: Day 1
Assessment of health related quality of life (HRQOL): SF-36
Time frame: Day 1
Assessment of health related quality of life (HRQOL): EORTC QLQ-C-30
Time frame: up to 2 months
Assessment of health related quality of life (HRQOL): SF-36
Time frame: up to 2 months
Assessment of health related quality of life (HRQOL): EORTC QLQ-C-30
Time frame: month 3
Assessment of health related quality of life (HRQOL): SF-36
Time frame: month 3
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2017.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kurt Van der Speeten, prof. dr. contact
Lieselotte Lemoine, drs. contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Oxaliplatin: BSA-based HIPEC and Oxaliplatin: Concentration-based HIPEC in people with Colorectal Peritoneal Carcinomatosis, run by Hasselt University at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kurt Van der Speeten, prof. dr. (kurt.vanderspeeten@zol.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of pharmacologic advantage (time frame: Day 2). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2017.