Colon CancerNCT02959541
PK/PD Investigation of Calciumfolinat in Blood, Tumor and Adjacent Mucosa in Patient With Colon Cancer
A study testing Leucovorin in people with Colon Cancer and Chemotherapy, run by Vastra Gotaland Region at 1 site in Sweden.
Trial summary
This is an open randomized single site Pharmacokinetic and Pharmacodynamic study,of Calciumfolinat 60 mg/m², 200 mg/m² or 500 mg/ m² in blood, tumor and adjacent mucosa from patients with colon cancer Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colon Cancer, Chemotherapy
- What is being tested?
- Leucovorin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteSweden
- Study dates
- Sep 2016to 31 Dec 2022
- Phase
- Interventional
- 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
- Patients must have an operable colon cancer that is determined to colorectal surgery
- Patients must sign an informed consent document
- Patients must be ≥ 18 years of age
- Fertile women must present a negative pregnancy test and use secure contraceptives during and three months after treatment
Who cannot join
- Neo-adjuvant chemotherapy within the last 30 days
- Presence of clinically relevant (i.e., detectable by physical examination) third-space fluid collection (e.g., ascites, pleural effusion) that cannot be controlled by drainage or other procedures prior to study entry
- Female patients: currently pregnant or breast-feeding
- Patient with epileptic medication, such as fenobarbital, primidon, fenytoin och succinimider
Trial locations and contacts
1 site in 1 country.
Sweden1 site
Department of surgery, Östra, Sahlgrenska University Hospital
Gothenburg, 416 85
About this study
Official title: An Open Randomized Single Site Pharmacokinetic and Pharmacodynamic Study, of Calciumfolinat 60 mg/m², 200 mg/m² or 500 mg/ m² in Blood, Tumor and Adjacent Mucosa From Patients With Colon Cancer
This is an open randomized single site Pharmacokinetic and Pharmacodynamic study,of Calciumfolinat 60 mg/m², 200 mg/m² or 500 mg/ m² in blood, tumor and adjacent mucosa from patients with colon cancer
Read the detailed description
Cytotoxic treatment of patients with colorectal cancer (CRC) includes most various different drugs but 5-fluorouracil (5-FU) is the cornerstone in most regimens. Leucovorin (LV) is frequently used as a part of a standard treatment regime for advanced CRC in combination with 5-FU. In numerous randomized clinical trials the addition of LV to 5-FU has been shown to significantly improve the antitumor activity and to prolong the survival of patients receiving adjuvant chemotherapy or treatment for advanced disease as to compared to treatment with 5-FU as single drug therapy.
In most European countries 5-FU is given as an infusion during 46 hours in combination with a two hour infusion of LV. This regime is called the deGramont schedule. In the Nordic countries, 5-FU and LV are often given as bolus injections according to the regime called Nordic FLV. Leucovorin is a prodrug which has to be metabolized to methylenetetrahydrofolate (mTHF) in order to increase inhibition of the target enzyme thymidylate synthase (TS). Due to the low concentrations of the reduced folate forms intracellular there is a lack of knowledge of the pharmacodynamics of LV when used as an infusion. When the 5-FU/LV used today was introduced it was technically not possible to measure the different metabolites of the reduced folates in blood and tissue. In the literature there is only one published reference measuring the blood concentration after a two hour infusion of LV. However, it has recently been possible to separate and quantitate the different folates using sensitive Liquid Chromatography/Masspectrometry (LC/MS) methods. Furthermore it has been stated that differences in enzyme activity for genes involved in the transport and metabolism of folates may be responsible for the large inter individual differences in folate tissue concentrations.
This study is designed to gain an understanding of how a single intravenous infusion of LV affects the folate concentration in blood, tumor and adjacent mucosa tissue. By using the LC/MS method which was recently developed and it is now possible to quantitate the different metabolites of LV in small tissue samples as well as in blood. It is further now possible to measure by quantitative Polymerase Chain Reaction techniques (PCR) the most important genes involved in the folate transport and metabolism ((SHMT1), SerineHydroxyMethylTransferase1 and (ABCC3) ATP-binding cassette, sub-family C, (CFTR/MRP), member 3)).
- Conditions
- Colon Cancer, Chemotherapy
- Being tested
- Leucovorin
- Keywords
- Leukovorin
- Medical subject headings
- Colonic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LeucovorinDrug
Also called Calciumfolinat is the brandname of Leucovorin
| Study group | Role | What they receive |
|---|---|---|
| Calciumfolinat 60 mg/m² | Other | Intravenous infusion of Calciumfolinat 60 mg/m²given to patients with colon cancer at the time for the operation of the colon cancer. Receives: Drug: Leucovorin |
| Calciumfolinat 200 mg/m² | Other | Intravenous infusion of Calciumfolinat 200 mg/m² given to patients with colon cancer at the time for the operation of the colon cancer. Receives: Drug: Leucovorin |
| Calciumfolinat 500 mg/ m² | Other | Intravenous infusion of Calciumfolinat 500 mg/ m² given to patients with colon cancer at the time for the operation of the colon cancer. Receives: Drug: Leucovorin |
What is being measured
The primary outcome is the main question the study is designed to answer.
[6R] 5,10-methylene-THF - tumor
Tissue concentration of [6R] 5,10-methylene-THF in the tumor
Measured: First day during surgery
[6R] 5,10-methylene-THF - adjacent mucosa
Tissue concentration of [6R] 5,10-methylene-THF in adjacent mucosa
Measured: First day during surgery
5-formyl-THF - tumor
Tissue concentration of 5-formyl-THF in the tumor
Measured: First day during surgery
5-formyl-THFin - adjacent mucosa
Tissue concentration of 5-formyl-THFin the adjacent mucosa
Measured: First day during surgery
5-methyl-THF - tumor
Tissue concentration of 5-methyl-THF in the tumor
Measured: First day during surgery
5-methyl-THF - adjacent mucosa
Tissue concentration of 5-methyl-THF in the adjacent mucosa
Measured: First day during surgery
THF - tumor
Tissue concentration of THF in the tumor
Measured: First day during surgery
THF - adjacent mucosa
Tissue concentration of THF in the adjacent mucosa
Measured: First day during surgery
Secondary outcomes (7)
AUC [6R] 5,10-methylene-THF
AUC(0-24h) calculated from plasma concentration of [6R] 5,10-methylene-THF
Measured: Up to 24 hours
AUC 5-formyl-THF
AUC(0-24h) calculated from plasma concentration of 5-formyl-THF (if data
Measured: Up to 24 hours
AUC 5-methyl-THF
AUC(0-24h) calculated from plasma concentration of 5-methyl-THF (if data permits)
Measured: Up to 24 hours
AUC THF
AUC(0-24h) calculated from plasma concentration of THF (if data permits)
Measured: Up to 24 hours
Correlation AUC - blood and tissue
Correlation between AUC calculated from blood concentration and tissue concentration in the tumor and adjacent mucosa
Measured: Up to 24 hours
Gene expression - correlation to tissue concentration of the reduced folates
Gene expression in the tumor and correlation to tissue concentration of the reduced folates
Measured: First day during surgery
Gene expression - correlation adjacent mucosa tissue concentration of the reduced folates
Gene expression in the adjacent mucosa and correlation to tissue concentration of the reduced folates
Measured: First day during surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2016 (estimated)
- Study startSep 2016
- Primary completion26 May 2020
- Study completion31 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colon CancerStudies of the same condition, open and under way.
- More trials run by Vastra Gotaland RegionThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vastra Gotaland Region
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Elinor Bexe Lindskog, MD, PhD, Principal investigator, Sahlgrenska University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02959541
- Sponsor's protocol ID
- 00068128
- Status last verified
- Sep 2021
- First submitted
- 20 Oct 2016
- Last updated
- 13 Jun 2022
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Randomized Single Site Pharmacokinetic and Pharmacodynamic Study, of Calciumfolinat 60 mg/m², 200 mg/m² or 500 mg/ m² in Blood, Tumor and Adjacent Mucosa From Patients With Colon Cancer
- ClinicalTrials.gov ID
- NCT02959541
- Acronym / sponsor ID
- 00068128
- Conditions
- Colon Cancer, Chemotherapy
- Keywords
- Leukovorin
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Vastra Gotaland RegionOther government
- Study start
- Sep 2016 (actual)
- Primary completion
- 26 May 2020 (actual)
- Study completion
- 31 Dec 2022 (estimated)
- First posted
- 9 Nov 2016 (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.
This is an open randomized single site Pharmacokinetic and Pharmacodynamic study,of Calciumfolinat 60 mg/m², 200 mg/m² or 500 mg/ m² in blood, tumor and adjacent mucosa from patients with colon cancer
Detailed description
Cytotoxic treatment of patients with colorectal cancer (CRC) includes most various different drugs but 5-fluorouracil (5-FU) is the cornerstone in most regimens. Leucovorin (LV) is frequently used as a part of a standard treatment regime for advanced CRC in combination with 5-FU. In numerous randomized clinical trials the addition of LV to 5-FU has been shown to significantly improve the antitumor activity and to prolong the survival of patients receiving adjuvant chemotherapy or treatment for advanced disease as to compared to treatment with 5-FU as single drug therapy.
In most European countries 5-FU is given as an infusion during 46 hours in combination with a two hour infusion of LV. This regime is called the deGramont schedule. In the Nordic countries, 5-FU and LV are often given as bolus injections according to the regime called Nordic FLV. Leucovorin is a prodrug which has to be metabolized to methylenetetrahydrofolate (mTHF) in order to increase inhibition of the target enzyme thymidylate synthase (TS). Due to the low concentrations of the reduced folate forms intracellular there is a lack of knowledge of the pharmacodynamics of LV when used as an infusion. When the 5-FU/LV used today was introduced it was technically not possible to measure the different metabolites of the reduced folates in blood and tissue. In the literature there is only one published reference measuring the blood concentration after a two hour infusion of LV. However, it has recently been possible to separate and quantitate the different folates using sensitive Liquid Chromatography/Masspectrometry (LC/MS) methods. Furthermore it has been stated that differences in enzyme activity for genes involved in the transport and metabolism of folates may be responsible for the large inter individual differences in folate tissue concentrations.
This study is designed to gain an understanding of how a single intravenous infusion of LV affects the folate concentration in blood, tumor and adjacent mucosa tissue. By using the LC/MS method which was recently developed and it is now possible to quantitate the different metabolites of LV in small tissue samples as well as in blood. It is further now possible to measure by quantitative Polymerase Chain Reaction techniques (PCR) the most important genes involved in the folate transport and metabolism ((SHMT1), SerineHydroxyMethylTransferase1 and (ABCC3) ATP-binding cassette, sub-family C, (CFTR/MRP), member 3)).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Calciumfolinat 60 mg/m² | Other | Drug: LeucovorinIntravenous infusion of Calciumfolinat 60 mg/m²given to patients with colon cancer at the time for the operation of the colon cancer. |
| Calciumfolinat 200 mg/m² | Other | Drug: LeucovorinIntravenous infusion of Calciumfolinat 200 mg/m² given to patients with colon cancer at the time for the operation of the colon cancer. |
| Calciumfolinat 500 mg/ m² | Other | Drug: LeucovorinIntravenous infusion of Calciumfolinat 500 mg/ m² given to patients with colon cancer at the time for the operation of the colon cancer. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients must have an operable colon cancer that is determined to colorectal surgery
- Patients must sign an informed consent document
- Patients must be ≥ 18 years of age
- Fertile women must present a negative pregnancy test and use secure contraceptives during and three months after treatment
Key exclusion criteria (4 listed)
- Neo-adjuvant chemotherapy within the last 30 days
- Presence of clinically relevant (i.e., detectable by physical examination) third-space fluid collection (e.g., ascites, pleural effusion) that cannot be controlled by drainage or other procedures prior to study entry
- Female patients: currently pregnant or breast-feeding
- Patient with epileptic medication, such as fenobarbital, primidon, fenytoin och succinimider
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 |
|---|---|---|
| LeucovorinAlso: Calciumfolinat is the brandname of Leucovorin | Drug | Calciumfolinat 200 mg/m², Calciumfolinat 500 mg/ m², Calciumfolinat 60 mg/m² |
Primary outcome
[6R] 5,10-methylene-THF - tumor
Time frame: First day during surgery
Tissue concentration of [6R] 5,10-methylene-THF in the tumor
[6R] 5,10-methylene-THF - adjacent mucosa
Time frame: First day during surgery
Tissue concentration of [6R] 5,10-methylene-THF in adjacent mucosa
5-formyl-THF - tumor
Time frame: First day during surgery
Tissue concentration of 5-formyl-THF in the tumor
5-formyl-THFin - adjacent mucosa
Time frame: First day during surgery
Tissue concentration of 5-formyl-THFin the adjacent mucosa
5-methyl-THF - tumor
Time frame: First day during surgery
Tissue concentration of 5-methyl-THF in the tumor
5-methyl-THF - adjacent mucosa
Time frame: First day during surgery
Tissue concentration of 5-methyl-THF in the adjacent mucosa
THF - tumor
Time frame: First day during surgery
Tissue concentration of THF in the tumor
THF - adjacent mucosa
Time frame: First day during surgery
Tissue concentration of THF in the adjacent mucosa
7 secondary outcomes
AUC [6R] 5,10-methylene-THF
Time frame: Up to 24 hours
AUC 5-formyl-THF
Time frame: Up to 24 hours
AUC 5-methyl-THF
Time frame: Up to 24 hours
AUC THF
Time frame: Up to 24 hours
Correlation AUC - blood and tissue
Time frame: Up to 24 hours
Gene expression - correlation to tissue concentration of the reduced folates
Time frame: First day during surgery
Gene expression - correlation adjacent mucosa tissue concentration of the reduced folates
Time frame: First day during surgery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jun 2022.
Related trials for Colon Cancer
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 2
Tislelizumab in People With Colorectal Cancer
Colorectal Cancer
Not yet recruitingPhase 2
Alberta Cancer Exercise Dose in Colorectal Cancer
Cancer, Colorectal Cancer
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.
Elinor Bexe Lindskog, MD, PhD principal investigator
Sahlgrenska University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Leucovorin in people with Colon Cancer and Chemotherapy, run by Vastra Gotaland Region at 1 site in Sweden.
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 4 inclusion and 4 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 13 Jun 2022. 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 Sweden. 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.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
[6R] 5,10-methylene-THF - tumor (time frame: First day during surgery). The study lists 8 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 13 Jun 2022.