Colorectal CancerDPD côlonNCT01547923
Pre-therapeutic Identification of Dihydropyrimidine Dehydrogenase Gene (DPD) Deficiency for Predicting Toxicity to Fluoropyrimidines
A study testing Blood sample for phenotypic and pharmacogenetic analysis. in people with Colorectal Cancer and Intravenous 5 Fluorouracile, run by Institut Cancerologie de l'Ouest at 25 sites in France.
Trial summary
The aim of this study is to demonstrate the medical and financial benefit of pre-therapeutic screening of DPD deficiency for predicting toxicity to fluoropyrimidines. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer, Intravenous 5 Fluorouracile
- What is being tested?
- Blood sample for phenotypic and pharmacogenetic analysis.
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,142 participants
- Where
- 25 sitesFrance
- Study dates
- 16 Jun 2008to 4 Mar 2013
- 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
- colorectal cancer, histologically confirmed, with all types included (including adjuvant cases), requiring treatment with intravenous 5-fluorouracil.
- anterior chemotherapy authorised, with the exception of chemotherapy containing a derivate of 5-Fluorouracil
- Age > or = 18 years
- WHO Performance status < or = 2
- Haematologic and hepatic parameters : neutrophils > or = 1000 /mm3, platelets > or = 100000/mm3, Total bilirubin < or = 2 x ULN, AST and ALT < or = 3 x ULN, APL < or = 5 x ULN
- Complete initial assessment before first treatment administration for imaging and pharmacogenetic, within 15 days for biology, and within 7 days for clinical examination.
- Signed written informed consent
Who cannot join
- Prior chemotherapy with fluoropyrimidines
- Symptomatic or uncontrolled ventral nervous system metastases
- Psychiatric Disease disrupting the trial understanding and the enlightened and voluntary consent character
- Patient who is pregnant or breast feeding
- Woman not consenting to use adequate contraceptive precautions during the study
- Patient who can not submit itself to the formal follow-up for psychological, social, family or geographical reasons
- Significant serious pathology or any instable medical condition (cardiac pathology uncontrolled, myocardial infarction within 6 months before enrollment, systemic active uncontrolled infection)
- any investigational agent within 4 weeks before enrollment
Trial locations and contacts
25 sites in 1 country.
25 sites in 1 country
France25 sites
ICO Paul Papin
Angers, 49933
CHU Jean Minjoz
Besançon, 25000
CHU Morvan
Brest, 29609
CHU Côte de Nacre
Caen, 14033
Centre François Baclesse
Caen, 14076
Pôle Santé Léonard de Vinci
Chambray-lès-Tours, 37175
Centre Hospitalier du Haut Anjou
Château-Gontier, 53204
Centre Hospitalier
Cholet, 49325
Clinique des Cèdres
Cornebarrieu, 31700
Hôpital Henri Mondor
Créteil, 94010
CH Sarthe et Loir
La Flèche, 72205
Centre Hospitalier Les oudairies
La Roche-sur-Yon, 85929
Centre Hospitalier
Laval, 53015
Centre Hospitalier
Le Mans, 72037
Centre Oscar Lambret
Lille, 53020
Centre d'oncologie de Gentilly
Nancy, 54100
CHU Hotel Dieu
Nantes, 44093
Centre Antoine Lacassagne
Nice, 06189
HEGP
Paris, 75015
Centre Hospitalier Lyon Sud
Pierre-Bénite, 69495
ICO René Gauducheau
Saint-Herblain, 44805
Centre Hospitalier
Saumur, 49403
Institut Claudius Regaud
Toulouse, 31052
Hôpital Purpan
Toulouse, 31059
CHU Trousseau
Tours, 37044
About this study
Official title: The Medical-financial Evaluation of Pre-therapeutic Screening by a Joint Phenotypic-pharmacogenetic Approach for Metabolic Fluoropyrimidine Enzyme Deficiency in Terms of Serious Toxicity Risk Prevention : a Multicentric Case Study
The aim of this study is to demonstrate the medical and financial benefit of pre-therapeutic screening of DPD deficiency for predicting toxicity to fluoropyrimidines.
Read the detailed description
The fluoropyrimidines, of which 5-Fluorouracil is the most important, represent a family of medication that is used in particular in cancerology. They are molecules widely used in cancerology since they can be found in nearly 45% of chemotherapy protocols and in the treatment of about 50% of cancers (colorectum, oesophagus, stomach, breast, upper digestive and respiratory tracts). They are not only used in metastatic situations but also more and more in adjuvant situations, in other words for patients treated for a localised tumour, presenting a risk of relapse. A severe toxic risk cannot be tolerated in these conditions, and the doctor should assure the maximum level of safety for his patients. These medicines are the cause of 3% of grade IV toxicity from the first or second administration, and for 0.3% of deaths. To this one can add on a total of 20 to 25% grade III-IV toxic events.
Anticancer treatment is mostly administered by body size and in the best of cases after a few basic biological examinations such as a haemogram and renal status, without taking into consideration any individual particularities, whether genetic or epigenetic. Among potential toxicity risk factors one can find individual metabolic differences linked to genetic modifications of metabolism enzymes as well as differences in the chemical receptors and transporters.
For fluoropyrimidines, a polymorphism was found for the dihydropyrimidine dehydrogenase gene (DPD), a major catabolism enzyme. A deficit of this enzyme is a major counter-indication for the use of these medicines.
Early determination of DPD status would allow identification of patients at risk and would thus help in subsequent dose adjustment or selection of other treatment modalities.
- Conditions
- Colorectal Cancer, Intravenous 5 Fluorouracile
- Being tested
- Blood sample for phenotypic and pharmacogenetic analysis.
- Keywords
- Colorectal Cancer, DihydroPyrimidine Dehydrogenase, Lethal toxicity, Fluoropyrimidine
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood sample for phenotypic and pharmacogenetic analysis.Genetic
Prior to treatment by 5-FU, a DPD deficiency is identified thanks to just one blood sample (lithium heparinate).
Blood sample for phenotypic and pharmacogenetic analysis.Genetic
Blood sample (lithium heparinate) will be taken prior to treatment but not analysed.
| Study group | Role | What they receive |
|---|---|---|
| A : pre-therapeutic screening for DPD deficiency | Experimental | Prior to treatment by fluoropyrimidines,a DPD deficiency is identified by a joint phenotypic-pharmacogenetic approach. Receives: Genetic: Blood sample for phenotypic and pharmacogenetic analysis. |
| B : no pretherapeutic research of DPD deficiency | Other | For patients included in this arm, a blood sample will be taken prior to treatment by fluoropyrimidines but not analysed. If grade 3 or 4 toxicity levels are encountered during treatment, DPD deficiency will be detected. Receives: Genetic: Blood sample for phenotypic and pharmacogenetic analysis. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number and nature of grade IV toxicity.
The percentage of severe toxicity (grade IV) will be analyzed in each arm. We expect a reduction of the early, severe, grade IV acute side-effects from 3% to 0.6% in the detected group with adapted doses.
Measured: Up to 4 weeks.
Secondary outcomes (3)
Number of grade III-IV toxic events.
We expect a reduction of the number of grade III-IV toxic events, whenever they occur, from 25% to 5% in the detected group with adapted doses.
Measured: Up to 6 months.
Mortality rate.
The current mortality rate of 3 per thousand patients will be cut to 0 in the detected group with adapted doses.
Measured: up to 6 months.
Medical-financial study of pre-therapeutic screening.
We will carry out a comparison of the prevention costs and the costs related to treating patients with toxicity. Direct costs and indirect costs will be taken into account.
Measured: Up to 6 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2012 (estimated)
- Study start16 Jun 2008
- Primary completionMar 2013
- Study completion4 Mar 2013
Why it stopped: The study stopped due to a death in the arm control
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies 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 N/A
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,142 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut Cancerologie de l'Ouest
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Olivier Capitain, MD, PhD, Principal investigator, Institut Cancerologie de l'Ouest
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01547923
- Sponsor's protocol ID
- CPP-380
- Other IDs
- 2008-000026-39, 2008
- Acronym
- DPD côlon
- Status last verified
- Mar 2020
- First submitted
- 28 Feb 2012
- Last updated
- 25 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Medical-financial Evaluation of Pre-therapeutic Screening by a Joint Phenotypic-pharmacogenetic Approach for Metabolic Fluoropyrimidine Enzyme Deficiency in Terms of Serious Toxicity Risk Prevention : a Multicentric Case Study
- ClinicalTrials.gov ID
- NCT01547923
- Acronym / sponsor ID
- DPD côlon / CPP-380
- Conditions
- Colorectal Cancer, Intravenous 5 Fluorouracile
- Keywords
- Colorectal Cancer, DihydroPyrimidine Dehydrogenase, Lethal toxicity, Fluoropyrimidine
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study stopped due to a death in the arm control
- Enrolment
- 1,142 participants (actual)
- Lead sponsor
- Institut Cancerologie de l'OuestUniversity, hospital or other
- Study start
- 16 Jun 2008 (actual)
- Primary completion
- Mar 2013 (actual)
- Study completion
- 4 Mar 2013 (actual)
- First posted
- 8 Mar 2012 (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.
The aim of this study is to demonstrate the medical and financial benefit of pre-therapeutic screening of DPD deficiency for predicting toxicity to fluoropyrimidines.
Detailed description
The fluoropyrimidines, of which 5-Fluorouracil is the most important, represent a family of medication that is used in particular in cancerology. They are molecules widely used in cancerology since they can be found in nearly 45% of chemotherapy protocols and in the treatment of about 50% of cancers (colorectum, oesophagus, stomach, breast, upper digestive and respiratory tracts). They are not only used in metastatic situations but also more and more in adjuvant situations, in other words for patients treated for a localised tumour, presenting a risk of relapse. A severe toxic risk cannot be tolerated in these conditions, and the doctor should assure the maximum level of safety for his patients. These medicines are the cause of 3% of grade IV toxicity from the first or second administration, and for 0.3% of deaths. To this one can add on a total of 20 to 25% grade III-IV toxic events.
Anticancer treatment is mostly administered by body size and in the best of cases after a few basic biological examinations such as a haemogram and renal status, without taking into consideration any individual particularities, whether genetic or epigenetic. Among potential toxicity risk factors one can find individual metabolic differences linked to genetic modifications of metabolism enzymes as well as differences in the chemical receptors and transporters.
For fluoropyrimidines, a polymorphism was found for the dihydropyrimidine dehydrogenase gene (DPD), a major catabolism enzyme. A deficit of this enzyme is a major counter-indication for the use of these medicines.
Early determination of DPD status would allow identification of patients at risk and would thus help in subsequent dose adjustment or selection of other treatment modalities.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A : pre-therapeutic screening for DPD deficiency | Experimental | Genetic: Blood sample for phenotypic and pharmacogenetic analysis.Prior to treatment by fluoropyrimidines,a DPD deficiency is identified by a joint phenotypic-pharmacogenetic approach. |
| B : no pretherapeutic research of DPD deficiency | Other | Genetic: Blood sample for phenotypic and pharmacogenetic analysis.For patients included in this arm, a blood sample will be taken prior to treatment by fluoropyrimidines but not analysed. If grade 3 or 4 toxicity levels are encountered during treatment, DPD deficiency will be detected. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- colorectal cancer, histologically confirmed, with all types included (including adjuvant cases), requiring treatment with intravenous 5-fluorouracil.
- anterior chemotherapy authorised, with the exception of chemotherapy containing a derivate of 5-Fluorouracil
- Age > or = 18 years
- WHO Performance status < or = 2
- Haematologic and hepatic parameters : neutrophils > or = 1000 /mm3, platelets > or = 100000/mm3, Total bilirubin < or = 2 x ULN, AST and ALT < or = 3 x ULN, APL < or = 5 x ULN
Key exclusion criteria (8 listed)
- Prior chemotherapy with fluoropyrimidines
- Symptomatic or uncontrolled ventral nervous system metastases
- Psychiatric Disease disrupting the trial understanding and the enlightened and voluntary consent character
- Patient who is pregnant or breast feeding
- Woman not consenting to use adequate contraceptive precautions during the study
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 |
|---|---|---|
| Blood sample for phenotypic and pharmacogenetic analysis.Prior to treatment by 5-FU, a DPD deficiency is identified thanks to just one blood sample (lithium heparinate). | Genetic | A : pre-therapeutic screening for DPD deficiency |
| Blood sample for phenotypic and pharmacogenetic analysis.Blood sample (lithium heparinate) will be taken prior to treatment but not analysed. | Genetic | B : no pretherapeutic research of DPD deficiency |
Primary outcome
Number and nature of grade IV toxicity.
Time frame: Up to 4 weeks.
The percentage of severe toxicity (grade IV) will be analyzed in each arm. We expect a reduction of the early, severe, grade IV acute side-effects from 3% to 0.6% in the detected group with adapted doses.
3 secondary outcomes
Number of grade III-IV toxic events.
Time frame: Up to 6 months.
Mortality rate.
Time frame: up to 6 months.
Medical-financial study of pre-therapeutic screening.
Time frame: Up to 6 months.
Results and safety
The study was stopped early (reason given: The study stopped due to a death in the arm control). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2020.
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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.
Olivier Capitain, MD, PhD principal investigator
Institut Cancerologie de l'Ouest
25 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Blood sample for phenotypic and pharmacogenetic analysis. in people with Colorectal Cancer and Intravenous 5 Fluorouracile, run by Institut Cancerologie de l'Ouest at 25 sites in France.
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 7 inclusion and 8 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: stopped early, as of the sponsor's last update on 25 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in France. 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?
The study was stopped early (reason given: The study stopped due to a death in the arm control). 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?
Number and nature of grade IV toxicity. (time frame: Up to 4 weeks.). 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 25 Mar 2020.