Metastatic Colorectal CancerPhase 2/3NCT01523431
Individual Dosage Selection of Irinotecan (CPT-11) Based on UGT1A1 Genotype in Metastatic Colorectal Cancer Patients
A Phase 2/3 study testing Irinotecan Injection [Camptosar], 5-fluorouracil and Leucovorin in people with Metastatic Colorectal Cancer, run by The Affiliated Hospital of the Chinese Academy of Military Medical Sciences at 1 site in China.
Trial summary
The purpose of this study is to investigate the influence of dose selection of CPT-11 on toxicity, response and pharmacokinetics according to UGT1A1 genotype in colorectal cancer patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Irinotecan Injection [Camptosar], 5-fluorouracil and Leucovorin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 583 participants
- Where
- 1 siteChina
- Study dates
- 8 Mar 2012to 27 Apr 2016
- Phase
- Phase 2/3
- 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
- Histologically confirmed colorectal cancer patients who received no prior chemotherapy or failed to 1st line treatments
- At least one measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
- Aged 18 years or older
- ECOG performance status of ≤ 2.
- Anticipated life expectancy of ≥ 3 months.
- UGT1A1 genotype tested. Categorized into Wild (UGT1A1*1/*1), Hetero (UGT1A1*1/ *28, UGT1A1*1/ *6), and Homo (UGT1A1*28/*28, UGT1A1*6/*6, UGT1A1*28/*6).
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- Adequate organ function, including bone marrow, kidney and liver.
- ANC ≥ 1.5×109/L and hemoglobin ≥ 9g/dL and platelet count ≥ 100×109/L
- Serum total bilirubin ≤ 1.5 x ULN, alkaline phosphatase ≤ 2.5 x ULN, Serum ALT and AST ≤ 2.5 x ULN (Serum ALT and AST ≤ 5 x ULN, if liver metastases are present)
- Serum creatinine ≤ 1.5 x ULN or CLcr > 60 ml/min
- Written informed consent can be obtained prior to their participation in the trial.
Who cannot join
- Pregnant or breast feeding women.
- Subjects who have previously received CPT-11 treatment.
- Serious concurrent complication, severe active infection.
- Subjects with chronic diarrhea, acute or sub acute Intestinal obstruction.
- Subjects with uncontrolled CNS metastasis or epilepsia or severe psychiatric disorders.
- Subjects who are regarded to be unsuitable for this trial by the investigator.
- Subjects who are participating in other clinical trials.
Trial locations and contacts
1 site in 1 country.
China1 site
Affiliated Hospital Cancer Center, Academy of Military Medical Sciences (307 Hospital of PLA)
Beijing, Beijing Municipality, 100071
About this study
Official title: Influence of Individual Dosage Selection of Irinotecan (CPT-11) Based on UGT1A1 Genotype on Clinical Outcomes and Pharmacokinetics in Chinese Patients With Metastatic Colorectal Cancer
The purpose of this study is to investigate the influence of dose selection of CPT-11 on toxicity, response and pharmacokinetics according to UGT1A1 genotype in colorectal cancer patients.
Read the detailed description
Genetic polymorphisms of UGTs result in reduced enzyme activity and increased toxicity. UGT1A1*28 and UGT1A1*6 are reported to increase CPT-11-related toxicity in Asian patients. Moreover, the area under concentration curve (AUC) ratio of SN-38G to SN-38 is decreased in Asian patients having UGT1A1 *28 or UGT1A1*6. This implicated that the current standard dose of CPT-11 would be overdosing for homozygous UGT1A1*28/*28, *6/*6 or *28/*6 patients.
The study is designed to investigate the role of prospectively dose reduction of CPT-11 in toxicity, tumor response and pharmacokinetics for homozygous UGT1A1 patients, and compare these parameters to standard dose of CPT-11 for wild-type, heterozygous or homozygous UGT1A1 patients.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Irinotecan Injection [Camptosar], 5-fluorouracil, Leucovorin
- Keywords
- Colorectal cancer, Irinotecan, UGT1A1 genotype, Neutropenia, diarrhea, response, pharmacokinetic
- Medical subject headings
- Colorectal Neoplasms, Neutropenia, Diarrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Irinotecan Injection [Camptosar]Drug
Also called CPT-11, FOLFIRI regimen
CPT-11 will be administered according to UGT1A1 genotypes. Patients with UGT1A1 *1/*1 or heterozygous UGT1A1*1/*28 or *1/*6 will receive standard dose of CPT-11. Patients with homozygous UGT1A1*28/*28, *6/*6 or *28/*6, will be randomized in a 1:1 ratio to receive standard dose of CPT-11 or 50% reduced dose of CPT-11.
5-fluorouracilDrug
Also called 5-FU, FOLFIRI regimen
The 5-FU dosage will remain the standard.
LeucovorinDrug
Also called LV, FOLFIRI regimen
The LV dosage will remain the standard.
| Study group | Role | What they receive |
|---|---|---|
| Standard FOLFIRI for wild/hetero UGT1A1 | Active comparator | Irinotecan Injection [Camptosar] (CPT-11) 180 mg/m2, day 1; Leucovorin (LV) 400mg/m2, day 1; 5-fluorouracil (5-FU) 400mg/m2, day 1, 5-fluorouracil (5-FU) 2400mg/m2, day 1; Repeat every two weeks. Receives: Drug: Irinotecan Injection [Camptosar]; Drug: 5-fluorouracil; Drug: Leucovorin |
| Reduced Dose of CPT-11 for homo UGT1A1 | Experimental | Irinotecan Injection [Camptosar] (CPT-11) 90 mg/m2, day 1; Leucovorin (LV) 400mg/m2, day 1; 5-fluorouracil (5-FU) 400mg/m2, day 1, 5-fluorouracil (5-FU) 2400mg/m2, day 1; Repeat every two weeks. Receives: Drug: Irinotecan Injection [Camptosar]; Drug: 5-fluorouracil; Drug: Leucovorin |
| Standard FOLFIRI for homo UGT1A1 | Active comparator | Irinotecan Injection [Camptosar] (CPT-11) 180 mg/m2, day 1; Leucovorin (LV) 400mg/m2, day 1; 5-fluorouracil (5-FU) 400mg/m2, day 1, 5-fluorouracil (5-FU) 2400mg/m2, day 1; Repeat every two weeks. Receives: Drug: Irinotecan Injection [Camptosar]; Drug: 5-fluorouracil; Drug: Leucovorin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of toxicity, especially neutropenia and diarrhea
Association between UGT1A1 polymorphism, CPT-11 dosage and incidence of toxicity, especially neutropenia and diarrhea.
Measured: From the beginning of treatment to the whole treatment period, an expected average of 6-8 months.
Secondary outcomes (3)
Response rate
Association between UGT1A1 polymorphism, CPT-11 dosage and tumor response.
Measured: Every 6 weeks, an expected average of 6-8 months.
Progression-free survival (PFS)
Association between UGT1A1 polymorphism, CPT-11 dosage and PFS. PFS is defined as the length of time from randomise to disease progression or to death from any cause other than progression.
Measured: An expected average of 6-8 months.
Pharmacokinetics of irinotecan and its metabolites, SN-38 and SN-38G.
Association between UGT1A1 polymorphism, CPT-11 dosage and pharmacokinetics of irinotecan. Plasma concentration of irinotecan and its metabolites, SN-38 and SN-38G are determined using high-performance liquid chromatography-tandem mass spectrometry method (HPLC-MS/MS).
Measured: The first treatment cycle.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2012 (estimated)
- Study start8 Mar 2012
- Primary completion23 Nov 2015
- Study completion27 Apr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 583 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Affiliated Hospital of the Chinese Academy of Military Medical Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Xu jianming, The Affiliated Hospital of the Chinese Academy of Military Medical Sciences
- Investigators
- Jian-Ming Xu, M.D., Principal investigator, Affiliated Hospital, Academy of Military Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01523431
- Sponsor's protocol ID
- MCRC-307PLAH-XJM
- Status last verified
- Mar 2017
- First submitted
- 19 Jan 2012
- Last updated
- 30 Mar 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influence of Individual Dosage Selection of Irinotecan (CPT-11) Based on UGT1A1 Genotype on Clinical Outcomes and Pharmacokinetics in Chinese Patients With Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT01523431
- Acronym / sponsor ID
- MCRC-307PLAH-XJM
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- Colorectal cancer, Irinotecan, UGT1A1 genotype, Neutropenia, diarrhea, response, pharmacokinetic
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 583 participants (actual)
- Lead sponsor
- The Affiliated Hospital of the Chinese Academy of Military Medical SciencesUniversity, hospital or other
- Study start
- 8 Mar 2012 (actual)
- Primary completion
- 23 Nov 2015 (actual)
- Study completion
- 27 Apr 2016 (actual)
- First posted
- 1 Feb 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 purpose of this study is to investigate the influence of dose selection of CPT-11 on toxicity, response and pharmacokinetics according to UGT1A1 genotype in colorectal cancer patients.
Detailed description
Genetic polymorphisms of UGTs result in reduced enzyme activity and increased toxicity. UGT1A1*28 and UGT1A1*6 are reported to increase CPT-11-related toxicity in Asian patients. Moreover, the area under concentration curve (AUC) ratio of SN-38G to SN-38 is decreased in Asian patients having UGT1A1 *28 or UGT1A1*6. This implicated that the current standard dose of CPT-11 would be overdosing for homozygous UGT1A1*28/*28, *6/*6 or *28/*6 patients.
The study is designed to investigate the role of prospectively dose reduction of CPT-11 in toxicity, tumor response and pharmacokinetics for homozygous UGT1A1 patients, and compare these parameters to standard dose of CPT-11 for wild-type, heterozygous or homozygous UGT1A1 patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Standard FOLFIRI for wild/hetero UGT1A1 | Active comparator | Drug: Irinotecan Injection [Camptosar], Drug: 5-fluorouracil, Drug: LeucovorinIrinotecan Injection [Camptosar] (CPT-11) 180 mg/m2, day 1; Leucovorin (LV) 400mg/m2, day 1; 5-fluorouracil (5-FU) 400mg/m2, day 1, 5-fluorouracil (5-FU) 2400mg/m2, day 1; Repeat every two weeks. |
| Reduced Dose of CPT-11 for homo UGT1A1 | Experimental | Drug: Irinotecan Injection [Camptosar], Drug: 5-fluorouracil, Drug: LeucovorinIrinotecan Injection [Camptosar] (CPT-11) 90 mg/m2, day 1; Leucovorin (LV) 400mg/m2, day 1; 5-fluorouracil (5-FU) 400mg/m2, day 1, 5-fluorouracil (5-FU) 2400mg/m2, day 1; Repeat every two weeks. |
| Standard FOLFIRI for homo UGT1A1 | Active comparator | Drug: Irinotecan Injection [Camptosar], Drug: 5-fluorouracil, Drug: LeucovorinIrinotecan Injection [Camptosar] (CPT-11) 180 mg/m2, day 1; Leucovorin (LV) 400mg/m2, day 1; 5-fluorouracil (5-FU) 400mg/m2, day 1, 5-fluorouracil (5-FU) 2400mg/m2, day 1; Repeat every two weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Histologically confirmed colorectal cancer patients who received no prior chemotherapy or failed to 1st line treatments
- At least one measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
- Aged 18 years or older
- ECOG performance status of ≤ 2.
- Anticipated life expectancy of ≥ 3 months.
Key exclusion criteria (7 listed)
- Pregnant or breast feeding women.
- Subjects who have previously received CPT-11 treatment.
- Serious concurrent complication, severe active infection.
- Subjects with chronic diarrhea, acute or sub acute Intestinal obstruction.
- Subjects with uncontrolled CNS metastasis or epilepsia or severe psychiatric disorders.
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 |
|---|---|---|
| Irinotecan Injection [Camptosar]Also: CPT-11, FOLFIRI regimenCPT-11 will be administered according to UGT1A1 genotypes. Patients with UGT1A1 *1/*1 or heterozygous UGT1A1*1/*28 or *1/*6 will receive standard dose of CPT-11. Patients with homozygous UGT1A1*28/*28, *6/*6 or *28/*6, will be randomized in a 1:1 ratio to receive standard dose of CPT-11 or 50% reduced dose of CPT-11. | Drug | Reduced Dose of CPT-11 for homo UGT1A1, Standard FOLFIRI for homo UGT1A1, Standard FOLFIRI for wild/hetero UGT1A1 |
| 5-fluorouracilAlso: 5-FU, FOLFIRI regimenThe 5-FU dosage will remain the standard. | Drug | Reduced Dose of CPT-11 for homo UGT1A1, Standard FOLFIRI for homo UGT1A1, Standard FOLFIRI for wild/hetero UGT1A1 |
| LeucovorinAlso: LV, FOLFIRI regimenThe LV dosage will remain the standard. | Drug | Reduced Dose of CPT-11 for homo UGT1A1, Standard FOLFIRI for homo UGT1A1, Standard FOLFIRI for wild/hetero UGT1A1 |
Primary outcome
Incidence of toxicity, especially neutropenia and diarrhea
Time frame: From the beginning of treatment to the whole treatment period, an expected average of 6-8 months.
Association between UGT1A1 polymorphism, CPT-11 dosage and incidence of toxicity, especially neutropenia and diarrhea.
3 secondary outcomes
Response rate
Time frame: Every 6 weeks, an expected average of 6-8 months.
Progression-free survival (PFS)
Time frame: An expected average of 6-8 months.
Pharmacokinetics of irinotecan and its metabolites, SN-38 and SN-38G.
Time frame: The first treatment cycle.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2017.
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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.
Jian-Ming Xu, M.D. principal investigator
Affiliated Hospital, Academy of Military Medical Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Irinotecan Injection [Camptosar], 5-fluorouracil and Leucovorin in people with Metastatic Colorectal Cancer, run by The Affiliated Hospital of the Chinese Academy of Military Medical Sciences at 1 site in China.
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 11 inclusion and 7 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: finished, as of the sponsor's last update on 30 Mar 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 China. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Incidence of toxicity, especially neutropenia and diarrhea (time frame: From the beginning of treatment to the whole treatment period, an expected average of 6-8 months.). 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 30 Mar 2017.