Individual Dosage Selection of Irinotecan (CPT-11) Based on UGT1A1 Genotype in Metastatic Colorectal Cancer Patients

NCT ID: NCT01523431

Last Updated: 2017-03-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

583 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-03-08

Study Completion Date

2016-04-27

Brief Summary

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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

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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

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Metastatic Colorectal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Standard FOLFIRI for wild/hetero UGT1A1

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.

Group Type ACTIVE_COMPARATOR

Irinotecan Injection [Camptosar]

Intervention Type DRUG

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-fluorouracil

Intervention Type DRUG

The 5-FU dosage will remain the standard.

Leucovorin

Intervention Type DRUG

The LV dosage will remain the standard.

Reduced Dose of CPT-11 for homo UGT1A1

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.

Group Type EXPERIMENTAL

Irinotecan Injection [Camptosar]

Intervention Type DRUG

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-fluorouracil

Intervention Type DRUG

The 5-FU dosage will remain the standard.

Leucovorin

Intervention Type DRUG

The LV dosage will remain the standard.

Standard FOLFIRI for homo UGT1A1

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.

Group Type ACTIVE_COMPARATOR

Irinotecan Injection [Camptosar]

Intervention Type DRUG

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-fluorouracil

Intervention Type DRUG

The 5-FU dosage will remain the standard.

Leucovorin

Intervention Type DRUG

The LV dosage will remain the standard.

Interventions

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Irinotecan Injection [Camptosar]

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.

Intervention Type DRUG

5-fluorouracil

The 5-FU dosage will remain the standard.

Intervention Type DRUG

Leucovorin

The LV dosage will remain the standard.

Intervention Type DRUG

Other Intervention Names

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CPT-11 FOLFIRI regimen 5-FU FOLFIRI regimen LV FOLFIRI regimen

Eligibility Criteria

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Inclusion Criteria

1. Histologically confirmed colorectal cancer patients who received no prior chemotherapy or failed to 1st line treatments
2. At least one measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
3. Aged 18 years or older
4. ECOG performance status of ≤ 2.
5. Anticipated life expectancy of ≥ 3 months.
6. 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).
7. 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
8. Written informed consent can be obtained prior to their participation in the trial.

Exclusion Criteria

1. Pregnant or breast feeding women.
2. Subjects who have previously received CPT-11 treatment.
3. Serious concurrent complication, severe active infection.
4. Subjects with chronic diarrhea, acute or sub acute Intestinal obstruction.
5. Subjects with uncontrolled CNS metastasis or epilepsia or severe psychiatric disorders.
6. Subjects who are regarded to be unsuitable for this trial by the investigator.
7. Subjects who are participating in other clinical trials.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The Affiliated Hospital of the Chinese Academy of Military Medical Sciences

OTHER

Sponsor Role lead

Responsible Party

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Xu jianming

Director of Department of GI Cancer

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jian-Ming Xu, M.D.

Role: PRINCIPAL_INVESTIGATOR

Affiliated Hospital, Academy of Military Medical Sciences

Locations

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Affiliated Hospital Cancer Center, Academy of Military Medical Sciences (307 Hospital of PLA)

Beijing, Beijing Municipality, China

Site Status

Countries

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China

Other Identifiers

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MCRC-307PLAH-XJM

Identifier Type: -

Identifier Source: org_study_id

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