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

NCT01523431 | Completed Phase 2 FDA Drug

• 1 other identifier: MCRC-307PLAH-XJM
• Study Type: interventional
• Target: 583
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Metastatic Colorectal Cancer

Keywords

Colorectal cancer; Irinotecan; UGT1A1 genotype; Neutropenia; diarrhea; response; pharmacokinetic

Outcome Measures

Primary Outcomes (1)

• Incidence of toxicity, especially neutropenia and diarrhea

  Association between UGT1A1 polymorphism, CPT-11 dosage and incidence of toxicity, especially neutropenia and diarrhea.

  From the beginning of treatment to the whole treatment period, an expected average of 6-8 months.

Secondary Outcomes (3)

• Response rate

  Every 6 weeks, an expected average of 6-8 months.

• Progression-free survival (PFS)

  An expected average of 6-8 months.

• Pharmacokinetics of irinotecan and its metabolites, SN-38 and SN-38G.

  The first treatment cycle.

Study Arms (3)

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.

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.

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.

Drug: Irinotecan Injection [Camptosar]; Drug: 5-fluorouracil; Drug: Leucovorin

Interventions

Irinotecan Injection [Camptosar] 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.

Also known as: CPT-11, FOLFIRI regimen

Reduced Dose of CPT-11 for homo UGT1A1; Standard FOLFIRI for homo UGT1A1; Standard FOLFIRI for wild/hetero UGT1A1

5-fluorouracil DRUG

The 5-FU dosage will remain the standard.

Also known as: 5-FU, FOLFIRI regimen

Reduced Dose of CPT-11 for homo UGT1A1; Standard FOLFIRI for homo UGT1A1; Standard FOLFIRI for wild/hetero UGT1A1

Leucovorin DRUG

The LV dosage will remain the standard.

Also known as: LV, FOLFIRI regimen

Reduced Dose of CPT-11 for homo UGT1A1; Standard FOLFIRI for homo UGT1A1; Standard FOLFIRI for wild/hetero UGT1A1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The Affiliated Hospital of the Chinese Academy of Military Medical Sciences: lead

Study Sites (1)

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

Beijing, Beijing Municipality, 100071, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Neutropenia; Diarrhea

Interventions

Irinotecan; Fluorouracil; Leucovorin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Agranulocytosis; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• Jian-Ming Xu, M.D.

  Affiliated Hospital, Academy of Military Medical Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Department of GI Cancer

Study Record Dates

• First Submitted: January 19, 2012
• First Posted: February 1, 2012
• Study Start: March 8, 2012
• Primary Completion: November 23, 2015
• Study Completion: April 27, 2016
• Last Updated: March 30, 2017

Record last verified: 2017-03

Locations

CN (1)