UMIN-CTR Clinical Trial

Public title

A multicenter phaseII study of FOLFIRI as FOLFOX refractory second-line chemotherapy for metastatic colorectal cancer with reduced starting dose of irinotecan in patients with honozygous for UGT1A1: (FLIGHT2)

Acronym

A multicenter phaseII study of second-line FOLFIRI for metastatic colorectal cancer(FLIGHT2)

Scientific Title

A multicenter phaseII study of FOLFIRI as FOLFOX refractory second-line chemotherapy for metastatic colorectal cancer with reduced starting dose of irinotecan in patients with honozygous for UGT1A1: (FLIGHT2)

Scientific Title:Acronym

A multicenter phaseII study of second-line FOLFIRI for metastatic colorectal cancer(FLIGHT2)

Region

Japan

Condition

colorectal cancer

Classification by specialty

Gastroenterology	Hematology and clinical oncology	Surgery in general
Gastrointestinal surgery

Classification by malignancy

Malignancy

Genomic information

YES

Narrative objectives1

To evaluate the tumor response rate, the incidence and severity of adverse events during second-line chemothrapy of FOLFIRI in patients with metastatic colorectal cancer.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Phase II

Primary outcomes

(1) response rate
(2) incidence and severity of adverse events

Key secondary outcomes

(1) overall survival (OS), progression-free survival (PFS)
(2) Evaluation of the causal relationship of each adverse event
(3) To investigate genetic variation of UGT1A1 and correlation with the toxicities of CPT-11

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

On Day 1, patients treated with FOLFIRI therapy received a 2-hour intravenous infusion of CPT-11 (150 mg/m2) combined with 1-LV (200 mg/m2), followed by a rapid intravenous infusion of 5-FU (400 mg/m2), and then a 46-hour continuous infusion of 5-FU (2,400 mg/m2). This regimen comprised one course of therapy and was repeated once every 2 weeks. Cycles of treatment will be continued for this study until disease progression (PD) occurs.
Patients will undergo UGT1A1 genotyping before starting to receive the protocol treatment. As recommended in the US prescribing information for Camptosar;, the starting dose of CPT-11 will be reduced to 100 mg/m2 in patients who are homozygous for the *28 allelic variant of UGT1A1 (further reduced to 75 mg/m2 in such patients aged 76-80 years). No dose adjustments will be made in patients who undergo UGT1A1 genotyping after starting to receive the protocol treatment.

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

80

years-old

>=

Gender

Male and Female

Key inclusion criteria

(1) Histopathologically proven colon carcinoma or rectal carcinoma.
(2) Advanced or recurrent disease that is not amenable to curative resection.
(3) Failure to first-line chemotherapy with FOLFOX.
(4) At least 2 weeks after the last course of FOLFOX.
(5) At least 4 weeks after surgery.
(6) ECOG performance status of 0-1.
(7) Age between 20 and 80 years.
(8) Life expectancy of at least 12 weeks.
(9) Presence of at least one measurable lesion (outside the radiation field). A measurable lesion is defined as one that can be measured in a single dimension by palpation (together with a scale-containing radiographic image that permits objective assessment of the lesion size), CT, MRI, or any other radiographic method and which has a larger diameter >=2 cm (or >=1 cm and >=twice the slice width when measured by MRI or spiral CT).
(10) Adequate function of vital organs (e.g., bone marrow, heart, lungs, liver, and kidneys), as demonstrated by laboratory data obtained within 14 days of enrollment that are in the following ranges:
White blood cell count: 3,000-12,000/mm3.
Neutrophil count: >=1,500/mm3
(calculated from the white blood cell count and the differential neutrophil count [%]).
Platelet count: >=100,000/mm3.
Serum bilirubin: =<1.50 mg/dL.
AST and ALT: =<100 IU/L or 100 U/L.
Serum creatinine: =<1.20 mg/dL.
(11) Written informed consent.

Key exclusion criteria

(1) Blood transfusion, administration of blood products, or hematopoietic (e.g., G-CSF) support within 7 days before enrollment.
(2) A history of severe drug allergy.
(3) Pleural effusion, ascites, or pericardial effusion requiring drainage.
(4) Active (e.g., clinically significant) infection.
(5) Confirmed or clinically suspected brain metastasis.*1
(6) Involvement of the central nervous system.
(7) Presence of bone metastasis as the sole metastasis.
(8) Any other concurrent malignancy, excluding metachronous malignancy that has been confirmed to have been cured.*2
(9) Uncontrolled hypercalcemia.
(10) Uncontrolled hypertension (despite antihypertensive medication).
(11) Uncontrolled diabetes mellitus.
(12) Any significant electrocardiographic abnormality or clinically significant heart disease.*3
(13) Fresh gastrointestinal bleeding.
(14) Intestinal paralysis or obstruction.
(15) Diarrhea (watery stools).*4
(16) Positivity for HIV antibody.
(17) Current treatment with atazanavir sulfate.
(18) Current treatment with phenytoin, warfarin potassium, or flucytosine.
(19) Pregnant or breast-feeding women, women of childbearing potential, women who wish to become pregnant, or men who wish to have a child with their female partners.
(20) Current participation in any other clinical trial/study.
(21) Any other condition that disqualifies the patient from the study in the opinion of the investigator.

Target sample size

50

Name of lead principal investigator

1st name
Middle name
Last name	Hideyuki Mishima

Organization

Aichi Medical University

Division name

Cancer Center

Zip code

Address

1-1, Yazakokarimata, Nagakute, Aichi

TEL

0561-62-3311

Email

hmishima@aichi-med-u.ac.jp

Name of contact person

1st name
Middle name
Last name	Mai Hatta

Organization

Nagoya University Graduate School of Medicine

Division name

Young Leaders&#39;Program

Zip code

Address

65 Tsurumai Showa-ku Nagoya

TEL

052-744-2442

Homepage URL

Email

m-hatta@med.nagoya-u.ac.jp

Institute

NPO Epidemiological and Clinical Research Information Network

Institute

Department

Personal name

Organization

NPO Epidemiological and Clinical Research Information Network

Organization

Division

Category of Funding Organization

Non profit foundation

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2009

Year

09

Month

10

Day

URL releasing protocol

Publication of results

Published

URL related to results and publications

Number of participants that the trial has enrolled

Results

RESULTS:

The overall response rate was 12% for all 50 evaluable patients; 31 patients (62.0%) had stable disease, and only in 12 (24.0%) did disease progress. The median progression-free survival was 5.8 months. The tolerance treatment was acceptable, with only 15 out of 50 patients (30%) experiencing grade 3/4 neutropenia, and grade 4 thrombocytopenia was observed in only one case. Grade 3 non-hematological adverse reactions included stomatitis in three, diarrhea in one, and a clinically insignificant increase in serum alkaline phosphatases in one patient, respectively. There was no definite relation between the UGT1A1*28 polymorphism and toxicity.

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2005

Year

10

Month

21

Day

Date of IRB

Anticipated trial start date

2006

Year

01

Month

01

Day

Last follow-up date

2009

Year

07

Month

01

Day

Date of closure to data entry

2009

Year

07

Month

01

Day

Date trial data considered complete

2009

Year

07

Month

01

Day

Date analysis concluded

2009

Year

07

Month

01

Day

Other related information

Anticancer Res. 2014 Jan;34(1):195-201.

Prospective phase II trial of second-line FOLFIRI in patients with advanced colorectal cancer including analysis of UGT1A1 polymorphisms: FLIGHT 2 study.

Hirata K, Nagata N, Kato T, Okuyama Y, Andoh H, Takahashi K, Oba K, Sakamoto J, Hazama S, Mishima H.

Registered date

2009

Year

09

Month

10

Day

Last modified on

2018

Year

09

Month

20

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000002872