UMIN-CTR Clinical Trial

Public title

Phase II trial of bi-weekly cetuximab plus mFOLFOX6 or cetuximab plus mFOLFIRI for unresectable advanced or recurrent KRAS wild type colorectal cancer (T-CORE1201)

Acronym

Phase II trial of bi-weekly cetuximab plus mFOLFOX6 or cetuximab plus mFOLFIRI for unresectable advanced or recurrent KRAS wild type colorectal cancer (T-CORE1201)

Scientific Title

Phase II trial of bi-weekly cetuximab plus mFOLFOX6 or cetuximab plus mFOLFIRI for unresectable advanced or recurrent KRAS wild type colorectal cancer (T-CORE1201)

Scientific Title:Acronym

Phase II trial of bi-weekly cetuximab plus mFOLFOX6 or cetuximab plus mFOLFIRI for unresectable advanced or recurrent KRAS wild type colorectal cancer (T-CORE1201)

Region

Japan

Condition

colorectal cancer

Classification by specialty

Gastroenterology	Hematology and clinical oncology	Gastrointestinal surgery

Classification by malignancy

Malignancy

Genomic information

YES

Narrative objectives1

Primary endpoint is to evaluate median progression free survival (PFS) of cetuximab plus mFOLFOX6 or cetuximab plus mFOLFIRI as second line therapy in unresectable advanced or recurrent KRAS wild type colorectal cancer patients. Secondary endpoint is to estimate overall response rate (ORR) and the frequency and grades of adverse effects.
In addition, the correlation between the clinical efficacy of chemotherapy and the biomarker in tissue specimen of patients participating in this study are evaluated. Further, to verify or predictable about the effectiveness of cetuximab by sub-type classification by comprehensive gene expression analysis.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Phase II

Primary outcomes

Median progression free survival (PFS)

Key secondary outcomes

Overall response rate (ORR) and the frequency and grades of adverse effects.

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

Patients who received L-OHP based chemotherapy as 1st line therapy are allocated bi-weekly cetuximab plus mFOFIRI. Patients who received CPT-11 based chemotherapy as 1st line therapy are allocated bi-weekly cetuximab plus mFOLFOX. Cetuximab is administered by 2 hours infusion before mFOLFOX or mFOFIRI. mFOLFOX: 85 mg/m2 of oxaliplatin, 200 mg/m2 of l-leucovorin, 400 mg/m2 of 5-FU by rapid intravenous (IV) infusion on day 1 and 2,400 mg/m2 of 5-FU for 46 h by continuous IV infusion as a 2-week course.
mFOLFIRI: 150 mg/m2 of irinotecan, 200 mg/m2 of l-leucovorin, 400 mg/m2 of 5-FU by rapid intravenous (IV) infusion on day 1 and 2,400 mg/m2 of 5-FU for 46 h by continuous IV infusion as a 2-week course.
The treatment was continued until the criteria to discontinue the trial were met.

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

Not applicable

Gender

Male and Female

Key inclusion criteria

The criteria for eligibility were as follows:
1) Written informed consent was obtained from the patient for trial participation.
2) Patient of pathologically defined colorectal adenocarcinoma.
3) Surgical specimen or biopsy specimens are available.
4) WT KRAS is confirmed.
5) Age 20 or older.
6) Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1.
7) One or more measurable lesions based on the RECIST (ver 1.1) are confirmed by CT within 30 days before registration. In case of patient who received radiation therapy, new measurable lesions after radiation therapy or measurable lesions out of radiation field.
8) Patient who received L-OHP based or CPT-11 based chemotherapy and confirmed refractory or intolerable. In case of patient who receieved adjuvant chemotherapy more than six months since last administration, the adjuvant chemotherapy is not defined as 1st line chemotherapy.
9) Following interval from previous treatments (4 weeks from radiations, 2weeks from a operation with some organ resection(excluding colostomy), 2 weeks from chemotherapy, 2 weeks from hormone therapy and immunotherapy, 2 weeks from cytokine therapy and BRM drugs, 4 weeks from other clinical trial).
10) Survival is expected to be at least 60 days or more.
11) No obvious organ failures and satisfy the following laboratory data within 15 days before registration:
1. Neutrophiles: 1,500/mm3 or more.
2. Hb: 8.0 g/dl or more.
3. Platelets: 100,000/mm3 or more.
4. Total bilirubin: less than 2.0 mg/dl.
5. AST(GOT) and ALT(GPT): 100 IU/L or less.
6. Serum creatinine: 1.50 mg/dL or less.

Key exclusion criteria

The exclusion criteria were as follows;
1) Patients who treated transfusion, such as blood products and G-CSF treatment within 7 days before registration.
2) History of severe drug hypersensitivity or allergy.
3) In case of receiving bi-weekly cetuximab plus mFOLFOX, history of severe drug hypersensitivity or allergy with L-OHP.
4) Obvious infection and inflammation (fever with 38.0 degree or higher).
5) Poorly controlled hypercalcemia.
6) Poorly controlled hypertension.
7) Poorly controlled diabetes.
8) Obvious abnormality in ECG or heart disease becomes a clinical problem.
9) Severe pulmonary disease such as interstitial pneumonia, pulmonary fibrosis, severe emphysema.
10) Patient with a mental disorder becomes a clinical problem or a history of a CNS disorder.
11) Active GI tract bleeding.
12) Patient who need drainage of peritoneal, pleural or pericardial effusion.
13) Patient who have wide range bone metastases.
14) Patient who has or clinically suspicious for brain metastasis.
15) Chronic diarrhea may disturb the daily life(watery diarrhea).
16) Gastrointestinal paresthesia and bowel obstruction.
17) Active double cancer.
18) Patients who are treated with atazanavir sulfate.
19) Grade 3 or more hypersensitivity with monoclonal antibody.
20) Patients who were treated with EGFR or EGFR pathway targeted therapy.
21) Patients who are addicted to alcohol or drugs.
22) HBs antigen positive or active hepatitis B.
23) Peripheral sensory neuropathy interfering with daily life.
24) Women who are pregnant, may be pregnant, wish to become pregnant or are lactating. Men who wish their partner to become pregnant.
25) Attending physician determines that the case was inappropriate as the subject of this study.

Target sample size

100

Name of lead principal investigator

1st name	Chikashi
Middle name
Last name	Ishioka

Organization

Institute of Development, Aging and Cancer, Tohoku University

Division name

Department of Clinical Oncology

Zip code

980-8575

Address

4-1, Seiryo-Machi, Aoba-ku, Sendai City, Miyagi

TEL

022-717-8543

Email

chikashi@tohoku.ac.jp

Name of contact person

1st name	Masanobu
Middle name
Last name	Takahashi

Organization

Tohoku Clinical Oncoogy, Research and Education Society(T-CORE)

Division name

Administration Office

Zip code

980-8575

Address

4-1 Seiryo-machi, Aoba-ku, Sendai,9808575, Japan

TEL

0227178599

Homepage URL

https://t-core.jp

Email

toruishi@t-core.jp

Institute

Tohoku Clinical Oncoogy, Research and Education Society(T-CORE)

Institute

Department

Personal name

Organization

Tohoku Clinical Oncoogy, Research and Education Society(T-CORE)

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Tohoku University

Address

1-1 Seiryo-machi, Aoba-ku, Sendai 9808574, Japan

Tel

022(717)7000

Email

med-kenkyo@bureau.tohoku.ac.jp

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

2012

Year

06

Month

29

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

66

Results

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

2012

Year

03

Month

10

Day

Date of IRB

2012

Year

02

Month

27

Day

Anticipated trial start date

2012

Year

06

Month

01

Day

Last follow-up date

2020

Year

03

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2012

Year

06

Month

29

Day

Last modified on

2020

Year

07

Month

07

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000009444