T-CORE1201 Phase II trial of bi-weekly cetuximab plus mFOLFOX6 or cetuximab plus mFOLFIRI for unresectable advanced or recurrent KRAS wild type colorectal cancer and exploratory research of biomarker predicting effect of the treatment

JRCT ID: jRCTs021180014

Registered date:25/03/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: colorectal cancer
• Date of first enrollment: 07/06/2012
• Target sample size: 66
• Study type: Interventional

Intervention(s)

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 me

Outcome(s)

• Primary Outcome: Median progression free survival (PFS)
• Secondary Outcome: Overall response rate (ORR) and the frequency and grades of adverse effects.

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include 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

Exclude 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

Related Information

• Primary Sponsor: Ishioka Chikashi
• Source(s) of Monetary Support: Tohoku Clinical Oncology Research and Education Society (T-CORE)
• Secondary ID(s): UMIN000008298