Clinical trial NCT02246049: A Multicenter, Clinical Study of FOLFOXIRI With Bevacizumab As First-line Therapy in Patients With mCRC
Official title: A Multicenter, Clinical Phase II Study of FOLFOXIRI With Bevacizumab As First-line Therapy in Patients With Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Neoplasms
Keywords: Metastatic colorectal cancer, bevacizumab, FOLFOXIRI
Lead sponsor: EPS Corporation
Sponsor class: OTHER
First posted: 2014-09-22
Enrollment: 69
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study to assess efficacy and tolerability of combination therapy FOLFOXIRI with Bevacizumab (BV) as a first-line therapy in patients with metastatic colorectal cancer.

Detailed description: This is a single-arm, multicentre phase II study evaluating the efficacy and safety of Bevacizumab (BV) in combination with oxaliplatin, irinotecan hydrochloride, fluorouracil, and leucovorin calcium regimen ( FOLFOXIRI +BV ; Falcone et al. ASCO2013) as first-line treatment for Japanese metastatic colorectal cancer patients.

This study is composed two steps because of collecting safety issue in Japanese patient.

As First step (Step 1), It assess on the initial safety information in ten Japanese patients of the end of 2nd cycle. it is evaluated by DMC.

In parallel with the confirmation of the initial safety issue, register up to 65 cases in total and Step 1 patient, to evaluate the efficacy and safety (Step2).

Eligibility criteria: Inclusion Criteria:

1. Written Informed consent.
2. Histopathologically proven diagnosis of colorectal cancer (adenocarcinoma) excluding vermiform appendix cancer and proctos cancer.
3. Not resectable metastatic colorectal cancer
4. Age at enrollment is \>= 20 and \<= 75 years
5. ECOG PS \< 2 if age \< 70 years, ECOG PS = 0 if age = 71-75 years
6. One or more measurable lesion in RECIST ver.1.1 criteria according to contrast enhanced CT chest / abdomen / pelvis diagnosis.
7. Not previously treated with chemotherapy. ( Previous adjuvant by fluoropyrimidine monotherapy is allowed if more than 24 weeks have elapsed between the end of adjuvant therapy and first relapse.)
8. Vital organ functions (listed below) are preserved within 2 weeks prior to entry. Data recorded nearest to the entry should be referred. Blood transfusion or erythropoiesis stimulating agents less than 2 weeks prior to the tests are not allowed.

   Neu. \>= 1,500/cubicmillimeter Pt. \>= 100,000/cubicmillimeter Hb. \>= 9.0 g/dL T-bil. \<= upper limit of normal (ULN)\*1.5 AST and ALT,ALP \<= upper limit of normal (ULN)\*2.5 (\<= ULN\*5 in case of liver metastasis) Serum creatinine \<= upper limit of normal (ULN) \*1.5 PT-INR \< 1.5 Proteinuria \<= 2+
9. UGT1A1 genotype tested. Categorized into Wild or single Hetero.

Exclusion Criteria:

1. Previously treated with irradiation to bone marrow constituting 20% or more of irradiation field.
2. Untreated brain metastases or spinal cord compression or primary brain tumors.
3. History of CNS disease.\[except for asymptomatic Lacunar stroke\]
4. Requiring chronic systemic corticosteroid treatment.
5. Current or recent ongoing treatment with anticoagulants.
6. Clinically significant cardiovascular disease for example cerebrovascular accidents, myocardial infarction, unstable angina, congestive heart failure, serious cardiac arrhythmia requiring medication.
7. Treatment with any investigational drug within 4 weeks.
8. Patient with Uncontrolled hypertension, Uncontrolled diabetes, Uncontrolled diarrhea, \>=grade 1 peripheral neuropathy, Active peptic ulcer, Non-healing wound, Clinically important diseases.
9. Major surgical procedure within 28 days prior to study treatment start, open biopsy, or significant traumatic injury, or anticipation of the need for major surgical procedure.\[except for implantation of central venous catheter and port system.\]
10. Lack of physical integrity of the upper gastrointestinal tract.
11. Pregnant women, lactating woman , positive by pregnancy test , wishing to become pregnant, and Sexually active males.
12. Hepatitis B or hepatitis C. Evidence of HIV infection.
13. Previous Chemotherapy for other organs.
14. Other active co-existing malignancies.
15. History / Presence of thrombosis within 1 year requiring medication.
16. History / Presence of paralytic ileus, obstruction or gastrointestinal perforation.
17. Malignant coelomic fluid required drainage.
18. History of allergy to Chinese hamster ovary cell proteins, or any of the components of the study medications.
19. History of fluoropyrimidine severe side effects caused by DPD defect.
20. Interstitial pneumonitis or pulmonary fibrosis.
21. Evidence or requiring systemic treatment for Infectious disease.
22. Patient who is judged by the investigator to be inappropriate for study participation for any reason.

Primary outcomes:
measure: Progression-free survival (PFS) at 10 months
timeFrame: PFS rate at 10 months from study entry
Secondary outcomes:
measure: Response rate (RR) by central review.
timeFrame: Up to 18 months
measure: Response rate (RR) by investigator-reported measurements.
timeFrame: Up to 30 months
measure: PFS by central review according to CT image.
timeFrame: Up to 18 months
measure: Overall survival (OS)
timeFrame: Up to 30 months
measure: Efficacy by RAS status ; RR,PFS,OS
timeFrame: Up to 30 months
measure: Incidence of adverse events
timeFrame: Up to 30 months
measure: Time to treatment-failure
timeFrame: Up to 30 months
measure: Completion rate in Induction treatment
timeFrame: Up to 30 months
measure: Relative Dose Intensity
timeFrame: Up to 30 months
measure: Treatment duration
timeFrame: Up to 30 months
Other outcomes:
Locations:
city: Shinjuku
country: Japan
facility: EPS Corporation
state: Tokyo
Study officials:
affiliation: Department of Surgery, National Hospital Organization Osaka National Hospital.
name: Takeshi Kato, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Surgery, Shimane Prefectural Central Hospital.
name: Akiyoshi Kanazawa, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
References: