Status Approved
First Submitted Date
2018/08/22
Registered Date
2018/10/19
Last Updated Date
2020/08/03
CRIS Required
WHO ICTRP (International Clinical Trial Registry Platform) Required
1. Background
CRIS Registration Number |
KCT0003278 |
---|---|
Unique Protocol ID | 4-2018-0460 |
Public/Brief Title | A study of bevacizumab, infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (A-FOLFOXIRI) compared with bevacizumab, infusional fluorouracil, leucovorin, and irinotecan/oxaliplatin (A-FOLFIRI/FOLFOX) as first-line treatment for metastatic right-sided colon cancer |
Scientific Title | A randomized, open-label, multicenter phase II study of bevacizumab, infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (A-FOLFOXIRI) compared with bevacizumab, infusional fluorouracil, leucovorin, and irinotecan/oxaliplatin (A-FOLFIRI/FOLFOX) as first-line treatment for metastatic right-sided colon cancer |
Acronym | |
MFDS Regulated Study | Yes |
IND/IDE Protocol | No |
Registered at Other Registry | No |
Healthcare Benefit Approval Status | Submitted approval |
2. Institutional Review Board / Ethics Committee
Board Approval Status | Submitted approval |
---|---|
Board Approval Number | 4-2018-0460 |
Approval Date | 2018-06-29 |
Institutional Review Board Name | Yonsei University Health System, Severance Hospital, Institutional Review Board |
Institutional Review Board Address | 50-1, Yonsei-ro, Seodaemun-gu, Seoul |
Institutional Review Board Telephone | 02-2228-0435 |
Data Monitoring Committee |
Yes
Independent Data-Monitoring Committee |
3. Contact Details
Contact Person for Principal Investigator / Scientific Queries | |
---|---|
Name | Joong Bae Ahn |
Title | M.D.,Ph.D |
Telephone | +82-2-2228-4320 |
Affiliation | Yonsei University Health System, Severance Hospital |
Address | 50-1 Yonsei-ro, Seodaemun-gu, Seoul |
Contact Person for Public Queries | |
Name | Hyon Jung Park |
Title | RN, CCRC |
Telephone | +82-2-2228-8054 |
Affiliation | Yonsei University Health System, Severance Hospital |
Address | 50-1 Yonsei-ro, Seodaemun-gu, Seoul |
Contact Person for Updating Information | |
Name | Hyon Jung Park |
Title | RN. CCRC |
Telephone | +82-2-2228-8054 |
Affiliation | Yonsei University Health System, Severance Hospital |
Address | 50-1 Yonsei-ro, Seodaemun-gu, Seoul |
4. Status
Study Site | Single | |
---|---|---|
Overall Recruitment Status | Recruiting | |
Date of First Enrollment | 2019-01-02 Actual | |
Target Number of Participant | 120 | |
Primary Completion Date | ||
Study Completion Date | ||
Recruitment Status by Participating Study Site 1 | ||
Name of Study | Yonsei University Health System, Severance Hospital | |
Recruitment Status | Recruiting | |
Date of First Enrollment | 2019-01-02 , |
5. Source of Monetary / Material Support
1. Source of Monetary/Material Support | |
---|---|
Organization Name | Boryung Pharm |
Organization Type | Pharmaceutical Company |
Project ID |
6. Sponsor Organization
1. Sponsor Organization | |
---|---|
Organization Name | Yonsei University Health System, Severance Hospital |
Organization Type | Medical Institute |
7. Study Summary
Lay Summary | RATIONALE: Recently, the importance of prognosis according to the location of the primary tumor in colorectal cancer has been raised. In the CALGB / SWOG 80405 study published in 2016, the addition of bevacizumab or cetuximab to the first line FOLFIRI / FOLFOX in KRAS (codon 12, 13) wild type metastatic colorectal cancer (mCRC) patients did not show a significant difference between overall survival (OS) and progression free survival (PFS) in both groups. Alan P. Venook et al. published a follow-up subgroup analysis on the effect of primary tumor location at 2016 ASCO. In the treatment group with cetuximab, the difference in treatment effect was significant according to the primary tumor location. The right colon cancer showed a poor prognosis for cetuximab treatment. (PFS: 7.8 vs 12.4 months, HR 1.56, p <0.0001 / OS: 16.7 vs 36.0months, HR 1.87, P <0.0001). Therefore, we propose a phase II trial for the efficacy evaluation of bevacizumab-FOLFOXIRI and bevacizumab-FOLFIRI or FOLFOX treatment in patients with poor prognosis of unresectable right-sided colorectal cancer. |
---|
8. Study Design
Study Type | Interventional Study |
---|---|
Study Purpose | Treatment |
Phase | Phase2 |
Intervention Model | Parallel |
Blinding/Masking | Open |
Allocation | RCT |
Intervention Type | Drug |
Intervention Description | Patients are stratified according to ECOG performance status (0 vs 1-2), prior adjuvant chemotherapy (yes vs no), and participating center. Patients are randomized to 1 of 2 treatment arms. Arm I (A-FOLFOXIRI): Patients receive irinotecan hydrochloride IV over 1 hour, oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and bevacizumab IV on day 1. Patients also receive fluorouracil IV continuously over 48 hours beginning on day 1. Arm II (A-FOLFOX/FOLFIRI): Patients receive irinotecan hydrochloride IV over 1 hour (or oxaliplatin IV over 2 hours), leucovorin calcium IV over 2 hours, flurorourcal IV bolus, and bevacizumab IV on day 1. Patients also receive fluorouracil IV continuously over 48 hours beginning on day 1. In both arms, treatment repeats every 2 weeks for up to 12 courses. After the 12 cycle treatment finished, investigator decides whether to keep the study drug. Treatment continues in the absence of disease progression, withdrawal consent, or unacceptable toxicity. If treatment with oxaliplatin or irinotecan is difficult due to side effects, treatment with bevacizumab, fluorouracil, and leucovorin calcium continues in the absence of disease progression, withdrawal consent, or unacceptable toxicity. |
Number of Arms | 2 |
Arm 1 |
Arm Label A-FOLFOX/A-FOLFIRI |
Target Number of Participant 60 |
|
Arm Type Active comparator |
|
Arm Description Patients receive irinotecan hydrochloride IV over 1 hour (or oxaliplatin IV over 2 hours), leucovorin calcium IV over 2 hours, flurorourcal IV bolus, and bevacizumab IV on day 1. Patients also receive fluorouracil IV continuously over 48 hours beginning on day 1. |
|
Arm 2 |
Arm Label A-FOLFOXIRI |
Target Number of Participant 60 |
|
Arm Type Experimental |
|
Arm Description Patients receive irinotecan hydrochloride IV over 1 hour, oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and bevacizumab IV on day 1. Patients also receive fluorouracil IV continuously over 48 hours beginning on day 1. |
9. Subject Eligibility
Condition(s)/Problem(s) |
* (C00-D48)Neoplasms (C18.2)Malignant neoplasm of ascending colon Colonic Neoplasms |
---|---|
Rare Disease | No |
Inclusion Criteria |
Gender Both |
Age 19Year~No Limit |
|
Description 1) Histologically proven diagnosis of unresectable recurrent or advanced stage IV right-sided colon cancer (The definition of the right colon cancer is confirmed by the colonoscopy result, the surgical report, or the image reading paper including CT, MRI, and PET CT. (cecum~splenic flexure)) 2) Not previously treated with chemotherapy for metastatic disease 3) At least one measurable lesion according to Response evaluation criteria in solid tumors criteria 4) Age over 19 years old 5) Eastern Cooperative Oncology Group (ECOG) Performance Status 0~2 6) Life expectancy of at least 3 months 7) Adequate major organ functions 8) Absolute neutrophil count ≥ 1.5 x 109/L 9) Platelet ≥ 100 x 109/L 10) hemoglobin ≥ 9.0 g/dL (can be corrected by blood transfusion) 11) Total bilirubin ≤ upper normal limit(UNL) * 1.5 12) Aspartate transaminase, Alanine transaminase≤ UNL * 3 (in case of liver metastasis, Aspartate transaminase, Alanine transaminase≤ UNL * 5), alkaline phosphatase ≤ UNL *3 (in case of liver metastasis, ALP ≤ UNL * 5 13) adequate renal function : corrected creatinine clearance by Cockcroft and Gault formula ≥ 30mL/min 14) Urine dipstick of proteinuria <2+. Patients discovered to have 2+ proteinuria on dipstick urinalysis at baseline, should undergo a 24-hour urine collection and must demonstrate 1 g of protein/24 hr. 15) Written informed consent. |
|
Exclusion Criteria |
1) Previously treated with chemotherapy for metastatic disease 2) Within 6 months after adjuvant chemotherapy 3) Major surgical procedure within 28 days prior to study treatment start, or patients who have not fully recovered from major surgery 4) Radiotherapy to target lesion within 4 weeks before the study (A 2-week washout is permitted for palliative radiation.) 5) Has known uncontrolled active CNS metastases and/or carcinomatous meningitis 6) Peripheral neuropathy Common Terminology Criteria for Adverse Events v4.03 ≥ grade 2 7) Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of skin, squamous cell carcinoma of the skin, low grade thyroid cancer or carcinoma in situ (eg, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. 8) Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy, such as thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, is not considered a form of systemic systemic treatment and is allowed. 9) Uncontrolled hyeprtension or clinically active cardiovascular disease: for example, cerebrovascular accident or transient isschemic attack, unstable angina, myocaridal infarction within 24 weeks prior to randomization. Have symptomatic congestive heart failure (CHF; New York Heart Association II-IV) or symptomatic or poorly controlled cardiac arrhythmia. 10) Have significant bleeding disorders, or evidence of bleeding diathesis or coagulopathy 11) have had a significant bleeding episode from the gastrointestinal (GI) tract or lung 12) Have a history of GI perforation and/or fistula, or intraabominal abscess within 24 weeks prior to randomization. 13) Have a history of Hereditary nonpolyposis colorectal cancer syndrome or polyposis 14) Have experienced any arterial thromboembolic event or ongoing treatment with anticoagulants for therapeutic purpose within 24 weeks prior to randomization. 15) Has a known history of human immunodeficiency virus (HIV) infection 16) Are pregnant or breast feeding. Females of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to first dose of study treatment. For women of childbearing potential and men, agreement to remain abstinent or use contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 30 days after the last dose of study drugs. Postmenopausal women is defined that : - must have been amenorrheic for at least 12 months, > 50 years old or - Age ≤ 50 years old and amenorrheic for 12 or more months in the abscence of chemotherapy, tamoxifen, toremifene, or ovarian suppression and follicle-stimulating hormone (FSH) and estradiol in the postmenopausal range (>40 mIU/mL) - prior bilateral oophorectomy 17) Patients who are hypesenstivie reaction to experimental drugs 18) Patients who are hypersensitive to CHO(Chinese Hamster Ovary) cell products or other recombinant or humanized antibodies 19) In case of contraindication of experimental drugs 20) Have any condition (eg, psychological, geographical, or medical) that does not permit compliance with the study and follow-up procedures or suggest that the patient is, in the investigator’s opinion, not an appropriate candidate for the study. |
Healthy Volunteers | No |
10. Outcome Measure(s)
Type of Primary Outcome | /Safety/Efficacy | |
---|---|---|
Primary Outcome(s) 1 | ||
Outcome | 6-months progression-free survival rate |
|
Timepoint | 6 months |
|
Secondary Outcome(s) 1 | ||
Outcome | adverse event |
|
Timepoint | every 2 weeks |
11. Study Results and Publication
Result Registered | No |
---|
12. Sharing of Study Data(Deidentified Individual-Patient Data, IPD)
Sharing Statement | No |
---|
TOP
BOTTOM
화면 최하단으로 이동