FOLFIRINOX for 2nd-line Treatment of BTC
关键词
抽象
描述
The 5-FU/leucovorin/irinotecan (FOLFIRI) therapy, along with the capecitabine/irinotecan therapy, is reported as the most commonly used secondary chemotherapy in the AGEO group in France. A treatment strategy for continuous use of FOLFIRI as a secondary treatment after the failure of Gemcitabine/oxaliplatin showed the median value for OS period of 21.9 months, and the median value for the PFS period. The PFS and OS due to the FOLFIRI was found to be 3.2 months and 8.4 months, respectively. On the other hand, the FOLFOX therapy, which combines oxaliplatin with 5-FU, showed a response rate of 21.6 % when administered as a secondary treatment after the failure of gemcitabine/cisplatin, and a median PFS of 3.1 months. A phase III study is currently underway that compares the administration of FOLFOX as a secondary treatment with the optimum support. In Korea, there is a problem with the standard reimbursement for applying to drugs prescribed to cancer patients, and in particular, cancer drugs that can be used as secondary therapy in metastatic BTC patients are limited. There is a need to improve the prognosis of BTC patients by expanding the use of various drugs that have been proven through external clinical research.
<5-FU, leucovorin, irinotecan, and oxaliplatin combination chemotherapy (FOLFIRINOX) regimen for other cancer of BTC> In a pre-clinical experiment, oxaliplatin and irinotecan have synergistic effects and are known to have relatively no overlap of toxic effects among, 5-FU, leucovorin, irinotecan, and oxaliplatin. The combination treatment of 5-FU/leukovorin/irinotecan/oxaliplatin (FOLFIRINOX) had a high therapeutic effect on progressive pancreatic cancer and colon cancer. In a phase III study comparing FOLFIRINOX and gemcitabine as a first line treatment in metastatic pancreatic cancer, the objective response rate (32 vs. 9%), PFS (6.4 vs. 3.3 months) and OS (11.1 vs. 6.8 months) were significantly higher in FOLFIRINOX. On the other hand, treatment-related toxicities, with a grade 3/4 of neutropenia (46 vs. 21%), febrile neutropenia (5.4 vs. 1.2%), thrombocytopenia (9.1 vs. 3.6%), sensory neuropathy (9 vs. 0%), vomiting (23 vs. 18%), and diarrhea (113 vs. 2%) were more common in FOLFIRINOX [17]. In a phase III study comparing the 5-FU/leukovorin/irinotecan/oxaliplatin(FORFOXRI) and the 5-FU/leukovorin/irinotecan(FORFIRI) as a first line treatment in metastatic colorectal cancer, the FORFOXRI group was objective response (66 vs. 41 %), the PFS (9.8 vs. 6.9 months) and the OS (2.6 vs. 16.7 months) showed significant improvements. In pancreatic cancer, FOLFIRINOX was a treatment that was limited in patients with good general condition due to its high level of toxicity, including neutropenia, but the dose-reduction proved to be applied not only as a primary treatment but also as a secondary treatment. In a phase II study of pancreatic cancer patients in China, there was a 29% of grade 3/4 neutropenia were reported due to the treatment of modified FOLFIRINOX using oxaliplatin 68 mg/m2, irinotecan 135 mg/m2, and 5-FU injection of 2,400 mg/m2 for 46 hours, and there was no increase in mortality and febrile neutropenia. Other major grade 3 or higher toxicity levels showed improved safety profiles with thrombocytopenia (4.8%), anemia (8.1%), infection (4.8%), and elevated liver enzyme (14.5%).
As a 2nd line treatment for metastatic BTC the assessment of modified FOLFIRINOX is supported by:
- The prognosis for metastatic BTC, which fails first line therapy, is poor and has no standardized treatment. Therefore, better treatment modalities are required to improve the survival of patients who no longer respond to first line treatment and to maintain the quality of life.
- Treatments that use irinotecan or oxaliplatin as secondary therapy for metastatic BTC have been shown in retrospective and phase II studies and are actually used in clinical practice of other countries.
- Oxaliplatin and irinotecan have synergistic effects and the FOLFIRINOX therapy, which uses both drugs together in 5-FU/leucovorin, has been shown to increase efficacy in pancreatic and colon cancer.
- The modified FOLFIRINOX, which was used with reduced dosage, indicates an acceptable toxic profile while maintaining its efficacy
日期
最后验证: | 11/30/2018 |
首次提交: | 12/11/2018 |
提交的预估入学人数: | 12/13/2018 |
首次发布: | 12/18/2018 |
上次提交的更新: | 12/13/2018 |
最近更新发布: | 12/18/2018 |
实际学习开始日期: | 02/28/2019 |
预计主要完成日期: | 02/28/2021 |
预计完成日期: | 02/28/2022 |
状况或疾病
干预/治疗
Drug: mFOLFIRINOX
Drug: mFOLFIRINOX
Drug: mFOLFIRINOX
Drug: mFOLFIRINOX
相
手臂组
臂 | 干预/治疗 |
---|---|
Experimental: mFOLFIRINOX D1 Oxaliplatin 65 mg/m2 + 5% dextrose water (5DW) 200 mL mix IV over 2 hours followed by, D1 Leucovorin 400 mg/m2 + 5DW 200 ml mix IV over 2 hours D1 Irinotecan 135 mg/m2 + 5DW 500 mL mix IV over 2 hours (concurrent with the leucovorin infusion) D1-2 5-Fluorouracil 1000 mg/m2 + 5DW 1 liter (1L) continuous IV over 23 hours repeat every 2 weeks | Drug: mFOLFIRINOX D1-2 5-Fluorouracil 1000 mg/m2 + 5DW 1L continuous IV over 23 hours q 2 weeks |
资格标准
有资格学习的年龄 | 20 Years 至 20 Years |
有资格学习的性别 | All |
接受健康志愿者 | 是 |
标准 | Inclusion Criteria: 1. Histologically confirmed BTC (cholangiocarcinoma or gall bladder (GB) cancer) , except ampulla of Vater cancer 2. In the event that the progression of the gemcitabine/cisplatin is experienced during or after discontinuation of the first line treatment for metastatic, locally advanced or relapsed (it may be considered as a first line treatment that recurrence within six months of completion of the adjuvant or neo-adjuvant chemotherapy using gemcitabine/cisplatin) 3. Patient (or legal representative) has completed an approved consent documents that he or she will participate in the test after receiving sufficient information about the clinical trial 4. East clinical oncology group (ECOG) performance status 0-1 5. One or more measurable lesions by RECIST v1.1. 6. Appropriate organ functions; A. Liver: bilirubin ≤ 3 mg/dL, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 x ULN (in cases of liver metastasis, AST or ALT ≤ 5 x ULN) B. Kidney: An estimate of creatine clearance rate according to the Cockcroft-Gault formula (or local institution's standard method) > 30 mili-liter (mL)/min C. Hemoglobin ≥ 9 g/dL (transfusion allowed), absolute neutrophil count (ANC) ≥ 1500/μL, platelet count ≥ 75,000/μL. 7. Expected life time over 3 months. 8. Over 19 years old. 9. In case of proper bile excretion function 10. Have the will and ability to comply with the clinical trial plan during the study period, including treatment and scheduled visits and examination. 11. For pre-menopausal women and for women less than one year after the onset of menopause, serum or urine pregnancy tests shall be confirmed negative during screening. 12. For men and fertile women, the use of effective contraceptive methods should be agreed (effective contraception should be used for at least 30 days prior to the initial administration of a investigational drug, the trial period, and at least 90 days after the discontinuation of the test participation). Exclusion Criteria: 1. ≥ 2 of prior chemotherapy for progressive BTC (except for adjuvant/neo-adjuvant chemotherapy with resting of more than six months) 2. Symptomatic or untreated brain metastasis or spinal cord compression metastasis. 3. Previous treatment using Irinotecan or oxaliplatin 4. In case of major surgery within four weeks just before registration, excluding biopsy for diagnosis 5. In case of chemotherapy or radiation therapy was received within three weeks prior to the administration of a test medication 6. Grade 2 or higher peripheral neuropathy 7. Grade 2 or higher toxicities caused by a previous cancer treatment based on NCI-CTCAE v 4.03 other than hair loss 8. A person diagnosed with another malignant tumor within the last five years. Exceptions include basal or squamous cell carcinoma of the skin or intraepithelial neoplasia (bladder, uterine cervical, colorectal, breast) 9. Pregnant or nursing woman 10. If there is a severe or uncontrolled systemic disease, active infection, active bleeding tendency or organ transplantation history (including allo-hematopoietic stem cell transplantation) 11. The following virus infection A. Known positive history for human immunodeficiency virus (Human Immunodeficiency virus, HIV) test or known acquired immunodeficiency syndrome (AIDS) B. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (positive Hepatitis B surface -Ag (+) or HCV RNA (+) if anti-HCV Ab screening test is positive) 12. If there is a known alcohol or drug abuse 13. In cases of clinically significant (i.e., active) cardiovascular disease: cerebral hemorrhage/brain infarction, myocardial infarction (pre-registration < 6 months), unstable angina, congestive heart failure (NYHA classification ≥2) or arrhythmia needed drug therapy. 14. In case of a mental state in which it is impossible to understand and provide the consent. |
结果
主要结果指标
1. Response rate of treated participants [up to 6 months]
次要成果指标
1. Progression free survival (PFS) duration of treated participants [up to 12 months]
2. Overall survival (OS) duration of treated participants [up to 12 months]
3. Incidence of Treatment-Emergent Adverse Events of participants [up to 12 months]
4. Evaluation of Life quality of participants [up to 12 months]