A Randomized, Open Labeled Phase II Pilot Study of Total Neoadjuvant Chemotherapy With FLOT ( FLOT-TNT) VS Standard Perioperative FLOT ( FLOTPOP) in Patients With Gastric or GEJ Cancer, and Assessment of CTDNA as Correlative Biological Response
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 5
- 主要终点
- Completion Rate of Participants Who Have Completed Their All-allocated Treatments, Either Arm A: FLOT-TNT or Arm B: FLOT-POP
研究概览
简要总结
This is a randomized pilot study to evaluate and to compare the completion rates of Total Neoadjuvant chemotherapy with FLOT ( FLOT-TNT) and perioperative chemotherapy with FLOT ( FLOT-POP).
详细描述
Participants will be randomized 1:1 to either total Neoadjuvant chemotherapy with with FLOT-TNT ( all 4 cycles of chemotherapy before surgery) or standard of care FLOT-POP ( 2 cycles of chemotherapy before surgery and 2 cycles of chemotherapy after surgery). Each cycle of chemo is 28 days long with chemo administered on Days 1 and Day 15 of the cycle.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must provide written informed consent.
- •Must be ≥18 years of age.
- •Must have life expectancy of greater than 3 months.
- •Must have pathologically proven Siewert type II or III GEJ or gastric adenocarcinoma from the main tumor or local lymph nodes (pre-neoadjuvant chemo).
- •Stage cT2 or higher, any N and M0, are eligible for the study.
- •M0 disease must be established by both negative distant metastatic disease on imaging AND negative diagnostic laparoscopic assisted cytology of peritoneal fluid cytology not more than 42 days before registration.
- •Must be a candidate for neoadjuvant chemotherapy.
- •Must be a candidate for curative surgical approach.
- •Must have an ECOG performance status 0-
- •Male or female subjects of childbearing potential must be willing to use contraceptive precautions throughout the trial and for 3 months after discontinuation of study treatment. Female subjects of childbearing potential must have a negative pregnancy test within 28 days of registration. Post-menopausal women must be amenorrhoeic for at least 12 months to be considered of non-childbearing potential.
- •Must have adequate kidney, liver, and bone marrow function, within 28 days prior to registration, as follows:
- •i. Hemoglobin ≥ 8.0 gm/dL (PRBC transfusion is allowed to meet this criteria) ii. Absolute neutrophil count (ANC) ≥ 1000 cells/mm3 iii. Platelet count ≥ 100,000 /mm3 iv. Total bilirubin ≤ 1.5 times upper limit of normal (ULN) v. AST (SGOT) and ALT (SGPT) ≤ 3.0 times the ULN vi. Patient must have adequate renal function as evidenced by one of the following: Serum creatinine ≤ IULN OR calculated creatinine clearance ≥ 60 mL/min. This serum creatinine result must be obtained within 28 days prior to registration.
- •l. Subjects who have required a short course urgent single modality non curative radiation treatment or gastric artery embolization for the purpose of tumor bleeding control are eligible.
排除标准
- •Positive cytology or histology for metastatic disease on diagnostic laparoscopy peritoneal fluid. Reports such as: "cannot rule out malignancy" or "suspicious for malignancy, but not definitive" will exclude the subject from enrolling.
- •Seiwert type I GEJ cancer
- •Subjects with clinical evidence of metastatic disease.
- •Biopsy proven metastatic disease (excluding regional lymph nodes)
- •Prior chemotherapy for gastric cancer or GEJ cancer
- •No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, current non-advanced prostate cancer per the discretion of the investigator, and any other cancers from which the patient has been disease free for two years.
- •Female subjects who are pregnant, breast feeding, or of childbearing potential with a positive pregnancy test prior to baseline. Women of childbearing potential must have a negative serum pregnancy test as a part of eligibility within 28 days of registration. A persistent positive or elevated urine or blood Beta HCG test may be contributed to the primary diagnosis of GC or GEJ cancer after ruling out ectopic and intrauterine pregnancy and germ cell tumors.
- •Subjects unwilling or unable to comply with the protocol or provide written informed consent.
- •Any medical condition that, in the opinion of the investigator, would exclude the subject from participating in this study and treatment plan.
研究组 & 干预措施
Arm A: FLOT-TNT ( Investigational Arm)
Arm A is the investigational arm with all 4 cycles of FLOT given as total neoadjuvant chemotherapy prior to surgery. Each cycle is 28 days and consists of 2 chemotherapy sessions given every 14 days. The total number of chemotherapy sessions in Arm A is 8. Every effort will be made to have surgery in week 20 ( -1 to +2 weeks), 4 weeks post C4 on arm A.
干预措施: Oxaliplatin (Drug)
Arm A: FLOT-TNT ( Investigational Arm)
Arm A is the investigational arm with all 4 cycles of FLOT given as total neoadjuvant chemotherapy prior to surgery. Each cycle is 28 days and consists of 2 chemotherapy sessions given every 14 days. The total number of chemotherapy sessions in Arm A is 8. Every effort will be made to have surgery in week 20 ( -1 to +2 weeks), 4 weeks post C4 on arm A.
干预措施: GSCF (Biological)
Arm B: FLOT-POP ( Standard Arm)
Arm B us the standard perioperative arm with 2 cycles of pre-operative FLOT ( 4 treatment sessions) and 2 cycles ( 4 treatment sessions) of post-operative FLOT. Post-surgery FLOT will start 4-6 weeks post surgery. Each cycle of chemotherapy consists of 28 days and consists of 2 chemotherapy sessions given every 14 days. The total number of chemotherapy sessions in arm B is 8. Every effort should be done to have surgery done in week 12 ( -1 to +2 weeks) post completion of cycle 2 on ARM B.
干预措施: GSCF (Biological)
Arm A: FLOT-TNT ( Investigational Arm)
Arm A is the investigational arm with all 4 cycles of FLOT given as total neoadjuvant chemotherapy prior to surgery. Each cycle is 28 days and consists of 2 chemotherapy sessions given every 14 days. The total number of chemotherapy sessions in Arm A is 8. Every effort will be made to have surgery in week 20 ( -1 to +2 weeks), 4 weeks post C4 on arm A.
干预措施: Fluorouracil (Drug)
Arm A: FLOT-TNT ( Investigational Arm)
Arm A is the investigational arm with all 4 cycles of FLOT given as total neoadjuvant chemotherapy prior to surgery. Each cycle is 28 days and consists of 2 chemotherapy sessions given every 14 days. The total number of chemotherapy sessions in Arm A is 8. Every effort will be made to have surgery in week 20 ( -1 to +2 weeks), 4 weeks post C4 on arm A.
干预措施: Leucovorin (Drug)
Arm A: FLOT-TNT ( Investigational Arm)
Arm A is the investigational arm with all 4 cycles of FLOT given as total neoadjuvant chemotherapy prior to surgery. Each cycle is 28 days and consists of 2 chemotherapy sessions given every 14 days. The total number of chemotherapy sessions in Arm A is 8. Every effort will be made to have surgery in week 20 ( -1 to +2 weeks), 4 weeks post C4 on arm A.
干预措施: Docetaxel (Drug)
Arm B: FLOT-POP ( Standard Arm)
Arm B us the standard perioperative arm with 2 cycles of pre-operative FLOT ( 4 treatment sessions) and 2 cycles ( 4 treatment sessions) of post-operative FLOT. Post-surgery FLOT will start 4-6 weeks post surgery. Each cycle of chemotherapy consists of 28 days and consists of 2 chemotherapy sessions given every 14 days. The total number of chemotherapy sessions in arm B is 8. Every effort should be done to have surgery done in week 12 ( -1 to +2 weeks) post completion of cycle 2 on ARM B.
干预措施: Leucovorin (Drug)
Arm B: FLOT-POP ( Standard Arm)
Arm B us the standard perioperative arm with 2 cycles of pre-operative FLOT ( 4 treatment sessions) and 2 cycles ( 4 treatment sessions) of post-operative FLOT. Post-surgery FLOT will start 4-6 weeks post surgery. Each cycle of chemotherapy consists of 28 days and consists of 2 chemotherapy sessions given every 14 days. The total number of chemotherapy sessions in arm B is 8. Every effort should be done to have surgery done in week 12 ( -1 to +2 weeks) post completion of cycle 2 on ARM B.
干预措施: Docetaxel (Drug)
Arm B: FLOT-POP ( Standard Arm)
Arm B us the standard perioperative arm with 2 cycles of pre-operative FLOT ( 4 treatment sessions) and 2 cycles ( 4 treatment sessions) of post-operative FLOT. Post-surgery FLOT will start 4-6 weeks post surgery. Each cycle of chemotherapy consists of 28 days and consists of 2 chemotherapy sessions given every 14 days. The total number of chemotherapy sessions in arm B is 8. Every effort should be done to have surgery done in week 12 ( -1 to +2 weeks) post completion of cycle 2 on ARM B.
干预措施: Fluorouracil (Drug)
Arm B: FLOT-POP ( Standard Arm)
Arm B us the standard perioperative arm with 2 cycles of pre-operative FLOT ( 4 treatment sessions) and 2 cycles ( 4 treatment sessions) of post-operative FLOT. Post-surgery FLOT will start 4-6 weeks post surgery. Each cycle of chemotherapy consists of 28 days and consists of 2 chemotherapy sessions given every 14 days. The total number of chemotherapy sessions in arm B is 8. Every effort should be done to have surgery done in week 12 ( -1 to +2 weeks) post completion of cycle 2 on ARM B.
干预措施: Oxaliplatin (Drug)
结局指标
主要结局
Completion Rate of Participants Who Have Completed Their All-allocated Treatments, Either Arm A: FLOT-TNT or Arm B: FLOT-POP
时间窗: at week 16 for Arm A and at week 24 for Arm B
ArmA has all 4 cycles of FLOT given prior to surgery and ArmB has 2 cycles of pre-operative FLOT and 2 cycles of post-operative FLOT. Each cycle consists of 28 days and consists of 2 chemotherapy sessions given every 14 days. The completion rate of participants is presented based on the number of participants who have completed all treatments by their arms.
次要结局
- Rate of Pathologic Nodal Stage (ypN1-ypN3)(at week 12 for Arm A and at week 20 for Arm B)
- Pathologic Response Rate(at week 12 for Arm A and at week 20 for Arm B)
- Number of Positive Lymph Nodes(at week 12 for Arm A and at week 20 for Arm B)
研究者
Tannaz Armaghnay
Assistant Professor
Baylor College of Medicine