Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma
Conditions
Keywords
Gastric cancer, GEJ cancer
Brief summary
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).
Detailed description
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.
Interventions
DRUGFluorouracil
2600 mg/m2 IV over 26 hours (+/-1 hour) CI with home pump Day 1,15
DRUGLeucovorin
200 mg mg/m2 IV over 2 hours Day 1,15
DRUGOxaliplatin
85 mg/m2 IV over 2 hours Day 1,15
DRUGDocetaxel
60 mg/m2 IV over 60 minutes Day 1,15
BIOLOGICALGSCF
Recommended on day 2 and 16 of C1 of the protocol while getting chemotherapy Day 2,16
Sponsors
Baylor College of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This study is a two arm phase II pilot design, with eligible subjects randomized 1:1 to either Arm A ( Investigational arm) or Arm B ( Standard arm). The chemotherapy dose modification will follow routine clinical care. Both arms will receive chemotherapy and curative surgery.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Must provide written informed consent. 2. Must be ≥18 years of age. 3. Must have life expectancy of greater than 3 months. 4. Must have pathologically proven Siewert type II or III GEJ or gastric adenocarcinoma from the main tumor or local lymph nodes (pre-neoadjuvant chemo). 5. Stage cT2 or higher, any N and M0, are eligible for the study. 6. 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. 7. Must be a candidate for neoadjuvant chemotherapy. 8. Must be a candidate for curative surgical approach. 9. Must have an ECOG performance status 0-2. 10. 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. 11. 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.
Exclusion criteria
1. 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. 2. Seiwert type I GEJ cancer 3. Subjects with clinical evidence of metastatic disease. 4. Biopsy proven metastatic disease (excluding regional lymph nodes) 5. Prior chemotherapy for gastric cancer or GEJ cancer 6. 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. 7. 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. 8. Subjects unwilling or unable to comply with the protocol or provide written informed consent. 9. Any medical condition that, in the opinion of the investigator, would exclude the subject from participating in this study and treatment plan. 10. ECOG \> 2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Completion Rate of Participants Who Have Completed Their All-allocated Treatments, Either Arm A: FLOT-TNT or Arm B: FLOT-POP | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Response Rate | at week 12 for Arm A and at week 20 for Arm B | The pathological response will be evaluated by using Mandard tumor regression grade (TRG) in the primary tumor. Mandard TRG score is from TRG0 (complete response), TRG1 (near-complete response), TRG2 (partial response), and TRG3 (poor or no response). |
| Rate of Pathologic Nodal Stage (ypN1-ypN3) | at week 12 for Arm A and at week 20 for Arm B | Pathologic nodal stage is assessed post gastrectomy surgery and an ordinal variable. Nodal status is assessed as positive or negative on pathology. The number of positive lymph nodes is obtained from post gastrectomy surgical specimens. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORTannaz Armaghany, MD
Baylor College of Medicine
Participant flow
Pre-assignment details
Since activation, 3 subjects were enrolled but were not able to be randomized to a treatment arm because of a positive diagnostic laparoscopy result. Given the lack of accrual the study was closed
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
None listed