Clinical trial NCT05567835: A Study of Total Neoadjuvant Chemotherapy With FLOT VS Standard Perioperative FLOT in Patients With Gastric or GEJ Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Gastric Adenocarcinoma
Gastroesophageal Junction Adenocarcinoma
Keywords: Gastric cancer
GEJ cancer
Lead sponsor: Baylor College of Medicine
Sponsor class: OTHER
First posted: 2022-10-05
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Completion rate of Participants who have completed their all-allocated treatments, either Arm A: FLOT-TNT or Arm B: FLOT-POP
timeFrame: at week 16 for Arm A and at week 24 for Arm B
Secondary outcomes:
measure: Pathologic response rate
timeFrame: at week 12 for Arm A and at week 20 for Arm B
measure: Number of positive lymph nodes
timeFrame: at week 12 for Arm A and at week 20 for Arm B
Other outcomes:
Locations:
city: Houston
country: United States
facility: Baylor College of Medicine Medical Center - McNair Campus
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Baylor St. Luke's Medical Center
state: Texas
city: Houston
country: United States
facility: Ben Taub Hospital
state: Texas
city: Houston
country: United States
facility: Harris Health System- Smith Clinic
state: Texas
Study officials:
affiliation: Baylor College of Medicine
name: Tannaz Armaghany, MD
role: PRINCIPAL_INVESTIGATOR
References: