Clinical trial NCT03606928: mFLOT Chemotherapy as First-line Treatment in GC
Official title: Modified FLOT Chemotherapy as First-line Treatment in Advanced or Metastatic Gastric Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Gastric Cancer
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
First posted: 2018-07-31
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A single center phase 1b/2 trail to identified suitable dosage and its efficacy of modified FLOT regime in Chinese gastric cancer patients. This trial is designed to identified recommended phase II dose (RP2D) of modified FLOT in Chinese patients, and to evaluate the efficacy of modified FLOT regime as first-line for advanced or metastatic gastric cancer.

This trial is in 2 stages: the first stage will establish the maximum tolerated dose (MTD) and RP2D of docetaxel and oxaliplatin in FLOT regime. In the second stage, the efficacy of modified FLOT will be assessed by response rate.

Detailed description: The RP2D of FLOT regime will be established with a standard 3+3 design, starting with the dose of 40mg/m2 docetaxel (dose level 1) and 65mg/m2 oxaliplatin (dose level 1). The plan of dose escalation will be found in following table. Chemotherapy will be administered two-weekly (maximum 12 cycles) until progression of disease, intolerable toxicity or withdraw of patients.

Eligibility criteria: Inclusion Criteria:

1. Male/female patients aged from 18 to 75 years.
2. Histologically confirmed gastric adenocarcinoma.
3. Gastric tumors should be treatment naïve unresectable or metastatic disease, or recurrence over 6 months after finish of adjuvant chemotherapy.
4. At least one measurable lesion should be confirmed by imaging examination.
5. ECOG performance status 0 or 1
6. Adequate bone marrow function:

   Absolute neutrophil count (ANC) ≥1.5x109/L White blood count ≥3.5x109/L Platelets ≥80x109/L Hemoglobin (Hb) ≥90g/L (can be post-transfusion)
7. Adequate renal function: Creatinine Clearance of \>50ml/min
8. Adequate liver function:

Serum bilirubin \<22 umol/L ALT/AST ≤2.5x ULN, for patient with liver metastasis ALT/AST ≤5x ULN 10. Adequate coagulation profile International Normalised Ratio (INR) \< 1.5 Activated Prothrombin Time (APTT) \< 1.5xULN 11. Without brain metastasis and peripheral nerve diseases 12. Willingness and ability to comply with the protocol for the duration of the study including scheduled visits, examinations, investigations and treatment plans with informed consent form.

Exclusion Criteria:

1. With second primary malignant diseases
2. Any contraindication or known hypersensitivity reaction to any of the study drugs, or components of leucovorin, oxaliplatin, 5-FU or docetaxel
3. With uncontrollable complications
4. Inadequate organ function
5. Pregnancy or of child bearing potential.

Primary outcomes:
measure: Maximum tolerated dose and recommended phase II dose of modified FLOT regime
timeFrame: 36 months
measure: Objective response rate
timeFrame: 36 months
Secondary outcomes:
measure: Overall survival
timeFrame: 36 months
measure: Progression free survival
timeFrame: 36 months
measure: Safety: adverse events as assessed by CTCAE v4.0
timeFrame: 36 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Department of Oncology, Ruijin Hospital
Study officials:
affiliation: Ruijin Hospital
name: Jun Zhang, MD & Ph. D
role: PRINCIPAL_INVESTIGATOR
References: