mFLOT Chemotherapy as First-line Treatment in GC

Modified FLOT Chemotherapy as First-line Treatment in Advanced or Metastatic Gastric Cancer

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.

Study Overview

• Status: Completed
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: docetaxel, oxaliplatin, 5-FU, leucovorin

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200025
    • Department of Oncology, Ruijin Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: modified FLOT; modified FLOT Docetaxel 40mg/m2 ivgtt day 1 over 1 hour Oxaliplatin 65mg/m2 ivgtt day 1 over 2hours Dose escalation will be performed. Leucovorin 200mg/m2 ivgtt day 1 over 2 hours 5-FU 2200mg/m2 civ over 24 hours	Drug: docetaxel, oxaliplatin, 5-FU, leucovorin; This is a single-arm study with all patients receiving mFLOT chemotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum tolerated dose and recommended phase II dose of modified FLOT regime	36 months
Objective response rate	36 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	36 months
Progression free survival	36 months
Safety: adverse events as assessed by CTCAE v4.0	36 months

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2018
• Primary Completion (Actual): November 9, 2019
• Study Completion (Actual): January 1, 2020

Study Registration Dates

• First Submitted: July 22, 2018
• First Submitted That Met QC Criteria: July 28, 2018
• First Posted (Actual): July 31, 2018

Study Record Updates

• Last Update Posted (Actual): March 20, 2020
• Last Update Submitted That Met QC Criteria: March 18, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protective Agents; Micronutrients; Vitamins; Antidotes; Vitamin B Complex; Docetaxel; Oxaliplatin; Leucovorin
• Other Study ID Numbers: mFLOT-GC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: We have no plan to make individual participant data (IPD) available to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No