POF Versus FOLFOX Plus IP Paclitaxel in AGC

A Phase 2 Study of POF(Paclitaxel/Oxaliplatin/5-Fluorouracil/Leucovorin) Versus FOLFOX Plus Intraperitoneal Paclitaxel as a First-line Treatment in Advanced Gastric Cancer With Peritoneal Metastases

The aim of this study was to compare the efficacy and safety of intravenous or intraperitoneal paclitaxel plus FOLFOX as first-line treatment in AGC with peritoneal metastases, a phase II Clinical trial.

Study Overview

• Status: Not yet recruiting
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: POF; Drug: FOLFOX plus PAC(ip)

• Study Type: Interventional
• Enrollment (Anticipated): 260
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18-75 years old;
• Patients must have histologically or cytologically confirmed metastatic or unresectable gastric or gastroesophageal junction (GEJ) adenocarcinoma. GEJ adenocarcinoma may be classified according to Siewert's classification type I, II, or III
• Histological documentation of local recurrence or metastasis is strongly encouraged, unless the risk of such a procedure outweighs the potential benefit of confirming the metastatic disease.
• If no histologic confirmation, then the metastases or recurrence will require documentation by a 2nd radiographic procedure (eg. PET/CT scan or MRI in addition to the CT scan). If the imaging procedure does not confirm recurrent or metastatic disease, biopsy confirmation will be required.
• Patients must have ascites or peritoneal carcinomatosis confirmed by image (CT or MR or US or others) operation.
• Patients may have received no prior chemotherapy for metastatic or unresectable disease. Patients may have received prior adjuvant therapy (chemotherapy and/or chemoradiation) if more than 6 months have elapsed between the end of adjuvant therapy and registration.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1;
• An expected survival of ≥ 3 months;
• Major organ function has to meet the following criteria; (1) For results of blood routine test:
• Hemoglobin (HB) ≥ 80g / L,
• ANC(absolute neutrophil count) ≥ 1.5 × 109 / L,
• PLT(blood platelet) ≥ 75 × 109 / L, (2) For results of biochemical tests:
• BLT（total bilirubin） ≤ 1.25 times the upper limit of normal (ULN),
• ALT(Alanine aminotransferase) and AST(aspartate aminotransferase ) ≤ 2.5 × ·ULN, liver metastases, if any, the ALT and AST≤ 5 × ULN,
• Serum Cr（creatinine）≤1ULN, Endogenous creatinine clearance rate >50ml/min;
• The patient has a PT（prothrombintime） (INR international normalized ratio) < or = to 1.5 and an PTT（Partial Thromboplastin Time）< than or = to 3 seconds above the upper limits of normal if the patientia t is not on anticoagulation. ·If a patient is on full-dose anticoagulants, the following criteria should be met for enrollment:
• The patient must have an in-range INR (usually between 2 and 3) on a stable dose of warfarin or on stable dose of LMW(Low molecular weight) heparin
• The patient must not have active bleeding or pathological conditions that carry high risk of bleeding (e.g. tumor involving major vessels, known varices)
• Pregnancy test (serum or urine) has to be performed for woman of childbearing age within 7 days before enrolment and the test result must be negative.
• Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter.
• Ability to understand informed consent and signing of written informed consent document prior to initiation of protocol therapy.

Exclusion Criteria:

- Patients who have received previous chemotherapy for the treatment of metastatic or unresectable gastric or GEJ adenocarcinoma are ineligible.

• Patients who have received previous pre- or post-operative chemotherapy or chemoradiation are ineligible if therapy was completed less than 6 months prior to study registration. Patients must have recovered from adverse events from any previous therapy.
• Patients with a history of another neoplastic disease within the past three years, excluding basal cell carcinoma of the skin, cervical carcinoma in situ, or nonmetastatic prostate cancer.
• Patients with brain or central nervous system metastases, including leptomeningeal disease.
• Pregnant (positive pregnancy test) or breast feeding.
• Serious, non-healing wound, ulcer, or bone fracture.
• Significant cardiac disease as defined as:

unstable angina, New York Heart Association (NYHA) grade II or greater, congestive heart failure, history of myocardial infarction within 6 months Evidence of bleeding diathesis or coagulopathy.

• History of a stroke or CVA within 6 months
• Clinically significant peripheral vascular disease.
• Inability to comply with study and/or follow-up procedures.
• Patients with any other medical condition or reason, in that investigator's opinion, makes the patient unstable to participate in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: POF; The POF regimen consisted of a 3-hour infusion of paclitaxel (135 mg/m2) followed by oxaliplatin (85 mg/m2) and Calcium Levofolinate (200 mg/m2).Subsequently, a 46-hour infusion of fluorouracil (2400 mg/m2) was administered using an ambulatory pump, repeating the cycle every 14 days. The combined chemotheraphy will be treated for 9 circle. then，the capetabine was allowed	Drug: POF; Paclitaxel plus Oxaliplatin plus Leucovorin plus 5-FU
Experimental: FOLFOX plus PAC(ip); The regimen consisted of oxaliplatin (85 mg/m2) and Calcium Levofolinate (200 mg/m2) plus paclitaxel (80 mg/m2) intra-peritoneally.Subsequently, a 46-hour infusion of fluorouracil (2400 mg/m2) was administered using an ambulatory pump, repeating the cycle every 14 days.	Drug: FOLFOX plus PAC(ip); FOLFOX plus intraperitoneally paclitaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival(OS)	The length of time from enrollment until the time of death	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Event（AE）	Adverse Event according to NCI CTCAE 5 criteria	6month
Objective Overall Response Rate (ORR)	Clinical response of treatment according to RESIST v1.1 criteria	6month

Collaborators and Investigators

• Sponsor: Fujian Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2019
• Primary Completion (Anticipated): November 30, 2022
• Study Completion (Anticipated): June 30, 2023

Study Registration Dates

• First Submitted: October 31, 2019
• First Submitted That Met QC Criteria: November 5, 2019
• First Posted (Actual): November 7, 2019

Study Record Updates

• Last Update Posted (Actual): November 7, 2019
• Last Update Submitted That Met QC Criteria: November 5, 2019
• Last Verified: November 1, 2019

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
• Other Study ID Numbers: FNF-018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No