sFOLFOXIRI in Advanced Gastroesophageal Cancer, (SAGE)

Gastro-Intestinal Cancer Clinical Trial

Official title:

A Phase II Study of sFOLFOXIRI in Advanced Gastroesophageal Cancer (SAGE)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05332002
• Other study ID #: 072204
• Secondary ID: Pro2022000268
• Status: Recruiting
• Phase: Phase 2
• Start date: July 13, 2022
• Est. completion date: August 1, 2025

Study information

• Verified date: August 2023
• Source: Rutgers, The State University of New Jersey
• Contact: Patrick Boland, MD
• Phone: (732)235-2465
• Email: pb564[@]cinj.rutgers.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective is to determine the clinical efficacy of treatment regimen in terms of objective response rate (ORR). The secondary objectives is to determine the clinical efficacy of the study treatment in terms of progression free survival (PFS) and overall survival (OS). Additionally, to characterize the safety and toxicity profile of the study treatment as measured by the adverse event rates.

Description:

The overall purpose of this protocol is to serve as a Single Arm Phase II trial of a four week alternating FOLFOX and FOLFIRI (sFOLFOXIRI), with or without nivolumab, in advanced human epidermal growth factor receptor two (HER2) negative gastric and esophageal cancers (GEC). This study evaluates the hypothesis that the use of sFOLFOXIRI in gastroesophageal cancer (GEC) will increase response rates beyond that expected with FOLFOX, while maintaining acceptable tolerability. The primary endpoint of this study is the objective response rate (ORR) while the key secondary endpoints include the progression free survival (PFS), overall survival (OS), and adverse event (AE) rates. The goal of this study is to establish the activity level of sFOLFOXIRI, with the thought that this could be further developed in the metastatic and/or peri-operative space if a sufficiently interesting degree of efficacy is observed.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 38
• Est. completion date: August 1, 2025
• Est. primary completion date: August 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically and/or cytologically confirmed metastatic or unresectable adenocarcinoma of esophageal, gastroesophageal junction or gastric origin

• Tumor is HER2 negative by standard local testing methodology

• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 - 2

• Measurable disease by response evaluation criteria in solid tumors (RECIST) v1.1

• No prior systemic therapy for the present cancer given in the metastatic setting and > 6 months from administration of peri-operative chemotherapy, if applicable

o Note: up to two prior cycles of mFOLFOX6 for the present illness is permitted if patients otherwise qualify for the study with adequate baseline imaging

• At least 18 years of age

• Adequate bone marrow and organ functions as defined by:

• Absolute neutrophil count = 1500 cells/ µL

• Hemoglobin = 8 g/ dL

• Platelets > 100,000 / µL

• Creatinine = 1.5 x upper limit of normal (ULN) OR creatinine clearance = 30 mL/min by Cockroft-Gault

• Total bilirubin = ULN

• Aspartate aminotransferase (AST)/ Alanine aminotransferase (ALT) < 2.5 x ULN, unless with liver metastases and then must be <5 x ULN of normal

• Women and men of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect pregnancy on study, she must notify her treating physician immediately.

• Ability to understand the nature of this study protocol and give written informed consent.

• Willingness and ability to comply with scheduled visits, treatment plans laboratory tests and other study procedures.

Exclusion Criteria:

• Receipt of any investigational agents at the time of registration

• Known, untreated brain metastases

• Grade two or greater peripheral neuropathy

• Presence of any additional active malignancy within the past three years where the malignancy is at least reasonably likely to later the course of therapy, require systemic therapy or interfere with imaging assessments

• For those patients who are going to receive nivolumab

• No active use of systemic corticosteroids at the time of enrollment, at a dose equivalent of 10 mg/day or prednisone

• Clinically significant autoimmune disease which is active or has required systemic immunosuppression within the last two years

• Prior organ transplant or bone marrow transplant

• History of interstitial lung disease or pneumonitis

• Uncontrolled intercurrent illness, including significant active infection, symptomatic congestive heart failure, unstable angina or active arrhythmia

• Major surgery within the four weeks prior to initiation of study treatment

• A history of allergy or hypersensitivity to any of the study drugs

• Any additional significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from fully participating in the study

Related Conditions & MeSH terms

• Gastro-Intestinal Cancer
• Gastrointestinal Neoplasms
• Intestinal Neoplasms

Intervention

Drug:
• Four week alternating FOLFOX and FOLFIRI (sFOLFOXIRI)
This is a Single Arm Phase II trial of q4week alternating FOLFOX and FOLFIRI (sFOLFOXIRI), with or without nivolumab, in advanced human epidermal growth factor receptor 2 (HER2) negative gastric and esophageal cancers (GEC). The study treatment is a chemotherapy combination of either FOLFOX or FOLFIRI as below: mFOLFOX6: (Oxaliplatin 85 mg/m2 IV, leucovorin 400 mg/m2, 5-FU 400 mg/m2 bolus, then 5-FU 2400 mg/m2: FOLFIRI: (Irinotecan 180 mg/m2 IV, leucovorin 400 mg/m2, 5-FU 400 mg/m2 bolus, then 5-FU 2400 mg/m2 Nivolumab(Optional) The chemotherapy combination of FOLFOX and FOLFIRI is a FDA approved treatment for advanced bowel and gastric

Locations

Country	Name	City	State
United States	RWJBarnabas Health - Robert Wood Johnson University Hospital	Hamilton	New Jersey
United States	RWJBarnabas Health - Monmouth Medical Center Southern Campus	Lakewood	New Jersey
United States	RWJBarnabas Health - Monmouth Medical Center	Long Branch	New Jersey
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	RWJBarnabas Health - Robert Wood Johnson University Hospital, Somerset	New Brunswick	New Jersey
United States	RWJBarnabas Health - Newark Beth Israel Medical Center	Newark	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Rutgers, The State University of New Jersey

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors ( RECIST) criteria version 1.1	To determine the clinical efficacy of treatment regimen in terms of objective response rate.	Three Years
Primary	Progression Free Survival (PFS)	To determine the clinical efficacy of the study treatment in terms of progressive free survival.	Three Years
Primary	Overall Survival (OS)	To determine the clinical efficacy of the study treatment in terms of overall survival.	Three Years
Primary	Adverse Event Rates		Three Years