Use of Trifluridine/Tipiracil and Oxaliplatin as Induction Chemotherapy for the Treatment of Resectable Esophageal or Gastroesophageal Junction (GEJ) Adenocarcinoma

NCT ID: NCT04097028

Last Updated: 2025-04-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-20
• Study Completion Date: 2025-02-05

Brief Summary

This phase II trial studies how well trifluridine/tipiracil and oxaliplatin work as the first line of treatment (induction) in treating patients with esophageal or gastroesophageal junction adenocarcinoma that can be removed by surgery (resectable). Drugs used in chemotherapy, such as trifluridine/tipiracil and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Detailed Description

PRIMARY OBJECTIVE:

-Evaluate the pathologic complete response (path CR) rate in participants with esophageal and gastroesophageal junction (GEJ) adenocarcinoma when trifluridine and tipiracil hydrochloride (trifluridine/tipiracil [TAS-102]) and oxaliplatin are used as induction chemotherapy prior to surgical resection.

SECONDARY OBJECTIVES:

• Evaluate the 2-year disease-free survival (DFS) and the 2-year overall survival (OS)
• To determinate the safety and tolerability of induction chemotherapy with trifluridine/tipiracil (TAS 102) and oxaliplatin followed by standard chemoradiation and surgery
• Evaluate the metabolic response to induction chemotherapy with TAS 102 and oxaliplatin in participants with esophageal and gastroesophageal junction (GEJ) adenocarcinoma prior to standard chemoradiation and surgical resection

EXPLORATORY OBJECTIVE:

-Correlate circulating tumor deoxyribonucleic acid (DNA) levels with disease recurrence and metabolic response on positron emission tomography (PET) computed tomography (CT).

OUTLINE:

Patients receive oxaliplatin intravenously (IV) over 2 hours on day 1 and trifluridine and tipiracil hydrochloride orally (PO) twice daily (BID) on days 1-5. Treatment repeats every 14 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care chemoradiation therapy followed by surgery.

After completion of study treatment, patients are followed up every 3-6 months for years 1-2, every 6-12 months.

Conditions

Clinical Stage IIA Esophageal Adenocarcinoma AJCC v8; Clinical Stage IIA Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage III Esophageal Adenocarcinoma AJCC v8; Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IVA Esophageal Adenocarcinoma AJCC v8; Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIB Esophageal Adenocarcinoma AJCC v8; Pathologic Stage IIB Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage III Esophageal Adenocarcinoma AJCC v8; Pathologic Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIIA Esophageal Adenocarcinoma AJCC v8; Pathologic Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIIB Esophageal Adenocarcinoma AJCC v8; Pathologic Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IVA Esophageal Adenocarcinoma AJCC v8; Pathologic Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (TAS-102, oxaliplatin)

Patients receive oxaliplatin IV over 2 hours on day 1 and trifluridine and tipiracil hydrochloride PO BID on days 1-5. Treatment repeats every 14 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care chemoradiation therapy followed by surgery.

Group Type: EXPERIMENTAL

Trifluridine and Tipiracil Hydrochloride

Intervention Type: DRUG

Given PO

Oxaliplatin

Intervention Type: DRUG

Given IV

Interventions

Trifluridine and Tipiracil Hydrochloride

Given PO

Intervention Type: DRUG

Oxaliplatin

Given IV

Intervention Type: DRUG

Other Intervention Names

733030-01-8; Lonsurf; TAS 102; Thymidine; Mixt. with 5-Chloro-6-((2-imino-1-pyrrolidinyl)methyl)-2,4(1H,3H)-pyrimidinedione Monohydrochloride; Tipiracil Hydrochloride Mixture with Trifluridine; Trifluridine/Tipiracil; 1-OHP; 266046; 61825-94-3; [(1R,-2R)-1,2-cyclohexanediamine-N,N''][oxalato (2--)-O,O'']platinum; Ai Heng; Aiheng; Dacotin; Dacplat; Diaminocyclohexane Oxalatoplatinum; Eloxatin; Eloxatine; JM-83; oxalato (1R,2R-cyclohexanediamine)platinum(II); oxalato (trans-l-1,2-diaminocyclohexane)platinum(II); Oxalatoplatin; OXALIPLATIN,; RP 54780; RP-54780; SR-96669; trans-l DACH oxalatoplatinum

Eligibility Criteria

Inclusion Criteria

• Must have histologically proven loco-regional esophageal or gastroesophageal junction adenocarcinoma
• Endoscopic ultrasound (EUS), or clinically determined node-positive disease with any T-stage or T3-T4a with any N stage: Patients with EUS T4b and any M1 cancer will not be included
• Must have potentially resectable disease
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Hemoglobin >= 9 g/dL
• Absolute neutrophil count >= 1500/mm^3
• Platelet count >= 100,000/mm^3
• Creatinine < 1.5 upper limit of normal (ULN)
• Bilirubin < 1.5 x ULN
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x ULN
• Capacity to take oral tablet(s) without difficulty
• Participants of child-bearing potential must agree to use highly effective contraceptive methods (e.g., hormonal plus barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria

• Prior chemotherapy, thoracic radiotherapy or prior surgical resection for an esophageal tumor
• Participants with known metastatic disease
• Any concurrent active malignancy that requires active systemic intervention
• Grade 2 or higher peripheral neuropathy
• Participants who have had major surgery or field radiation within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Received an investigational agent within 4 weeks prior to enrollment
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Grade 3 or higher hypersensitivity reaction to oxaliplatin or grade 1-2 hypersensitivity reaction to oxaliplatin not controlled with premedication
• Patient previously treated by TAS 102 or history of allergic reactions attributed to compounds of similar composition to TAS 102 or any of its excipients
• Hereditary problems of galactose intolerance; e.g., Lapp lactase deficiency or glucose galactose malabsorption
• Pregnant or nursing female participants
• Unwilling or unable to follow protocol requirements
• Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Comprehensive Cancer Network

NETWORK

Sponsor Role: collaborator

Roswell Park Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christos Fountilas, MD

Role: PRINCIPAL_INVESTIGATOR

Roswell Park Cancer Institute

Locations

Roswell Park Cancer Institute

Buffalo, New York, United States

Stephenson Oklahoma Cancer Center at the University of Oklahoma Health Science Center

Oklahoma City, Oklahoma, United States

Countries

United States

References

Mukherjee S, Fujiwara Y, Fountzilas C, Pattnaik H, Chatley S, Vadehra D, Kukar M, Attwood K, George A, Advani S, Yu H, Catalfamo K, Brown A, Spickard E, Fungtammasan A, George S, Liao CY, Iyer R, Hatoum H. Trifluridine/Tipiracil and Oxaliplatin as Induction Chemotherapy in Resectable Esophageal and Gastroesophageal Junction Adenocarcinoma: A Phase II Study. Cancer Med. 2025 Apr;14(7):e70835. doi: 10.1002/cam4.70835.

Reference Type: DERIVED

PMID: 40200573 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

I 443819

Identifier Type: -

Identifier Source: org_study_id