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

Use of Trifluridine/Tipiracil (TAS-102) and Oxaliplatin as Induction Chemotherapy in Resectable Esophageal and Gastroesophageal Junction (GEJ) Adenocarcinoma

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IIA Esophageal Adenocarcinoma AJCC v8; Clinical Stage III Esophageal Adenocarcinoma AJCC v8; Clinical Stage IVA Esophageal Adenocarcinoma AJCC v8; Pathologic Stage IIB Esophageal Adenocarcinoma AJCC v8; Pathologic Stage III Esophageal Adenocarcinoma AJCC v8; Pathologic Stage IIIA Esophageal Adenocarcinoma AJCC v8; Pathologic Stage IIIB Esophageal Adenocarcinoma AJCC v8; Pathologic Stage IVA Esophageal Adenocarcinoma AJCC v8; Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IIA Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIB Gastroesophageal Junction Adenocarcinoma AJCC v8
• Intervention / Treatment: Drug: Oxaliplatin; Drug: Trifluridine and Tipiracil Hydrochloride

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 for years 3-5, and then annually thereafter.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14203
      • Roswell Park Cancer Institute
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Stephenson Oklahoma Cancer Center at the University of Oklahoma Health Science Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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: 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.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With a Pathologic Complete Response	Will be determined by pathologic examination of resected specimen: complete response to induction chemotherapy followed by standard chemoradiation and surgery. Will be summarized using frequencies and relative frequencies. Will be estimated using an 80% confidence interval obtained using Jeffrey's prior method. Response is assessed by the tumor regression score (as proposed by NCCN guidelines): Complete Response: No viable cancer cells, including lymph nodes Near Complete Response: Single cells or rare small groups of cancer cells Partial Response: Residual cancer with evident tumor regression but more than single cells or rare small groups of cancer cells Poor or No Response: Extensive residual disease with no evident tumor regression	Assessed at the time of surgery (approximately 6 months after start of neoadjuvant therapy)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Progression Free Survival	Will be summarized using standard Kaplan-Meier methods; where estimates of median survival and two-year survival rates will be obtained with 95% confidence intervals. Progression is assessed by RECIST v1.0, defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	Time from treatment until disease progression, death from disease, or last follow-up, assessed up to 2 years
Median Overall Survival	Will be summarized using standard Kaplan-Meier methods; where estimates of median survival and two-year survival rates will be obtained with 95% confidence intervals	Time from treatment until death due to any cause or last follow-up, assessed up to 2 years
Number of Patients With Grade 3 or Higher Treatment Related Adverse Events	Toxicities and adverse events (as per Common Terminology Criteria for Adverse Events version 5.0) will be summarized by attribution and grade using frequencies and relative frequencies.	Up to 30 days after last dose of study drug, which is a maximum of 210 days.

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Collaborators: National Comprehensive Cancer Network
• Investigators: Principal Investigator: Sarbjit Mukherjee, MD, Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2019
• Primary Completion (Actual): December 16, 2022
• Study Completion (Estimated): December 16, 2024

Study Registration Dates

• First Submitted: September 18, 2019
• First Submitted That Met QC Criteria: September 19, 2019
• First Posted (Actual): September 20, 2019

Study Record Updates

• Last Update Posted (Actual): January 18, 2024
• Last Update Submitted That Met QC Criteria: December 21, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Adenocarcinoma; Esophageal Neoplasms; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Antineoplastic Agents; Oxaliplatin; Trifluridine
• Other Study ID Numbers: I 443819

Drug and device information, study documents

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