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

Primary Purpose

Clinical Stage IIA Esophageal Adenocarcinoma AJCC v8, Clinical Stage IIA Gastroesophageal Junction Adenocarcinoma AJCC v8, Clinical Stage III Esophageal Adenocarcinoma AJCC v8

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Trifluridine and Tipiracil Hydrochloride
Oxaliplatin
Sponsored by
Roswell Park Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Clinical Stage IIA Esophageal Adenocarcinoma AJCC v8

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Roswell Park Cancer Institute
  • Stephenson Oklahoma Cancer Center at the University of Oklahoma Health Science Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (TAS-102, oxaliplatin)

Arm Description

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.

Outcomes

Primary Outcome Measures

Pathologic complete response rate
Will be determined by pathologic examination of resected specimen: complete and partial 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.

Secondary Outcome Measures

Progression free survival rate
Will be summarized using standard Kaplan-Meier methods; where estimates of median survival and two-year survival rates will be obtained with 90% confidence intervals.
Overall survival
Will be summarized using standard Kaplan-Meier methods; where estimates of median survival and two-year survival rates will be obtained with 90% confidence intervals
Incidence of 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.

Full Information

First Posted
September 18, 2019
Last Updated
August 9, 2023
Sponsor
Roswell Park Cancer Institute
Collaborators
National Comprehensive Cancer Network
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1. Study Identification

Unique Protocol Identification Number
NCT04097028
Brief Title
Use of Trifluridine/Tipiracil and Oxaliplatin as Induction Chemotherapy for the Treatment of Resectable Esophageal or Gastroesophageal Junction (GEJ) Adenocarcinoma
Official Title
Use of Trifluridine/Tipiracil (TAS-102) and Oxaliplatin as Induction Chemotherapy in Resectable Esophageal and Gastroesophageal Junction (GEJ) Adenocarcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 20, 2019 (Actual)
Primary Completion Date
December 16, 2022 (Actual)
Study Completion Date
December 16, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Roswell Park Cancer Institute
Collaborators
National Comprehensive Cancer Network

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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 for years 3-5, and then annually thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
22 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (TAS-102, oxaliplatin)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Trifluridine and Tipiracil Hydrochloride
Other Intervention Name(s)
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
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Other Intervention Name(s)
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
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Pathologic complete response rate
Description
Will be determined by pathologic examination of resected specimen: complete and partial 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.
Time Frame
Up to 5 years
Secondary Outcome Measure Information:
Title
Progression free survival rate
Description
Will be summarized using standard Kaplan-Meier methods; where estimates of median survival and two-year survival rates will be obtained with 90% confidence intervals.
Time Frame
Time from treatment until disease progression, death from disease, or last follow-up, assessed up to 2 years
Title
Overall survival
Description
Will be summarized using standard Kaplan-Meier methods; where estimates of median survival and two-year survival rates will be obtained with 90% confidence intervals
Time Frame
Time from treatment until death due to any cause or last follow-up, assessed up to 2 years
Title
Incidence of adverse events
Description
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.
Time Frame
Up to 30 days after last dose of study drug

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sarbjit Mukherjee, MD
Organizational Affiliation
Roswell Park Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14203
Country
United States
Facility Name
Stephenson Oklahoma Cancer Center at the University of Oklahoma Health Science Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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