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

NCT04097028 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: I 443819
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

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.

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Median Progression Free Survival

  Time from treatment until disease progression, death from disease, or last follow-up, assessed up to 2 years

• Median Overall Survival

  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

  Up to 30 days after last dose of study drug, which is a maximum of 210 days.

Study Arms (1)

Treatment (TAS-102, oxaliplatin)

EXPERIMENTAL

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: Trifluridine and Tipiracil Hydrochloride; Drug: Oxaliplatin

Interventions

Trifluridine and Tipiracil Hydrochloride DRUG

Given PO

Also known as: 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

Treatment (TAS-102, oxaliplatin)

Oxaliplatin DRUG

Given IV

Also known as: 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

Treatment (TAS-102, oxaliplatin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• National Comprehensive Cancer Network: collaborator

Study Sites (2)

Roswell Park Cancer Institute

Buffalo, New York, 14203, United States

Location

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

Oklahoma City, Oklahoma, 73104, United States

Location

Related Publications (1)

• 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.

  PMID: 40200573 DERIVED

MeSH Terms

Interventions

Trifluridine; trifluridine tipiracil drug combination; Thymidine; Oxaliplatin

Intervention Hierarchy (Ancestors)

Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: Kris Attwood
• Organization: Roswell Park Comprehensive Cancer Center

Kris.Attwood@roswellpark.org

716-845-2300

Study Officials

• Christos Fountilas, MD

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2019
• First Posted: September 20, 2019
• Study Start: December 20, 2019
• Primary Completion: December 16, 2022
• Study Completion: February 5, 2025
• Last Updated: April 29, 2025
• Results First Posted: January 18, 2024

Record last verified: 2025-03

Locations

US (2)