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

Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04097028
• Other study ID #: I 443819
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 20, 2019
• Est. completion date: December 16, 2024

Study information

• Verified date: November 2023
• Source: Roswell Park Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 22
• Est. completion date: December 16, 2024
• Est. primary completion date: December 16, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• 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
• Esophageal Neoplasms
• 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

Intervention

Drug:
• Trifluridine and Tipiracil Hydrochloride
Given PO
• Oxaliplatin
Given IV

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Stephenson Oklahoma Cancer Center at the University of Oklahoma Health Science Center	Oklahoma City	Oklahoma

Sponsors (2)

Lead Sponsor	Collaborator
Roswell Park Cancer Institute	National Comprehensive Cancer Network

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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.