Clinical Trials /

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

NCT04097028

Description:

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.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Esophageal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: I 443819
  • NCT ID: NCT04097028

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

Interventions

DrugSynonymsArms
Trifluridine and Tipiracil Hydrochloride733030-01-8, 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/TipiracilTreatment (TAS-102, oxaliplatin)
Oxaliplatin1-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 oxalatoplatinumTreatment (TAS-102, oxaliplatin)

Purpose

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 cell-free 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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (TAS-102, oxaliplatin)ExperimentalPatients 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.
  • Trifluridine and Tipiracil Hydrochloride
  • Oxaliplatin

Eligibility Criteria

        Inclusion Criteria:

          -  Must have histologically proven loco-regional esophageal or gastroesophageal junction
             adenocarcinoma

          -  Endoscopic ultrasound (EUS) determined node-positive disease with any T-stage or
             T3-T4a with any N stage: Patients with EUS T1N0, T2N0, 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 or legal representative 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
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pathologic complete response rate
Time Frame:Up to 3 years
Safety Issue:
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.

Secondary Outcome Measures

Measure:Progression free survival rate
Time Frame:Time from treatment until disease progression, death from disease, or last follow-up, assessed up to 2 years
Safety Issue:
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.
Measure:Overall survival
Time Frame:Time from treatment until death due to any cause or last follow-up, assessed up to 2 years
Safety Issue:
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
Measure:Incidence of adverse events
Time Frame:Up to 30 days after last dose of study drug
Safety Issue:
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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Roswell Park Cancer Institute

Last Updated

June 12, 2020