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

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ClinicalTrials.gov Identifier: NCT04097028
Recruitment Status : Not yet recruiting
First Posted : September 20, 2019
Last Update Posted : October 16, 2019
Sponsor:
Collaborators:
National Cancer Institute (NCI)
National Comprehensive Cancer Network
Information provided by (Responsible Party):
Roswell Park Cancer Institute

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.

Condition or disease Intervention/treatment Phase
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 Drug: Trifluridine and Tipiracil Hydrochloride Drug: Oxaliplatin Phase 2

Detailed Description:

PRIMARY OBJECTIVE:

I. 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:

I. Evaluate the 2-year disease-free survival (DFS) and the 2-year overall survival (OS).

II. To determinate the safety and tolerability of induction chemotherapy with trifluridine/tipiracil (FTD/TPI) and oxaliplatin followed by standard chemoradiation and surgery.

EXPLORATORY OBJECTIVE:

I. 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Use of Trifluridine/Tipiracil and Oxaliplatin as Induction Chemotherapy in Resectable Esophageal and Gastroesophageal Junction (GEJ) Adenocarcinoma
Estimated Study Start Date : December 1, 2019
Estimated Primary Completion Date : June 27, 2021
Estimated Study Completion Date : June 27, 2022

Resource links provided by the National Library of Medicine


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: Trifluridine and Tipiracil Hydrochloride
Given PO
Other Names:
  • 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

Drug: Oxaliplatin
Given IV
Other Names:
  • 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




Primary Outcome Measures :
  1. Pathologic complete response rate [ Time Frame: Up to 3 years ]
    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 :
  1. Progression free survival rate [ Time Frame: Time from treatment until disease progression, death from disease, or last follow-up, assessed up to 2 years ]
    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.

  2. Overall survival [ Time Frame: Time from treatment until death due to any cause or last follow-up, assessed up to 2 years ]
    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

  3. Incidence of adverse events [ Time Frame: Up to 30 days after last dose of study drug ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • Other malignancy within the last three years (except for basal cell carcinoma or a noninvasive/in situ cervical cancer)
  • 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 FTD/TPI or history of allergic reactions attributed to compounds of similar composition to FTD/TPI 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04097028


Contacts
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Contact: Ask Roswell 1-800-767-9355 Askroswell@roswellpark.org

Sponsors and Collaborators
Roswell Park Cancer Institute
National Cancer Institute (NCI)
National Comprehensive Cancer Network
Investigators
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Principal Investigator: Sarbjit Mukherjee, MD Roswell Park Cancer Institute

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Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT04097028     History of Changes
Other Study ID Numbers: I 443819
First Posted: September 20, 2019    Key Record Dates
Last Update Posted: October 16, 2019
Last Verified: October 2019

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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
Additional relevant MeSH terms:
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Adenocarcinoma
Esophageal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Trifluridine
Oxaliplatin
Antineoplastic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents